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https://f1000research.com/articles/13-887/v1
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05 Aug 24
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{
"type": "Research Article",
"title": "A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19",
"authors": [
"Lantarima Bhoopat",
"Anastasia Martynova",
"April Choi",
"Pattharawin Pattharanitima",
"Semi Han",
"Senxi Du",
"Ibrahim Syed",
"Catherine Chan",
"Esther E Oh",
"Zea Borok",
"Janice Liebler",
"Melissa Lee Wilson",
"Pichaya Tantiyavarong",
"Casey O Connell",
"Anastasia Martynova",
"April Choi",
"Pattharawin Pattharanitima",
"Semi Han",
"Senxi Du",
"Ibrahim Syed",
"Catherine Chan",
"Esther E Oh",
"Zea Borok",
"Janice Liebler",
"Melissa Lee Wilson",
"Pichaya Tantiyavarong",
"Casey O Connell"
],
"abstract": "Background COVID-19 pandemics increases venous thromboembolism (VTE) risk during hospitalization, despite prophylactic anticoagulation. Limited radiological diagnosis in pandemic requires a guided protocol for anticoagulant adjustment.\n\nMethods This retrospective cohort study was conducted at a single center as part of a quality improvement program evaluating the efficacy and safety of anticoagulation protocols. The study focused on implementing a guideline for anticoagulant dosing protocol based on dynamic changes in D-dimer levels in COVID-19 hospitalized patients. The dosing guideline allowed for dose escalation from standard prophylactic levels to escalated prophylactic or therapeutic levels, depending on the patient's risk profile for VTE. The primary endpoints included in-hospital survival comparing between fix and dynamic adjustment treatment groups. Secondary endpoints encompassed major and clinically relevant non-major bleeding (CRNMB) events, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration.\n\nFindings Among the 260 COVID-19-infected patients hospitalized between March 15th and June 15th, 2020. The patients received fixed anticoagulant dosage in 188, 72.3%) patients, while 72 (27.7%) were up-titrated according to the protocol. In-hospital survival at 30 days demonstrated superiority among patients whose anticoagulation was up-titrated to either escalated prophylactic or therapeutic (80.2%) compared to receiving fixed anticoagulant dosage (51.3%) (p=0.01). Bleeding events were significantly higher in up-titrate group (12.5%) compared to fixed anticoagulant dosage group (2.13%). Most of them are CRNMB.\n\nConclusion A dynamic, D-dimer-based dose escalation of anticoagulation for hospitalized patients with COVID-19 holds promise in improving in-hospital mortality rates without a significant increase in fatal bleeding events.",
"keywords": [
"D-dimer",
"Thromboprophylaxis",
"COVID-19"
],
"content": "Introduction\n\nSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID) has resulted in significant morbidity and mortality worldwide. One important mechanism for its adverse impact appears to be its promotion of arterial and venous thrombosis, endothelial dysfunction and enhanced angiogenesis, particularly in the lungs.1 Early data from China found an association between D-dimer and mortality, but the actual incidence of thrombotic events was not reported.2 A subsequent study showed that heparin or low molecular weight heparin (LMWH) improved survival in patients with sepsis-induced coagulopathy (SIC) score ≥ 4 or D-dimer value greater than 6 times the upper limit of normal (ULN).3 However, despite standard heparin or LMWH thromboprophylaxis, the cumulative incidence of thrombotic events in COVID-infected patients stay high almost 50% over critically ill patients in an intensive care unit (ICU) in the Netherlands.4,5 While the recent guidelines support the use of standard thromboprophylaxis in critically ill COVID-19 patients over therapeutic dose anticoagulant in term of survival benefit and days of organ support. However, the use of therapeutic dose heparin in noncritically ill COVID-19 patients reduce the need for mechanical ventilation and improve survival.6\n\nThe concern for breakthrough thrombosis in hospitalized patients with limitations on radiologic testing access, prompted interest in using laboratory-based guide to anticoagulant dose adjustment at our large metropolitan public hospital. A large retrospective cohort shows a cut-off d-dimer of 1.8 mcg/ml FEU with 70% accuracy in diagnosis of acute symptomatic pulmonary embolism (PE) patients that are associated with worse mortality and morbidity outcomes.7 A large retrospective study proposes the D-dimer cut-off of 2495 ng/ml (4.9 mcg/ml FEU) for diagnosis of asymptomatic PE in COVID-19 patients.8 A systematic review also shows an association between D-dimer levels between 1000-4800 microgram/L (2-9.6 mcg/ml FEU) and pulmonary embolism in patients with COVID-19.9\n\nBased on COVID-related limitation on access to radiologic testing for deep vein thrombosis (DVT) and pulmonary embolism (PE) early in the epidemic, we implemented a D-dimer-stratified anticoagulation protocol for COVID patients as part of a quality improvement protocol for hospitalized patients who need anticoagulant. This protocol is dynamic and adjusted in associated with clinical of the patients and d-dimer level. The primary endpoint was in-hospital survival of who received anticoagulant titration according to the protocol compared with those who received fix anticoagulant dose since the beginning. Secondary endpoints included safety outcome, incidence of breakthrough thrombosis, length of hospitalization and ICU stay, days of mechanical ventilator use, and survival duration.\n\n\nMethods\n\nThis single-center retrospective cohort study is part of an ongoing quality improvement initiative evaluating the use of an anti-factor Xa-driven heparin protocol, which includes a low-dose intravenous (IV) unfractionated heparin (UFH) option. A guideline for the use of anticoagulation in COVID-infected patients was implemented in February 2020 to standardize the management of these patients (Figure 1). The inclusion criteria include all patients admitted with COVID-19 pneumonia confirmed by PCR testing between March 15th and June 15th, 2020. Patients who required therapeutic anticoagulation for other indications at the time of admission, those who presented with radiographically confirmed DVT or PE and those who died within 24 hours of anticoagulant treatment were excluded from this analysis. Baseline D-dimer level was obtained on admission and every 24-48 hours during hospitalization. Levels of D-dimer were measured by means of the STA® - Liatest® D-Di Plus assay (Roche Diagnostics SpA, Milan), an immuno-turbidimetric assay for the quantitative determination of D-dimer in venous plasma. Those who presented with radiographically confirmed DVT or PE were started on treatment dose anticoagulation as per the hospital protocol and were therefore excluded from this analysis. Those without existing thrombosis were stratified into two groups based on their D-dimer: those with a D-dimer below 6 mcg/ml FEU (3.0 ug/mL) were given standard prophylactic anticoagulation and those with a D-dimer above this cutoff received escalated prophylactic dosing (LMWH 0.5 mg/kg subcutaneous every 12 hours or low dose heparin intravenous continuous drip titrated to an anti-Xa level of 0.1-0.3). Subsequent dosing increases were made based on a rise in D-dimer to above 6 mcg/mL FEU, an increase of more than 2 mcg/mL FEU/mL despite >48 hours of prophylactic anticoagulation or inability to dialyze due to clotting in line, filter, or machine. Patients who demonstrated acute respiratory decompensation while receiving prophylactic or escalated prophylactic dosing had further escalation to full therapeutic dosing.\n\nBased on our hospital’s anticoagulation protocol (Figure 1), we categorized anticoagulant use as follows:\n\nStandard Prophylactic which includes subcutaneous UFH 5,000 units every 8 hours (if creatinine clearance <30 mL/min), or subcutaneous LMWH with enoxaparin 40 mg once daily (40 mg twice daily if BMI>30; 30 mg once daily if Creatinine Clearance <30 mL/min)\n\nEscalated Prophylactic which includes low-dose IV UFH titrated to achieve an anti-factor Xa level of 0.1-0.3 anti-Xa units (if creatinine clearance <30 mL/min) or enoxaparin 0.5 mg per kilogram body weight subcutaneously every 12 hours (if creatinine clearance ≥ 30 mL/min)\n\nStandard Therapeutic dose used, which includes therapeutic dose IV UFH titrated to achieve an anti-factor Xa level of 0.3-0.7 anti-Xa units, or enoxaparin 1 mg per kilogram body weight every 12 hours during the hospitalization.\n\nPatients treated with different anticoagulation regimens during their hospitalization were categorized into 2 categories based on their requirement of dosing up-titration as who received up-titrating according to the protocol and who received fixed anticoagulant dosing. (Figure 1)\n\nWe collected baseline demographic data including age, sex, body mass index (BMI), ethnicity, comorbidities, baseline inflammatory markers, and clinical parameters associated with disease severity including intensive care unit (ICU) admission, requirement for high flow nasal cannula (HFNC), mechanical ventilation (MV), use of vasopressor for maintenance of hemodynamic stability, and sepsis-induced coagulopathy score (SICS)10 and also COVID-specific therapies.\n\nThe primary endpoints assessed were 30 day-in-hospital survival based on patients who were titrated to either escalated or therapeutic dose compared to fixed dose anticoagulant. We also adjust the potential covariates factors that affect in-hospital survival, such as D-dimer levels, age, ethnicity, BMI, comorbidities, ICU admission, mechanical ventilation, HFNC, SIC score, COVID treatment, thrombosis, and bleeding events. Secondary end points included bleeding outcome according to International Society on Thrombosis and Hemostasis (ISTH) defined major and clinically relevant non-major bleeding events.11 Breakthrough thrombosis was recorded if identified on a radiologic study (venous duplex ultrasonography, CT-pulmonary angiogram, CT with contrast, CT or MRI brain) during the course of the hospital stay. Duration of hospitalization and ICU stay, and days of mechanical ventilator use.\n\nTo compare demographic data among treatment groups, ANOVA or Kruskal-Wallis were used for continuous data, and Pearson’s Chi-Squared or Fisher’s exact test for categorical data. The bleeding outcomes among the groups were compared using exact probability tests without p-value adjustment for multiplicity. Dichotomous secondary outcomes were assessed using univariate logistic regression. In-hospital survival stratified by treatment groups was tested using Log rank testing and visualized using Kaplan Meier estimates. The Cox proportional hazard model was used to identify potential predictive factors for in-hospital mortality. We evaluated the following potential covariates: D-dimer levels, age, ethnicity, BMI, comorbidities, ICU admission, mechanical ventilation, HFNC, SIC score, COVID treatment, thrombosis, and bleeding events. Variables were included in the model if they were either predictors or confounders, defined as any variable that alters the effect size by >15% when included in the model. Scale Schoenfeld residuals were tested in the final model and showed a valid proportional hazard assumption. All analyses were performed by STATA SE 17.0(Stata Corp, College Station, TX). We present 95% confidence interval of any effect measures with two-sided p value of 0.05 for statistical significance. This study is reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology statement for observational studies.\n\nAccording to COVID infection was a new emerging disease at the time of the study conducted, all eligible patients meeting inclusion criteria were included in the study. However, 2 patients had missing data on the primary outcome and were subsequently excluded from the analysis. Power was calculated retrospectively using STATA SE 17.0 revealing power of 0.99 at an alpha error (significant) threshold of 0.05STATA SE 17.0 used for all statistical analysis is licensed to the Faculty of Medicine, Thammasat University. RStudio, An open-access alternative software capable of performing equivalent functions for statistical analysis, is available for download at https://posit.co/download/rstudio-desktop/.\n\nFormulae\n\nThe syntax for calculating power for two proportions in Stata is:\n\np1 and p2: The proportions of the two groups you are comparing.\n\nalpha: The significance level\n\npower: The desired power of the test\n\nn1 and n2: The sample sizes for the two groups.\n\ntesttype: The type of test to conduct (e.g., two-sided or one-sided).\n\n. power twoproportions 0.802 0.513, test (chi2) n1(72) n2(188)\n\nEstimated power for a two-sample proportions test\n\nPearson's chi-squared test\n\nH0: p2 = p1 versus Ha: p2 != p1\n\nStudy parameters: alpha = 0.0500\n\nN = 260\n\nN1 = 72\n\nN2 = 188\n\nN2/N1 = 2.6111\n\ndelta = -0.2890 (difference)\n\np1 = 0.8020\n\np2 = 0.5130\n\nEstimated power: power = 0.9956\n\n\nResults\n\nThe cohort comprised 260 hospitalized COVID-infected patients, with 137 of them being male (72.9%). The initial anticoagulant dosage was categorized as prophylactic for 242 patients (93.1%), escalated prophylactic for 6 patients (2.3%), and therapeutic for 12 patients (4.6%). Most patients (188, 72.3%) received a fixed anticoagulant dosage throughout their hospital stay. Among those receiving fixed anticoagulant dosing, they were further classified into fixed prophylactic dosing (171, 90.9%), fixed escalated prophylactic dosing (6, 3.2%), and fixed therapeutic dosing (11, 5.85%) treatment. There were 72 (27.7%) patients who had their anticoagulant doses adjusted to either escalated or therapeutic doses over the course of hospital stay based on their D-dimer trend. (Table 1). The patients in the anticoagulant adjustment group were significantly older than the patients in the fixed prophylactic group (mean age 60.7 ± 12.2 vs 54.6 ± 15.9 years, p<0.01). Most of the patients (178, 68.4%) had comorbidities that were associated with higher thrombotic risk. The most common thrombotic risk is cardiovascular risk factors.\n\na Continuous variables are presented as means and standard deviations (SD) or median with minimum and maximum, while categorical variables are presented as counts and percentages.\n\nb P-values were obtained using one-way ANOVA for continuous variables and Pearson’s Chi-Squared or Fisher’s Exact Test for categorical variables, as appropriate.\n\n* Statistically significant difference compared to prophylactic at p<0.05 with Bonferroni p-value correction (ANOVA).\n\nThe patients who were treated with anticoagulant adjustment received more aggressive treatment for COVID infection such as remdesivir, azithromycin, hydroxychloroquine, convalescent plasma, and steroid according to their severe clinical course, while 40.4% of the patients who received fixed anticoagulant group received only supportive treatment. The severity of patients in anticoagulant adjustment groups were referred to a higher rates of ICU admission (86.1%), higher rate of high flow nasal cannula (HFNC) requirement (69.4%), higher rate of mechanical ventilator (MV) requirement (66.7%) and higher rate of vasopressor use (53.5%) compared to fixed anticoagulant group. The sepsis induced coagulopathy scores (SICS) were also significantly higher in this group (53.5%), correlated with higher lactate dehydrogenase (LDH), d-dimer level at baseline and at peak amount during admission as shown in Table 1.\n\nThe mortality rate in this cohort of hospitalized COVID-infected patients was 12.7%. When we compared 30 days in-hospital survival of the patients who received anticoagulant adjustment (up-titrating) according to the protocol to whom that received fixed anticoagulant dosing, the up-titrated group showed statistically significantly higher in-hospital survival until discharge at 30 days of 80.2% compared to 51.3 % in the fixed anticoagulant group. (Figure 2)\n\nBased on the multivariable Cox regression, we found factors that independently increased in-hospital mortality that include increasing age (HR 1.05, 95%CI:1.02,1.08), azithromycin treatment (HR 5.80, 95%CI:1.29, 25.97). Lower in-hospital mortality was associated with steroid treatment (HR 0.39, 95%CI:0.16, 0.96). We found that receiving up-titrated heparin was an independent factor associated with lower in-hospital mortality. (HR 0.31, 95%CI:0.13, 0.75).\n\nThe median hospitalization time was 5 days among all patients, ranging from 1 to 80 days. Those who underwent anticoagulant adjustment experienced more severe clinical conditions. Most of them required intensive care unit (ICU) admission (86.1%) and the use of mechanical ventilation (MV) (66.7%). In contrast, the group with fixed anticoagulant treatment had less severe clinical conditions and a shorter hospitalization duration, with a median stay of 4 days, compared to 21 days in the anticoagulant adjustment group.\n\nThe median duration of ICU stay was 7 days for all patients. Patients who received anticoagulant adjustments had significantly longer ICU stays and mechanical ventilation durations when compared to those on fixed anticoagulant treatment. Specifically, in the fixed anticoagulant group, the median ICU stay was 3 days, whereas in the anticoagulant adjustment group extended to 18 days. (p<0.001) Similarly, the median duration of mechanical ventilation use was 10 days in the fixed anticoagulant group, compared to 19 days in the anticoagulant adjustment group. (p<0.001) However, among the patients who died in the hospital. The patients who received anticoagulant adjustment had a longer survival duration, with a median of 22.5 days (ranging from 11 to 68 days), compared to 8.5 days (ranging from 1 to 27 days) in the fixed anticoagulant group.\n\nAcross the cohort, there were 13 patients who experienced bleeding events (5%). Only one major bleeding event (0.38%) occurred in up-titrate anticoagulant group, while 12 patients (4.62%) experienced clinically relevant non-major bleeding (CRNMB) event by ISTH criteria. The prevalence of all type of bleedings were significantly higher in patients who received anticoagulant adjustment compared to who received fixed anticoagulant dosage (12.5% vs 2.13%, p<0.01). There were 7 patients (2.7%) who experienced breakthrough thrombosis. Six patients in the anticoagulant adjustment group developed venous thromboembolism (VTE), while one of the patients in fixed anticoagulant group developed arterial thrombosis. The only arterial thrombotic event that developed in fixed anticoagulant group is an ischemic stroke, and common thrombotic event in anticoagulant adjustment group was deep vein thrombosis (DVT).\n\n\nDiscussion\n\nMany reports and observational studies early in the COVID pandemic era suggest a survival benefit for use of anticoagulation among severely ill COVID patients.2–4 Considering this, we assessed a quality improvement initiative aimed at implementing a D-dimer-guided anticoagulation strategy for COVID-infected inpatients. We chose a D-dimer-based strategy due to the limited availability of radiologic studies during the COVID-19 pandemic. The most recent guidelines support the use of regular thromboprophylaxis for severely ill COVID-19 patients, as starting with therapeutic-dose heparin as an initial approach did not improve the chances of survival until hospital discharge or having more days without requiring cardiovascular or respiratory organ support.12 On the other hand, the use of therapeutic-dose heparin in non-severely ill COVID-19 patients reduces the need for mechanical ventilation and improves overall survival.6 Our strategy was dynamically adjusted upon the patient’s condition and d-dimer. We stratified patients into three groups, based on D-dimer level on admission and followed a stepwise up-titration of anticoagulation based on D-dimer values, which could occur at any time during the hospitalization. We found that there was no survival benefit for 6 patients who received a fixed therapeutic dose from the beginning of their hospitalization when compared to those who were up-titrated later in their hospital course. This suggests that the dynamic adjustment of anticoagulation treatment yields better survival outcomes compared to a fixed anticoagulant dose, whether it was fixed prophylactic or fixed therapeutic anticoagulation. We observed a suppression of D-dimer values within the first week of using higher doses of anticoagulation, suggesting that up-titrating anticoagulation may mitigate the expected adverse impact on survival.\n\nThe prevalence of bleeding events was higher in the patients who received up-titrate doses of anticoagulation. The one major bleeding event observed was due to esophageal varices in a patient with previously undiagnosed liver cirrhosis, while others are clinically relevant non-major bleeding (CRNMB) that managed with standard supportive care and bleeding was not independently associated with survival outcome. The overall incidence of breakthrough thrombotic events was 2.7%, but this is likely underestimated due to a limited number of diagnostic studies performed in era of new emerging COVID disease.\n\nThe strengths of our D-dimer-titrated anticoagulation strategy included the use of a simple diagnostic test to stratify patient risk and allow for a dynamic reassessment over the course of the hospitalization. Using the rise in D- dimer as a trigger to increase anticoagulant allowed us to intervene early in the disease course. Our study is limited by its retrospective nature and lack of uniform diagnostic evaluation for DVT/PE in COVID-infected patients, even in those with suggestive symptoms. Previously, Demelo-Rodriguez et al reported that 15% of patients with COVID and elevated D-dimer levels have asymptomatic DVT.13 COVID infection is notably associated with a high risk of thrombotic complications, even in anticoagulated patients; therefore, the number of VTE reported in our cohort is likely underestimated. Furthermore, we did not collect data regarding thrombotic events that might have occurred after patients were discharged, and no autopsies were performed at our site to confirm the causes of death. Finally, we did not include a de-escalation strategy in our guideline, so this was done inconsistently based on physician discretion.\n\nIn this quality improvement evaluation of a D-dimer-titrated anticoagulation strategy for hospitalized patients with COVID, we found that D-dimer combined with clinically-driven anticoagulation adjustment was associated with reduced in-hospital mortality with a manageable increase in minor bleeding events.\n\n\nConsent to participate\n\nInformed consent waiver was obtained by University of Southern California Institutional Review Board. Based on the U.S. Code of Federal Regulations (CFR), the IRB determined that this study was exempt from 45 CFR 46 according to §46.104(d) as category 4 – Exempt Research as follows:\n\n“(4) Secondary research for which consent is not required: Secondary research uses of identifiable private information or identifiable biospecimens, if at least one of the following criteria is met:\n\n(i) The identifiable private information or identifiable biospecimens are publicly available;\n\n(ii) Information, which may include information about biospecimens, is recorded by the investigator in such a manner that the identity of the human subjects cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects;\n\n(iii) The research involves only information collection and analysis involving the investigator’s use of identifiable health information when that use is regulated under 45 CFR parts 160 and 164, subparts A and E, for the purposes of \"health care operations\" or \"research\" as those terms are defined at 45CFR 164.501 or for \"public health activities and purposes\" as described under 45 CFR 164.512(b);\n\n(iv) The research is conducted by, or on behalf of, a Federal department or agency using government-generated or government-collected information obtained for non research activities, ift he research generates identifiable private information that is or will be maintained on information technology that is subject to and in compliance with section 208(b) of the E-Government Act of2002, 44 U.S.C. 3501 note, if all of the identifiable private information collected, used, or generated as part of the activity will be maintained in systems of records subject to the Privacy Act of 1974, 5U.S.C. 552a, and, if applicable, the information used in the research was collected subject to the Paperwork Reduction Act of 1995, 44 U.S.C. 3501 et seq.”\n\nEthical approval: Based on the review conducted by the University of Southern California Institutional Review Board (IRB) designee on April 13, 2021, the study has been evaluated and categorized as exempt. The study is authorized to proceed with conducting as approved by the IRB. This exemption indicates that the research poses minimal risk to participants or involves only the collection of existing data, among other criteria outlined in the regulations\n\n\nAuthor contribution statement\n\n\n\n1. Lantarima Bhoopat performed study design, investigation, data curation, formal analysis, data interpretation, writing - original draft, writing - review & editing.\n\n2. Anastasia Martynova performed investigation, data curation, data interpretation, writing- original draft, writing - review & editing.\n\n3. April Choi performed investigation, data curation, writing – original draft, writing -review & editing.\n\n4. Pattharawin Pattharanitima performed formal analysis, review & editing.\n\n5. Semi Han performed Data acquisition, review & editing.\n\n6. Senxi Du performed data abstraction, review & editing.\n\n7. Ibrahim Syed performed data curation, review & editing.\n\n8. Catherine Chan performed data curation, review & editing.\n\n9. Esther E Oh performed data curation, investigation, review & editing.\n\n10. Zea Borok performed conceptualization, review and editing.\n\n11. Janice Liebler performed conceptualization, review and editing.\n\n12. Melissa Lee Wilson performed data analysis and interpretation, drafting statistical methods section, writing- review and editing.\n\n13. Pichaya Tantiyavarong performed data analysis, data interpretation, writing-review & editing.\n\n14. Casey O’Connell performed conceptualization, project administration, supervision, validation, writing – review & editing.",
"appendix": "Data availability\n\nZenodo: A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19, https://doi.org/10.5281/zenodo.12626945. 14\n\nThe project contains the following underlying data covidheparin_deidentified.xls.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\nZenodo: STROBE checklist for A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19. Zenodo. https://doi.org/10.5281/zenodo.12730540. 15\n\nThe project contains the following underlying data\n\nSTROBE_checklist-ddCOVID.pdf\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nDataset available at https://doi.org/10.5281/zenodo.10649845\n\n\nReference\n\nRapkiewicz AV, Mai X, Carsons SE, et al.: Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series. EClinicalMedicine. 2020; 24: 100434. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhou F, Yu T, Du R, et al.: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229): 1054–1062. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTang N, Bai H, Chen X, et al.: Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J. Thromb. Haemost. 2020; 18(5): 1094–1099. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlok FA, Kruip M, van der Meer NJM , et al.: Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb. Res. 2020; 191: 145–147. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHelms J, Tacquard C, Severac F, et al.: High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46(6): 1089–1098. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLawler PR, Goligher EC, Berger JS, et al.: Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N. Engl. J. Med. 2021; 385(9): 790–802. PubMed Abstract | Publisher Full Text\n\nGul MH, Htun ZM, de Jesus PV , et al.: Predictors and outcomes of acute pulmonary embolism in COVID-19; insights from US National COVID cohort collaborative. Respir. Res. 2023; 24(1): 59. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNadeem I, Anwar A, Jordon L, et al.: Relationship of D-dimer and prediction of pulmonary embolism in hospitalized COVID-19 patients: a multicenter study. Future Microbiol. 2021; 16(12): 863–870. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKwee RM, Adams HJA, Kwee TC: Pulmonary embolism in patients with COVID-19 and value of D-dimer assessment: a meta-analysis. Eur. Radiol. 2021; 31(11): 8168–8186. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIba T, Nisio MD, Levy JH, et al.: New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017; 7(9): e017046. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaatz S, Ahmad D, Spyropoulos AC, et al.: Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. J. Thromb. Haemost. 2015; 13(11): 2119–2126. PubMed Abstract | Publisher Full Text\n\nGoligher EC, Bradbury CA, McVerry BJ, et al.: Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N. Engl. J. Med. 2021; 385(9): 777–789. PubMed Abstract | Publisher Full Text\n\nDemelo-Rodríguez P, Cervilla-Muñoz E, Ordieres-Ortega L, et al.: Incidence of asymptomatic deep vein thrombosis in patients with COVID-19 pneumonia and elevated D-dimer levels. Thromb. Res. 2020; 192: 23–26. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhoopat L: A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19. [Data set]. Zenodo. 2024. Publisher Full Text\n\nBhoopat L: STROBE checklist for A Dynamic, D-dimer-based Thromboprophylaxis Strategy in Patients with COVID-19. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "311489",
"date": "19 Aug 2024",
"name": "Prof. NOPPACHARN UAPRASERT",
"expertise": [
"Reviewer Expertise Thrombosis and Hemostasis"
],
"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 conducted a retrospective study to compare the survival benefit between fixed and up-titrated anticoagulation guided by D-dimer levels. The findings of this study are very interesting and may guide anticoagulation for hospitalized COVID-19 patients. However, there are several concerns that need to be addressed.\n\n1. Patients should be classified as mild, moderate, severe, or critical according to standard guidelines, as mortality is likely to be associated with their severity. 2. Dynamic changes in D-dimer levels in both groups during hospitalization should be demonstrated in the results section. 3. It is apparent that patients receiving up-titrated anticoagulants had greater severity, received more intensive treatment (including steroids), and had a longer ICU stay. How did the authors explain the lower mortality in more severe COVID-19 patients? 4. Were the D-dimer levels suppressed after escalated doses of anticoagulants? Was the suppression of D-dimer associated with survival? The authors should demonstrate the results if available and address this in the discussion. 5. Due to the small sample size in the up-titrated group, it is very difficult to make a definitive association in multivariate analysis. For example, the survival benefit of anticoagulation may depend on steroids. Therefore, this limitation needs to be clearly addressed.\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? No source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12321",
"date": "04 Sep 2024",
"name": "Lantarima Bhoopat",
"role": "Author Response",
"response": "I would like to thank you the reviewer for the review and comments. I would address the queries as below. 1. Patients should be classified as mild, moderate, severe, or critical according to standard guidelines, as mortality is likely to be associated with their severity. Author Response: When defining COVID-19 severity according to standard guidelines, the severity is classified as mild for those with mild symptoms. Moderate disease is defined by the presence of clinical or radiographic evidence of lower respiratory tract disease but with a blood oxygen saturation of 94% or higher, and it requires hospitalization. Indicators of severe disease include hypoxemia with oxygen saturation ≤93% or a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen <300. Critical illness is defined by respiratory failure requiring mechanical ventilation or shock requiring vasopressors. According to this definition, we found that 50.5% of patients in the fixed-dose group had severe disease, compared to 20.8% in the up-titrate group. Additionally, there were more critical patients in the up-titrate group, with 47.2% compared to 6.4% in the fixed-dose population. After reclassifying the patients according to standard guidelines, the combination of severe and critical patients accounts for more than half of both groups. 2. Dynamic changes in D-dimer levels in both groups during hospitalization should be demonstrated in the results section. Author Response: We added D-dimer analysis section as reviewer suggests. Mean profiles over time of D-dimer levels during hospitalization in both groups are shown in Figure 3A. The timing of D-dimer level progression varied among patients. Thus, we also compared and graphically presented the mean profiles over time of D-dimer after each escalation step using a random-intercept linear mixed model, as shown in Figure 3C. The peak effect of escalated and therapeutic heparin on D-dimer levels clearly occurred within the first week of each escalation step and might affect outcomes in the up-titrate group that will address in the 4th question. Please refer to Figure 3A here -https://f1000research.s3.amazonaws.com/linked/672277.146710_Figure_3A.pdf Figure 3A: Mean profiles of D-dimer over hospitalization days 3. It is apparent that patients receiving up-titrated anticoagulants had greater severity, received more intensive treatment (including steroids), and had a longer ICU stay. How did the authors explain the lower mortality in more severe COVID-19 patients? Author Response: After reclassifying the patients according to standard guidelines, the combination of severe and critical patients accounts for more than half of both groups. The d-dimer analysis shows an insuppressible trend among the deceased, which might explain the worse outcomes in this population. These patients might require early titration of anticoagulants, additional treatment options, or a combination of both. We will add on this information in the discussion section. 4. Were the D-dimer levels suppressed after escalated doses of anticoagulants? Was the suppression of D-dimer associated with survival? The authors should demonstrate the results if available and address this in the discussion. Author Response: When comparing the mean D-dimer level trends between patients who survived and those who died, we found a higher trend among the deceased, particularly during the first week of hospitalization for patients who received a fixed-dose anticoagulant. The progression of D-dimer levels in patients who died while receiving an up-titrated anticoagulant occurred after the first week, as shown in Figure 3B. The suppressible level of D-dimer might explain the survival advantage of the up-titrated group in the early course of the disease. Considering the different timing of D-dimer progression in each patient, we also compared and graphically presented the mean profiles over time of D-dimer levels after each escalation step using a random-intercept linear mixed model, as shown in Figure 3C. This model accounted for the correlation of D-dimer measurements within individuals. The fixed effects included time measuring D-dimer, treatment groups, and the interaction of these variables. A restricted cubic spline with 3 degrees of freedom was applied to relax the linearity assumption. The peak effect of escalated and therapeutic heparin on D-dimer levels clearly occurred within the first week of each escalation treatment (as shown in Figure 3C). However, a peak D-dimer level above or equal to 6 mcg/ml FEU (3.0 ug/mL) or below 6 FEU/ml (3.0 ug/mL) was not associated with survival outcome nor was it a confounder; therefore, it was not included in the survival model. Please refer to Figure 3B here -https://f1000research.s3.amazonaws.com/linked/672278.146710_Figure_3B.pdf Figure 3B: Mean profiles over time of D-dimer according to survival outcome and anticoagulant group. Please refer to Figure 3C here -https://f1000research.s3.amazonaws.com/linked/672279.146710_Figure_3C.pdf Figure 3C: Mean profiles over time of D-dimer for each escalated step by random-intercept linear mixed model 5. Due to the small sample size in the up-titrated group, it is very difficult to make a definitive association in multivariate analysis. For example, the survival benefit of anticoagulation may depend on steroids. Therefore, this limitation needs to be clearly addressed. Author Response: Upon the reviewer suggested, we added information in survival outcome section to address that limitation as in the Cox proportional hazards model, Schoenfeld residuals were tested in the final model, the results showed that the proportional hazards assumption was valid, allowing us to interpret the independent effect of the up-titrated group separate from the effect of steroids."
},
{
"c_id": "12683",
"date": "22 Oct 2024",
"name": "Lantarima Bhoopat",
"role": "Author Response",
"response": "I re-analyzed the data today and found some mistakes in the numbers after reclassification according to the standard guidelines that I addressed in my response to the reviewer's first question in paragraph 2. I would like to correct them as follows. According to this definition, we found that 40.9 % of patients in the fixed-dose group had severe disease, compared to 15.3% in the up-titrate group. Additionally, there were more critical patients in the up-titrate group, with 72.2% compared to 18.1% in the fixed-dose population. After reclassifying the patients according to standard guidelines, the combination of severe and critical patients accounts for more than half of both groups."
}
]
}
] | 1
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https://f1000research.com/articles/13-887
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https://f1000research.com/articles/12-1381/v1
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20 Oct 23
|
{
"type": "Research Article",
"title": "Navigating techno-stress: A qualitative exploration of university faculty's experiences and perspectives in the Peruvian context amidst the return to classes and the post-COVID-19 era",
"authors": [
"Josefina Amanda Suyo-Vega",
"Monica Elisa Meneses-La-Riva",
"Víctor Hugo Fernández-Bedoya"
],
"abstract": "Background: Technology serves as a potent tool that enhances the quality of teaching and learning experiences. However, when educators lack proficiency in utilizing technology, it leads to obstacles in providing effective education, resulting in emotions of frustration, diminished self-assurance, and uncertainty regarding their teaching abilities. This study aims to investigate the experiences of university faculty members in relation to the impact of technology on their mental well-being. Methods: For this qualitative study, ten professionals engaged in university-level teaching, encompassing research domains, were selected for interviews. Inclusion criteria were based on teaching experience, tenure, specific courses or subjects taught, and active involvement during the research phase. The guiding question for the study was framed as follows: \"What are the experiences and perceptions of university faculty members concerning techno-stress?\" Additionally, the study identified four subcategories: work overload, social and emotional interaction, adaption to new technologies, and expectations and teaching quality. Results: Techno-stress is a composite of emotional and physical reactions triggered by the improper use of technology. Faculty members’ encounters with techno-stress have substantial implications for their quality of life. The subcategories shed light on different aspects of the faculty’s experiences, including the burden of excessive workload, the influence of social and emotional interactions, the process of adapting to evolving technologies, and the connection between expectations and the quality of their teaching. Conclusions: This research underscores the significance of technology in higher education, highlighting its potential to positively impact teaching and learning. Nevertheless, faculty members’ struggles with techno-stress indicate a pressing need for effective training and support. Establishing limits on connectivity with technology and others emerges as a crucial step in maintaining a healthy work-life balance. Ultimately, addressing techno-stress and providing appropriate guidance are essential for safeguarding the well-being of university faculty members and, consequently, enhancing the overall educational experience.",
"keywords": [
"Technology",
"Teaching and learning",
"Qualitative study",
"Techno-stress",
"Adapting to technology",
"Work overload",
"Mental well-being"
],
"content": "Introduction\n\nThe digital era brings changes in how teachers teach, and students learn. While technology is a useful tool, it also has negative impacts on the mental health of teachers.\n\nUniversity professors now create and manage more digital content, leading to increased stress and anxiety (Alvites, 2019; Rivadeneira Guerrero et al., 2020). Additionally, in the university setting, professors must continuously update their knowledge on technology-related topics, which generates pressure (Alvites, 2019). Students expect quick responses and constant availability from their professors to address even minor doubts (Suyo-Vega et al., 2022). It is necessary for teachers to establish boundaries on working hours and workload to protect their mental health and well-being. Factors like social isolation, digital fatigue, heavier workloads, and adaptation to new technologies negatively impact the mental health of professors (Abarca et al., 2022; De Lima Santana et al., 2022; Morales-Rodríguez, 2021). Therefore, practical strategies must be implemented to improve their well-being (CEPAL, 2020).\n\nStudies on the incorporation of ICTs in class sessions show that older professors, aged over 45, tend to prefer traditional methods, finding them more satisfying and committing to the teaching process (Genimon Vadakkemulanjanal et al., 2021). In India, research on technostress confirms a negative relationship with technology among different age groups and levels of commitment based on experience and age (Genimon Vadakkemulanjanal et al., 2021). Specifically, technostress is generated by the use of technology in academic activities carried out by teachers (Zheng et al., 2022).\n\nConsidering the impact of the pandemic on the job stress of university professors, researchers emphasize the importance of addressing this issue in higher education to ensure the well-being of teachers. They suggest measures to prevent and reduce the negative impact of stress (Manzur-Vera et al., 2022).\n\nThe technostress or tech stress is caused by work overload and the process of adapting to technologies (Tondeur et al., 2008), affecting the interpersonal relationships of professors with students, colleagues, friends, and family (Maslach et al., 2001; Romero-Martín & Fraile-Aranda, 2017; Torres-Hernández, 2023).\n\nThe literature review on technostress reveals four subcategories that are the focus of this research, based on Maslach’s Burnout theory and Tondeur’s work on the relationship between work and technology.\n\nThe first subcategory, Work Overload, describes the excessive workload and the constant need to be available, answering emails, WhatsApp messages, and engaging in social media interactions. Professors respond to this overload in two ways: some seek help to complete their tasks, while others reject assistance and prefer to handle all activities, despite spending excessive hours in front of a computer. Studies suggest paying attention to technostress and its effects on teachers’ quality of life and work-life balance (Decataldo & Fiore, 2022). Prolonged use of electronic devices and exposure to blue light can affect the physical health of professors, leading to eye fatigue, headaches, and sleep disturbances (Estrada Araoz et al., 2021; Fernández Villacres et al., 2021; Kaya, 2020). It is essential to take care of professors’ physical and cognitive health, as it can impact their attention, concentration, and memory (Corrente et al., 2022; Jimenez, 2021). Therefore, professors must be mindful of using technology effectively and in a balanced manner.\n\nWhile some studies demonstrate the positive impact of Information and Communication Technologies (ICT) on the work experience, they also suggest that appropriate implementation of ICT can reduce demands. Thus, considering individual characteristics and organizational procedures in implementing ICT can improve how teachers interpret their experiences related to ICT and ultimately enhance their performance and well-being at work (Pansini et al., 2023; Sánchez-Macías et al., 2021).\n\nThe second subcategory, Social and Emotional Interaction, deals with how teachers manage and channel emotions in front of students. Focusing on emotions in a digital environment is challenging, as they are complex human characteristics that are difficult to define, recognize, and classify (Francisti et al., 2023). Research emphasizes the importance of social and emotional interaction to avoid negative emotional and behavioral consequences (Simona et al., 2021). Therefore, teachers seek diverse pedagogical methods and practices to strengthen students’ competencies (Zotova et al., 2021). Identifying emotions, sharing feelings, and developing empathy towards others are vital components of the learning process, or at least they aid in it (Ch’ng, 2019; Drewelow, 2020; Wetcho & Na-Songkhla, 2022).\n\nThe third subcategory, Adaptation to New Technologies, describes the experiences of both teachers and students, as the post-pandemic generation faces technological changes from multiple perspectives. Advantages and opportunities arise from the use of technological tools in the teaching process (Bendito Cañizares & Sánchez Botas, 2021; Pribeanu & Gabriel Gorghiu, 2022; Shulga et al., 2021). However, research conducted in Turkey reveals that both teachers and students prefer in-person teaching, as they detected issues with distance learning (Rakhimgalieva et al., 2021).\n\nFinally, the fourth subcategory, Expectations and Teaching Quality, deals with different teaching approaches, some focused-on theory, others on practice, and some aiming to combine both. However, technology plays a role in all cases. Despite two years passing since the pandemic, there is a lack of attention and concrete actions to address teacher technostress, affecting the social, occupational, and psychological aspects (Abarca et al., 2022). The intention is to adapt to technology without harming the mental health of teachers or students, in order to provide quality education, recognizing the potential of ICTs (Sánchez-Macías et al., 2021). The relevance of using tools like Moodle and Facebook is evident as they improve student learning and teaching quality (Delgado-García et al., 2017).\n\nWith regard to gender, there are various research studies related to university students as well as female professors, which show high levels of stress in relation to the male gender (Garcés-Delgado et al., 2023; Mena Freire et al., 2022). These findings highlight the need for in-depth research on technostress in the academic context in order to expand our understanding of the experiences and challenges faced by professionals in teaching.\n\nThe following research question was proposed: How does technostress manifest among university professors, particularly in terms of work overload, challenges in social and emotional interactions, adaptation to new technologies, and changing expectations?\n\nAs there is a need to delve deeper into the topic of technology and its impact on mental health, it is essential to investigate the experiences and perceptions of university professors regarding technostress. This research is relevant as technology becomes more prevalent in education and may be affecting the mental health of teachers, which, in turn, can influence students’ academic success. This investigation aims to offer new knowledge and strengthen existing theories to find solutions to the identified problems.\n\n\nMethods\n\nThe research obtained approval from the ethics committee of the doctoral program at Universidad César Vallejo (N° 00035-2023), visible at: https://doi.org/10.5281/zenodo.8226629.\n\nThe research adopted a qualitative approach and employed the grounded theory method, which enables the researcher to conduct organized and rigorous research (De la Espriella & Gómez Restrepo, 2020; Vives Varela & Hamui Sutton, 2021). This investigation was conducted within the constructivist paradigm, allowing key participants or interviewees to construct their experiences related to a phenomenon (Guba & Lincoln, 1994). In this regard, the research focuses on interpreting how teaching professionals make sense of their experiences with technology.\n\nEight (8) female interviewees and two (2) male interviewees were selected. The choice to interview ten key participants was based on the fact that, for an in-depth interview, a minimum of ten participants is recommended (Hernández-Sampieri & Mendoza Torres, 2018). This decision is grounded in the gender inequality within higher education and research in Peru (Nieto Montesinos et al., 2019). Despite the increased participation of women as full-time professors, their representation in high-level academic roles remains low (UNESCO - IESALC, 2021). The proportion of female researchers is also significantly lower compared to the total number of female professors (Chávez Irigoyen & Penelas Ronso Merino, 2021). The gender distribution in the interviews aims to gain a better understanding of this issue and give voice to the experiences of both women and men in higher education and research.\n\nThe key participants in the research were university teachers with prior and post-pandemic teaching experience. The selection was made among professors from both national and private universities who had more than five years of experience. This restriction was due to the fact that these professionals had engaged in both in-person and virtual teaching activities before and after the pandemic. The chosen university professors taught courses related to research, including seminars, methodology, thesis design, and development. In all cases, these professionals were responsible for reviewing students’ projects and theses, which required dedicating numerous hours to reading and revising each academic product.\n\nFor data collection, verbal informed consent was obtained from the professors, and dates and times for interviews were scheduled. Since each interviewed teacher is located in different regions of Peru, consent was given during the interview sessions, which were recorded. Each interview lasted an average of 31 minutes, during which four important aspects were discussed: (a) Work overload, including technical difficulties and quality expectations. (b) Social and emotional interaction, encompassing physical and mental health issues. (c) Adaptation to new technologies, addressing the challenges of adjusting to emerging technologies. (d) Expectations and teaching quality. These four subcategories were derived from the literature review and are described in Table 1, detailing each statement’s characteristics. Following the interviews, a meeting was held with five researchers from the team to discuss and analyse the interviewees’ responses and establish new subcategories. No specialized software was used for data processing. Finally, the results and conclusions were written, as shown in Figure 1.\n\nTable 1 presents the statements for the interviewees, derived from the subcategories resulting from the analysis of the literature review.\n\nThe second instrument used was the group interview, which derived from the technique of Group Discussion. In the virtual context, a meeting was conducted with five education professionals who discussed the stated positions. The questions were guided as shown in Table 1, as obtaining depth was best achieved by listening to each professional’s viewpoint based on their experience.\n\nFor the application of the instrument, it was analyzed and validated through education professionals. Additionally, it met the criteria of quality (a) Credibility, (b) Transferability, (c) Reliability and Confirmability, and (d) Reflexivity (Korstjens & Moser, 2018).\n\nIn the research process, a meticulous data processing stage was conducted, enabling the management of data in a rigorous and reliable manner. Table 2 describes the strategies and activities carried out in accordance with the established quality criteria. The activities undertaken align with strategies such as interaction with the study subjects, data triangulation, member checking, detailed description, audit trail recording, and journaling.\n\nFor the data analysis stage, a specific methodological approach was followed, allowing for the identification of emerging themes based on responses provided by key participants. The coding of the interviewees and their responses strengthened the identification of subcategories. Tables 4, 5, 6, and 7 provide detailed coding of the interviewees, their responses, and the emerging concepts, which were used to draw conclusions and develop a profound understanding of the techno-stress-related topic. Furthermore, we applied the SAGER guidelines to discern the analysis between individuals of male and female gender (Heidari et al., 2016).\n\nAdditionally, it is important to mention that the emerging concepts are also presented in Figures 2, 3, 4, and 5.\n\n\nResults\n\nThe results were grouped according to the established subcategories.\n\nSome interviewees consider work overload as moderate and high, which, in some cases, led to physical and emotional exhaustion. However, they are committed to providing quality education and rely on technological tools to optimize the teaching processes. University educators are facing various levels of work overload that can affect their physical and mental well-being. Although some can easily handle the changes.\n\nSome interviewees emphasize the importance of emotional connection between teachers and students in order to avoid affecting the teaching process. There is also a need to channel emotions appropriately to carry out the teaching function. This can be achieved through recreational activities, physical activities, or spending time alone. However, one teacher prefers to distance themselves from others.\n\nSome interviewees adapt to technology positively, meaning they find value and benefit in using it. Two interviewees expressed some difficulty in using technological tools, preferring traditional methods. Therefore, their adaptation is slow.\n\nOthers mentioned that they only use certain technological tools when they need them in their classes, which can be considered as pragmatic adaptation. Others utilize technology for specific functions related to their teaching subject, adapting to technology selectively. Finally, there are those who use certain tools because the institution requires them to do so, but it’s not a personal choice; therefore, their adaptation is out of necessity.\n\nThe interviewed teachers are constantly updating themselves. However, their main focus is on monitoring the students, who face difficulties in acquiring knowledge. Furthermore, some interviewed professionals efficiently solve academic problems, adapting to the circumstances, and in certain cases, making use of technology.\n\n\nDiscussion\n\nUpon analysing the responses of the interviewees regarding their experiences and perceptions of techno-stress, new subcategories emerge for analysis.\n\nSeveral studies have delved into the educational context, uncovering disparities in the findings. Some indicate high levels (Alvites, 2019), while others point to moderate levels (Rivadeneira Guerrero et al., 2020; Zheng et al., 2022).\n\nWork overload significantly impacts the physical and psychological well-being of teachers, extending beyond just a heavy workload. Teachers experience physical and mental exhaustion, leading to elevated levels of stress and anxiety (Alvites, 2019; Rivadeneira Guerrero et al., 2020). Work overload manifests in various ways, from planning class sessions to grading assignments and assessments. However, despite these challenges, teachers demonstrate commitment, striving to provide quality education.\n\nUpon analysing the results, it becomes evident that work overload should not be normalized or overlooked. Therefore, it is essential for those responsible for establishing educational policies to implement necessary measures for the well-being of teachers, fostering a healthy environment.\n\nThe research team suggests further exploration of the long-term consequences of techno-stress, not only for teachers but also for students. The aim is to develop strategies that promote the well-being of teachers.\n\nTeachers are capable of effectively managing their emotions through various strategies. The most commonly used strategies include engaging in physical activities and communicating with their students (Romero-Martín & Fraile-Aranda, 2017). Promoting effective communication creates an environment conducive to understanding and empathy. Through these mentioned strategies, teachers maintain emotional balance, enabling them to carry out their pedagogical work despite emotional challenges or difficulties that may arise (Genimon Vadakkemulanjanal et al., 2021). However, recognizing emotions, being inherent to human nature, can be difficult (Francisti et al., 2023). Yet, an educator who manages their emotions and establishes a meaningful connection with their students will cultivate a relationship built on trust and respect.\n\nAppropriate emotional management by teachers can have an impact on the learning process. If students perceive an emotionally healthy environment, they are more likely to be motivated to participate in class activities with a positive attitude toward learning. These findings align with the proposed vital components of teaching (Ch’ng, 2019; Drewelow, 2020; Wetcho & Na-Songkhla, 2022).\n\nWhen addressing the theme of social and emotional interaction from a scientific perspective, the importance of emotional management needs to be grounded. This applies not only to the educational sphere but to any context where individuals interact with others.\n\nFollowing the respective analysis, the team suggests further exploration of this subcategory to identify the effectiveness of different emotional management strategies, such as physical activities and effective communication, in comparison with other techniques like meditation, socioemotional skill training, or psychological counselling. Research could be conducted to examine the impact on the emotional well-being of teachers or to track teachers participating in training programs. This could involve creating both control and experimental groups and subsequently comparing short-term or long-term results. It is imperative to provide robust findings to establish educational policies that promote the emotional well-being of the educational community.\n\nThe interviewees expressed that, despite possessing technological skills, they remain willing to continue updating themselves, even if this leads to pressure or stress for them (Alvites, 2019; Rivadeneira Guerrero et al., 2020). However, it has also been observed that some teachers opt to stick with traditional practices, attempting to distance themselves from technology, or their use of technology is less frequent compared to their colleagues. This diversity of attitudes among teachers towards technology reveals that some leverage the opportunities technology offers and are open to adapting to changes (Bendito Cañizares & Sánchez Botas, 2021; Pribeanu & Gabriel Gorghiu, 2022; Shulga et al., 2021). On the other hand, there are teachers who prefer to remain in a comfortable space and use technology only when necessary or not use it at all (Abarca et al., 2022; De Lima Santana et al., 2022; Morales-Rodríguez, 2021).\n\nFollowing these findings, a deeper exploration of the reasons behind attitudes towards technology in the academic context is necessary. Additionally, identifying factors that influence teachers to either embrace or resist the adoption of new technological trends is essential. By understanding the results of this exploration, strategies can be designed and implemented in the form of updates or workshops within the academic institution.\n\nIt is evident that technology is present in the daily activities of both teachers and students. However, for the optimal use of technology, the active participation of teachers through concrete actions is required (Abarca et al., 2022). Technology alone does not guarantee quality teaching. Therefore, it is essential for teachers to be capable of utilizing technological resources to provide guidance and deliver information to students through various electronic mediums (Delgado-García et al., 2017). The relationship between technology and the willingness of both teachers and students is crucial in enhancing the quality of education.\n\nInvestigating the utilization of technology and its impact on learning, as well as identifying challenges faced in its implementation, is of paramount importance. The findings from such research can be harnessed to design effective strategies and promote the integration of technology within the teaching process. This way, the potential that technology offers can be fully leveraged.\n\nThe research provides insights and tools that can be utilized by teachers, students, or anyone who might be using technology inappropriately. The findings related to techno-stress serve as reference points for enhancing the quality of teaching and promoting efficient technology use within the teaching-learning process. A deeper understanding of the relationship among students, teachers, and technology contributes to emotional well-being for the educational community.\n\nThe research did have several limitations, such as the challenge of objectively measuring techno-stress. The findings are based on teachers’ perceptions, and these perceptions vary among interviewees. Therefore, a qualitative research approach captures the lived experiences of each participant. Another limitation was the influence of personal factors related to technology. For instance, a participant experienced with technology might not recognize that they are actually dealing with technological dependency when interviewed about techno-stress. It is suggested that further research on techno-stress takes an integral and multidisciplinary approach due to the complexity of the phenomenon, whether it serves as a cause or consequence of excessive technology use.",
"appendix": "Data availability\n\nZenodo. Raw data for: Navigating techno-stress: A qualitative exploration of university faculty’s experiences and perspectives in the Peruvian context amidst the return to classes and the post-COVID-19 era. DOI: https://doi.org/10.5281/zenodo.8384995\n\nThis project contains the following data:\n\n- Raw data for: Navigating techno-stress: A qualitative exploration of university faculty’s experiences and perspectives in the Peruvian context amidst the return to classes and the post-COVID-19 era\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nZenodo SRQR checklist. DOI: https://doi.org/10.5281/zenodo.8264791\n\n\nReferences\n\nAbarca R, Buenaño C, Mejía F, et al.: La pandemia COVID-19 inductor de tecnoestrés en docentes de la educación ecuatoriana de segundo nivel. Boletín de Malariología y Salud Ambiental. 2022; 62(2): 266–279. 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Publisher Full Text\n\nMena Freire MA, Ruiz Olarte AM, Vargas Espín A d P: Diferencias de género en la percepción de estrés en universitarios del Ecuador. Ciencia Latina Revista Científica Multidisciplinar. 2022; 6(6): 5916–5928. Publisher Full Text\n\nMorales-Rodríguez FM: Fear, stress, resilience and coping strategies during covid-19 in Spanish university students. Sustainability (Switzerland). 2021; 13(11). Publisher Full Text\n\nNieto Montesinos RM, Paredes Zavala JM, Rivera Flores GW, et al.: Sumajg Warmi: Situación, retos y oportunidades de mujeres científicas en la Costa, Sierra y Selva del Perú. CIES. 2019.\n\nPansini M, Buonomo I, De Vincenzi C, et al.: Positioning Technostress in the JD-R Model Perspective: A Systematic Literature Review. Healthcare (Switzerland). 2023; 11(3). PubMed Abstract | Publisher Full Text | Free Full Text\n\nPribeanu C, Gabriel Gorghiu E-AS: Drivers of continuance intention to use the online learning platform after the Covid-19 pandemic. 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Formación Universitaria. 2021; 14(4): 123–132. Publisher Full Text\n\nShulga TI, Li YJ, Krokhina JA, et al.: Digital technologies’ impacts on student social adaptation during Coronavirus pandemic. World Journal on Educational Technology: Current Issues. 2021; 13(4): 740–748. Publisher Full Text\n\nSimona G, Hana M, Lenka D: Ciberostracismo: Consecuencias emocionales y conductuales en las interacciones en redes sociales. Comunicar. 2021; 67: 9–20.\n\nSuyo-Vega JA, Meneses-La-Riva ME, Fernández-Bedoya VH, et al.: Mental Health Projects for University Students: A Systematic Review of the Scientific Literature Available in Portuguese, English, and Spanish. Frontiers in Sociology. 2022; 7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTondeur J, Hermans R, van Braak J , et al.: Exploring the link between teachers’ educational belief profiles and different types of computer use in the classroom. Computers in Human Behavior. 2008; 24(6): 2541–2553. Publisher Full Text\n\nTorres-Hernández EF: Vocation and burnout in Mexican teachers. Educacion XX1. 2023; 26(1): 327–346. Publisher Full Text\n\nUNESCO - IESALC: Mujeres en la educación superior: ¿la ventaja femenina ha puesto fin a las desigualdades de género? Organizacion de Las Naciones Unidas Para La Educacion, Ciencia y La Cultura. 2021; 1(7): 1–68.\n\nVives Varela T, Hamui Sutton L: La codificación y categorización en la teoría fundamentada, un método para el análisis de los datos cualitativos. Investigación En Educación Médica. 2021; 10: 97–104. Publisher Full Text\n\nWetcho S, Na-Songkhla J: An investigation of pre-service teachers using mobile and wearable devices for emotion recognition and social sharing of emotion to support emotion regulation in mCSCL environments. Contemporary Educational Technology. 2022; 14(2): 1–15. Publisher Full Text\n\nZheng M, Asif M, Tufail MS, et al.: COVID academic pandemic: Techno stress faced by teaching staff for online academic activities. Frontiers in Psychology. 2022; 13(July): 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZotova M, Likhouzova T, Shegai L, et al.: The use of moocs in online engineering education. International Journal of Engineering Pedagogy. 2021; 11(3): 157–173. Publisher Full Text"
}
|
[
{
"id": "218114",
"date": "10 Nov 2023",
"name": "Rajalakshmi S.A.",
"expertise": [
"Reviewer Expertise Social Psychology",
"Positive Psychology",
"Education"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn order to enhance the quality of the article, the authors are encouraged to consider the following recommendations:\n1. Title: The title could be refined for increased catchiness without compromising the essence of the research.\n2. Abstract: It is suggested to augment the abstract by incorporating details about the research approach and design employed, providing a more comprehensive overview.\n3. Introduction:\nSeparate Maslach's Burnout theory and Tondeur’s work into distinct sections, designating Maslach's Burnout theory as the conceptual framework.\n\nIntegrate relevant points from pioneer studies such as Wang et al. (2023) and Khlaif et al. (2023) to enrich the theoretical foundation.\n4. Methods:\nIf the researchers utilized unstructured interview methods, explicitly mention this in the design to preemptively address potential inquiries.\n\nIf alternative interview methods were employed, consider presenting the questions to enhance transparency.\n5. Results:\nGroup emerging concepts and create a thematic map or figure with appropriate headings and captions to visually represent the findings effectively.\n\nInstead of a tabular format, consider presenting interviewee responses in narrative paragraphs, offering profound insights into their perspectives.\n\nIntegrate information on emerging concepts directly into the results section to reinforce the direct link between results and discussion.\n6. Discussion:\nProvide a more in-depth explanation of how grounded theory was employed in the research.\n\nElaborate on the implications of adhering to SAGER guidelines and elucidate on the macro view derived from the results.\n\nit is advisable for the authors to adopt a more expansive perspective, incorporating insights from the results to enrich the discourse.\n7. Conclusion:\nCraft a concise yet comprehensive conclusion that encapsulates the key findings and their broader implications.\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": "231297",
"date": "21 Dec 2023",
"name": "Zuheir N Khlaif",
"expertise": [
"Reviewer Expertise Technology 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\nDear Authors, Thank you for submitting your manuscript for consideration by our journal. The topic is intriguing, and I appreciate the effort. However, there are several areas that need improvement before it can be considered for publication. Abstract: Please include the purpose of your research, the context, the number of participants, and details about the methodology and data analysis process. While some of these elements are present, they are not sufficiently detailed. Introduction: This section should clearly define your research problem. I was searching for the problem/motivation behind your research but did not find it. Additionally, the purpose of your study and its contribution to the field should be articulated. Literature review Improve your LR by adding new articles and related ones. I suggest the following articles to include in your research in different stages, especially the methodology and discussion https://link.springer.com/article/10.1007/s40299-021-00638-x https://www.cell.com/heliyon/pdf/S2405-8440(23)06277-1.pdf https://www.mdpi.com/2227-9032/11/3/446 https://link.springer.com/article/10.1007/s10758-022-09607-9 https://link.springer.com/article/10.1007/s10639-023-11651-6\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "234914",
"date": "09 Mar 2024",
"name": "Maria Amelia Eliseo",
"expertise": [
"Reviewer Expertise She is a researcher at the research group TecInt - Interactive Technologies and MackLEAPS - Laboratory for Studies of Software Production Environments. Coordinates the research projects \"ICT evaluation to boost the technological transformation of micro and small enterprises in the incorporation of Industry 4.0 with a focus on human factors\" and \"Usability and Accessibility Analysis in Inclusive Games for Seniors\". He has experience in Human-Computer Interaction",
"Web Technologies (Accessibility and Usability)",
"Virtual and Augmented Reality",
"Interaction Design."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Authors, The article presents a qualitative research carried out with 10 Higher Education teachers involving four aspects: Work Overload; Social and Emotional Interaction; Adaptation to new Technologies and Expectations and quality of Teaching. It is a current and relevant subject in the area of Education. Here are some comments to improve the text.\nAlthough the title refers to the post COVID-19 era, it is not clear in the text this relationship. Perhaps it could only contextualize the COVID-19 era, with the obligation for higher education teachers to adhere to the use of technology for their online classes and treat techno-stress as a current reality in the academic community. Although the Introduction presents the theoretical foundation and the research question, it failed to show the contextualization of the problem and detail the research objectives. In Methods, you could detail in which period the interviews were conducted. How were they planned and conducted? How were the SAGER guidelines applied? In Results, Figures 2, 3, 4, and 5 were not contextualized. What would the authors like to show to readers with these figures? At the end of the article I missed the conclusion and the notes of some future work. I suggest the following reference to support the discussions:[1]\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? 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/12-1381
|
https://f1000research.com/articles/13-958/v1
|
23 Aug 24
|
{
"type": "Research Article",
"title": "The macroeconomic determinants of trade openness in Latin American countries: A panel data analysis",
"authors": [
"Rogger Orlando Morán Santamaría",
"Yefferson Llonto Caicedo",
"Francisco Eduardo Cúneo Fernández",
"Lizana Guevara Nikolays Pedro",
"Castro Mejía Percy Junior",
"Milagros Judith Pérez Pérez",
"Lindon Vela Meléndez",
"Moises Elias Montenegro López",
"Yefferson Llonto Caicedo",
"Francisco Eduardo Cúneo Fernández",
"Lizana Guevara Nikolays Pedro",
"Castro Mejía Percy Junior",
"Milagros Judith Pérez Pérez",
"Lindon Vela Meléndez",
"Moises Elias Montenegro López"
],
"abstract": "Background Trade openness shows a positive impact on economic growth, supported by economic theory, and export diversification and economic complexity show a positive dynamic in trade openness in the world; however, a specificity is generated in South American countries. Therefore, the objective of the research is to analyse the macroeconomic determinants of trade openness in Latin American countries.\n\nMethods The research approach was quantitative and explanatory using panel data methodology from the databases of the World Bank, Harvard University and the Economic Commission for Latin America and the Caribbean for the period 2000-2020.\n\nResults The fixed effects panel data model showed that the variables that had a negative impact on trade openness were GDP, the economic complexity index and the logistic performance index, while the variables that had a positive impact were exports of high-tech products (a proxy for innovation), exports, imports, research and development expenditure and interregional trade in goods.\n\nConclusions Therefore, during the analysis period of 2000-2020 in South America, based on the panel data analysis under fixed effects, a total of 8 countries had a negative impact on trade openness, and only the economies of Chile, French Guiana, and Brazil had a positive impact on trade openness; these economies are characterized by their better performance in the economic complexity index, their higher percentage of budget for research and development expenses, and their trade policies oriented towards the industrialization of their value-added products.",
"keywords": [
"Trade openness",
"impact",
"panel data"
],
"content": "1. Introduction\n\nTrade openness in countries around the world has shown significant relevance in addressing one of the greatest global crises, where the acute and real problem of global food security, coupled with rising inflation, demonstrates that trade policies not only ensure adequate access to food but also compel a consideration of the link with economic complexity, which in turn requires research and development and the creation of an innovation climate that impacts economic growth (Bardi & Hfaiedh, 2021; Fusco et al., 2020; Gallego & Zofío, 2018; Tabash et al., 2022). Moreover, sustainable trade practices are crucial for promoting long-term economic resilience, environmental protection, and social well-being, aligning with the broader goals of sustainable development.\n\nThe debate focuses on the so-called resource curse, where Latin American economies show that after the decades of the eighties and nineties, they developed a strategy for diversifying exports and boosting the reorientation of the external sector where goods of medium and high technological intensity are produced; while other countries such as Peru, Ecuador, Bolivia, Chile, Colombia, Paraguay, and Venezuela based their trade basket on the primary sector as the support of the export industry (Alvarado & Guzmán, 2019; Gnangnon, 2022; Tabash et al., 2022).\n\nThe growing international trade flow, the development of technological capabilities, research and development, and economic complexity have had a direct and significant impact on sustainable economic growth. From the theoretical perspective of economic policy for sustainable growth, trade policy plays a fundamental role in the state, as market economies require the existence of an efficient and effective state that can ensure compliance with free trade rules (Cetin et al., 2018; Chávez, 2021; Lima & Alvarez, 2018).\n\nIn the region of South America, according to data from the Economic Commission for Latin America (2021) in Argentina, the average growth of trade openness, which allows assessing the magnitude of foreign trade relative to a country’s internal production, was 28% in the period 1990-2022, being volatile and reaching the highest percentages of openness degree in the period 2002-2008 then showing a decline and reaching 31.7% in 2022.\n\nIn the case of Bolivia, the average trade openness indicator reached 60.1% in the period 1990-2022, and from 1990 to 2008 showed an increasing trend, reaching 67.8% in 2022. For Brazil, the average growth of trade openness was 24.3% in the period 1990-2022, with an increasing trend until reaching 38.8% in 2022.\n\nMeanwhile, in Chile, during the period 1990-2022, an average of 62.4% was reached, achieving 75% in 2022; in the case of Colombia, the average reached during the mentioned period is 35.3% and in 2022 reached 48.4%. In the case of Ecuador, the average trade openness indicator reaches 50.9% and in 2022 reached 57.7%; for Paraguay, it reached a degree of openness of 82.8% in the period 1990-2022; while Peru reached 42.4% in the same period; and Uruguay reached 52.7%.\n\nThe arguments in favor of trade liberalization start from the greater accumulation of physical capital but face diminishing returns; while the growth lever bets on the accumulation of knowledge, which generates significant and dynamic impacts that lead companies needing access to large markets to innovate and become more competitive given the fluidity towards the ability to learn and assimilate new technologies (Corrales Sillo, 2021; Mesquita & Stein, 2019).\n\nWhile trade openness has empirically shown positive externalities for economies, such empirical evidence still lacks clear empirical factors, especially in Latin American economies where the impact is estimated to be an acceleration of between 0.6 and 0.7 percentage points on average to the annual growth of per capita gross domestic product. This is mainly due to the role of political, institutional, and structural factors related to technology and innovation; given the particularities of the countries that make up the South American region, the low levels of human capital and the distant technological frontier may have affected trade openness, diminishing the positive impact of trade liberalization as addressed by economic theory (Grossman & Helpman, 2015; Goldberg & Pavcnik, 2016).\n\nHowever, there is no doubt that trade openness has led to leaving behind apocalyptic decades in Latin America; it was the shift in trade policy that originated a positive contribution to development and well-being (Herreros and Rosales, 2013; Lopez & Munoz, 2020); as Boloña (1993) held, “precisely because we are a small country in economic terms, we must diversify our markets, expand the scale of our economy, benefit from international markets to grow and accumulate capital, to overcome poverty and achieve the desired levels of well-being and prosperity“(p.13).\n\nFalcón (2021) begins from the challenge of directing trade policy towards a greater degree of diversification of productive matrices that allows countries to achieve greater economic complexity based on a greater accumulation of knowledge and not just on the aspect of more physical capital or working capital, leading to bet on technological development and the transformation of the basket of exportable products leading to manufactured goods with added value, surpassing the threshold of commodities and developing comparative advantages, with a relationship between trade openness, economic complexity, innovation, research and development, and economic growth (Lee & Lee, 2020; Shahzad et al., 2022); understanding the particularity of each country in its productive transformation based on the existing connection between the variables under study, which will lead to a public policy decision to achieve the transformation of the external sector for sustainable growth with development prospects in emerging economies (Yang et al., 2023; Cheong, 2023).\n\nIn this context, the present article aims to analyze the macroeconomic determinants of trade openness in Latin American countries; thus, posing the question: What are the macroeconomic determinants of trade openness in Latin American countries: a panel data analysis? considering the explanatory variables of economic complexity, innovation, research and development, and economic growth for the mentioned period.\n\nThe contribution, considering the specificity of the model that proves to be crucial for policymakers, takes into account that the study is only conducted in South American countries over a specific period from 2000 to 2020 and contributes to the empirical evidence of considering the importance of better integrating into the global economy by achieving greater competitiveness and considering trade openness from an important position in income distribution and poverty reduction that benefits generating investment and dynamism in international trade in the region.\n\n\n2. Literature review\n\nRecent empirical evidence has been highlighting the importance of the external sector through trade openness as an economic policy in the growth of emerging economies like those in Latin America, in a current scenario of health crisis and food security, as well as economic uncertainty that has underscored the importance of diversification and complexity of exports, leading to a restructuring of the productive matrix which in turn requires the accumulation of physical capital and the expansion of capabilities. This necessitates developing a climate of business innovation as well as allocating more resources to research and development (Carrasco, 2021; Chávez, 2021; Bashir et al., 2020; Chacha et al., 2024; Guo et al., 2023; Mania & Rieber, 2019; Nieminen, 2020).\n\nIn the international environment, Wang et al. (2023) conducted a study evaluating economic complexity, trade diversification, renewable energy consumption, and environment-related taxes to generate growth during the period 1995-2018. It was identified that the aforementioned variables significantly propelled the growth of BRICTS countries, generating important policy implications for achieving marginal contributions.\n\nFor Li and Rigby (2023) economic growth has a positive and significant relationship with complex technological diversification. Evidence of spatial autocorrelation and endogeneity confirms the positive link between technological advancement and economic growth in China between the periods 1991-1995 and 2011-2015, where measuring knowledge complexity has generated a positive relationship, the result of the regression showing that intelligent specialization has led to a knowledge development trajectory for achieving regional competitive advantage.\n\nThe nexus between innovation, trade openness, financial development, and economic growth using the panel VAR approach in 11 European countries over the period 2001-2016 reveals a unidirectional relationship between economic growth and financial development; as well as trade with economic growth and the negative relationship between innovation and economic growth and between trade and economic growth. Thus, the important role of each country depends on the role that innovation and productivity play, recommending that the quality of institutions is fundamental to improving the regulatory environment to achieve optimal trade openness and generating incentives for innovation in local companies to address the negative effects generated by trade openness (Mtar & Belazreg, 2023).\n\nVarious studies show the relationship between the explanatory variables of economic complexity, innovation, research and development, and economic growth.\n\nIn 28 African countries, considering a panel data analysis, the mediating effect of economic complexity and the natural resource-based growth model for the period 1995-2019 has been considered. The empirical evidence indicates that the positive effect of natural resources on economic growth in the short and long term, generating robust results, where economic complexity seeks to formulate policies to achieve links between the variables of natural resources and economic growth using economic complexity (Mesagan & Vo, 2023).\n\nIn Russia, high-tech companies that generate new products and markets are a key factor in long-term economic development, where the region’s export basket reflects operations in the directions of technological development to diversify a technological chain with higher added value and hence competitiveness of export-oriented products, creating knowledge-intensive and high-technology sectors aimed at developing local advantages and market expansion with interregional cooperation (Goryushkin & Khalimova, 2023).\n\nThus, the diversification of exports and economic complexity is receiving relevance in the scientific literature so that the results of structural equation models generate a positive relationship between economic complexity and per capita economic growth of each country. The results show that both the level of per capita gross domestic product and economic vulnerability infer on economic complexity, given the economic challenges faced by countries with low growth, high unemployment, rising debt, and regional vulnerability (Ben Saad et al., 2023).\n\nFor Rahman et al. (2023) in Bangladesh, economic growth is argued in terms of technological innovation, foreign direct investment, trade, and human capital over the period 1990-2020, using time series for the dynamic simulation ARDL method, where cointegration and the symmetrical long- and short-term associations between the variables, consider that technological innovation and human capital have a long-term relationship with economic development in the country. Generating the contribution of a significant correlation between economic growth and the described variables in the short term, considering the robustness of the study.\n\nFor Bardi and Hfaiedh (2021) evidence shows a positive impact of trade openness on economic growth, revealing unidirectional causality based on economic theory where trade openness has positive effects on economic growth (Barro & Sala, 2009; Lucas, 1988; Romer, 1986; Banday et al., 2021; Zaman et al., 2021).\n\nCanh and Thanh (2022) for their part, evidence that the diversification of exports and economic complexity show a positive dynamic, presenting bidirectional causality given the role played by the quality of export products which is measured from the productive capacities of a country to add value to its export products achieving more competitiveness through the structural transformation of economies and the diversification of the productive matrix of countries (Armas et al., 2020; Shahzad et al., 2022; Lapatinas et al., 2019; Koch, 2021).\n\nFor Mesquita and Stein (2019) they consider that although the great trade liberalization in Latin America has led to a positive impact on economic growth and well-being being the channel that helped recover much of the economies of Latin America from their participation in trade in the gross domestic product in the region that reached 28% they still face challenges in terms of technological aspect and innovation to continue the solid growth of international trade; this because there are comparative advantages that allow productivity leaps (Llanos & Brown, 2021; Vela et al., 2021).\n\nFor Chávez (2021) considers in the panel data model two related equations innovation as the dependent variable and trade openness as the independent variable and as a second equation was obtained as the dependent variable to the predictions of innovation and trade openness as the explanatory variable.\n\nMeanwhile, Fusco et al. (2020) considers in their analysis of dynamic panel data where they analyze food security and trade openness developing three regression equations with indicators of trade openness, tariffs, and globalization. While Cetin et al. (2018) considers economic growth, energy consumption, trade openness, and financial development as explanatory variables and carbon emissions as the dependent variable for the case of Turkey.\n\n\n3. Theoretical basis\n\nGräbner et al. (2021) believe that international trade generates economic growth, suggesting that while trade openness is not a direct or robust determinant in economic growth, it contributes significantly to it. By leveraging growth potential, greater trade openness generates ideas and knowledge, along with their respective technical advancements, to open up new goods and services in international trade, contributing from the theory of the openness paradigm and initiating a debate on the causality of growth (Silajdzic et al., 2018).\n\nHartmann (2014) from the contribution of economic theory, considers that growth is linked to the increase in production, income, and consumption. Meanwhile, the classic view of Smith (1976) considers that both the division of labor and trade are key aspects to achieving growth, explained by the classical factors of capital, labor, and land, but with an additional factor related to technology (Solow, 1956). Subsequently, approaches to economic growth explained by technological progress emerged, providing a different perspective on long-term growth (Romer, 1986) with technology as an exogenous factor of growth rather than an endogenous one.\n\nHausmann et al. (2020) consider the theory of economic complexity, which involves moving away from traditional factors to focus on knowledge as the main value generator for achieving a new structural transformation that allows diversifying the productive matrix and empowering the aspect of greater competitiveness. For Hidalgo and Hausmann (2009) economic complexity refers to the set of a region’s export products that shows a country’s productive capacity based on existing capabilities and know-how, implying that the more diverse and value-added the export products, the more productive the region is considered.\n\nThe paradigm of innovation and structural changes have become prominent in recent literature due to the composition of new economic systems where creation, innovation, and entrepreneurship have led to major changes in countries like India, China, and the United States, whose knowledge-based growth has led to their exponential development. Schumpeter (1941) in his theory of economic development addressed that innovation, as well as inventions by scientists, would lead to creating entirely new investment, growth, and employment opportunities. According to Schumpeter and Swedberg (2003) the innovation process can be divided into four dimensions: invention, innovation, diffusion, and imitation.\n\nElfaki and Ahmed (2024) consider that as a result of technological adoption, these elements are fundamental for the economic growth of any nation. In a world where global competition is increasingly intense, the ability to innovate and continuously improve becomes a determining factor for economic success. R&D drives progress, not only through the creation of new products and services but also by optimizing existing processes, thus increasing productivity and efficiency across various industries.\n\nCompanies that allocate resources to research and development tend to be at the forefront of creating novel products and services that better meet consumer needs. This not only makes them more competitive but also enables the creation of new industries and markets, which in turn can lead to sustained economic growth.\n\nBeing the hypothesis that economic complexity, innovation, research and development, and economic growth are the determinants of trade openness.\n\n\n4. Methods\n\n4.1.1 Type of research\n\nA quantitative approach is considered, with a type of explanatory research that corresponds to identifying the impact of economic complexity, innovation, research and development, and economic growth on the trade openness of South American countries during the period 2000-2020.\n\n4.1.2 Research design\n\nThe variables analyzed have not been modified, and the research is a non-experimental design; therefore, it has been verified that it was conducted in a specific context of the South American countries and the interaction of the unmanipulated variables (Hernández et al., 2018).\n\n4.1.3 Population\n\nThe population involves a total of 2079 data points across 9 analyzed variables considering a total of 11 South American countries, noting that we have 231 data points per variable for each country under analysis during the 2000-2020 period.\n\n4.1.4 Sample\n\nThe sample is equal to the population and comprises a total of 2079 data points across 9 analyzed variables considering a total of 11 South American countries, noting that we have 231 data points per variable for each country under analysis during the 2000-2020 period.\n\n4.1.5 Unit of analysis\n\nThe unit of analysis consists of each South American country, involving a total of 11 countries analyzed during the 2000-2020 period.\n\n4.1.6 Data collection techniques and instruments\n\nFor measuring the variables, documentary analysis was used as the technique, and the observation guide served as the instrument, which is a tool used to collect data systematically and structured during an observation or study.\n\n4.1.7 Data collection procedures\n\nThe data obtained from the World Bank corresponded to the explanatory variables of gross domestic product, imports, exports, high-tech product exports, research and development expenditure, and the logistics performance index; as well as from the Harvard University Economic Complexity Atlas, where information on the economic complexity index was obtained. Regarding the interregional trade of goods variable, it was obtained from the database of the Economic Commission for Latin America and the Caribbean during the mentioned analysis period.\n\nA panel data model is used, where from this model, the impact of economic complexity, innovation, research and development, and economic growth on the trade openness of the South American countries during the 2000-2020 period is quantified. To perform the estimates consistently and achieve a proper analysis, the variables have been transformed into logarithms such as gross domestic product, imports, exports, high-tech product exports, and total interregional trade of goods.\n\nThe databases used for this research stem from international institutions such as the World Bank, Harvard University, and the Economic Commission for Latin America for the period 2000-2020.\n\nIn the estimation, we have used the panel data model based on economic literature that demonstrates a positive impact of trade openness on economic growth (Romer, 1986; Barro & Sala, 2009; Lucas, 1988; Katz, 1999).\n\nHighlighting the importance of export diversification and complexity, leading to restructuring the production matrix, which in turn requires the accumulation of phys-ical capital and expansion of capacities, thereby necessitating the development of a climate of entrepreneurial innovation, as well as allocating greater resources to research and development (Carrasco, 2021; Chávez, 2021).\n\nEquation 1 establishes the relationship of the dependent variable trade openness with exports, imports, and gross domestic product per country in South America i =1, 2, …………. 11 in the year t = 2000-2020.\n\nOn the other hand, the incorporation of the variable’s economic complexity (eco-nomic complexity index), innovation (proxy: exports of high-tech products), research and development (percentage expenditure on research and development), the logistic performance index, and total interregional trade of goods are evidenced in the following equation:\n\nNext, the Generalized Least Squares (GLS) model is estimated because the equations present problems of heteroskedasticity and autocorrelation detected with the Breusch and Pagan (1979) (as cited in Onali et al., 2017) and Wooldridge (2010) Lagrange Multiplier tests. Furthermore, to choose between a fixed or random effects model, the Hausman test (1978) (as cited in Onali et al., 2017) is utilized.\n\nThe variables used in the proposed panel data model are detailed in the following Table 1.\n\nThe data were analyzed using an econometric panel data model that captures the bidimensionality of the data. This model allows for the quantification of the impact of economic complexity, innovation, research and development, and economic growth on the trade openness of South American countries during the period 2000-2020. The data were obtained from the World Bank, Harvard University, and the Economic Commission for Latin America and the Caribbean and processed in Eviews 12 and is used for the estimation of the panel data model, considering the control variables that are subjected to the proposed equations to analyze the interrelationship between the variables (Figure 1). This allows for both descriptive statistical treatment and the estimation of the proposed panel data model and the Generalized Least Squares (GLS) model. An academic license for the use of Eviews 12 software is available, registered under the name Lindon Vela Meléndez. The license details are as follows: Serial number: Q1208886 - D49010AF - 9D854485. The software can be downloaded from the following link: http://www.eviews.com/download/student12.\n\nNote: Own elaboration with data from World Bank (2024), Harvard University (2024), Economic Commission for Latin America (2024), for the period 2000-2020, using Eviews 12.\n\nFurthermore, the Generalized Least Squares (GLS) model was employed due to issues of heteroscedasticity and autocorrelation identified in the structural equations. These issues were detected using the Breusch and Pagan (1979) (as cited in Onali et al., 2017) Lagrange Multiplier test and the Wooldridge (2010) test. Additionally, the Hausman (1978) (as cited in Onali et al., 2017) test was used to decide between a fixed or random effects model, which helps in choosing the most suitable model based on the consistency of the estimators.\n\nThe data for this study were obtained from international institutions such as the World Bank, Harvard University and the Economic Commission for Latin America for the period 2000-2020. Access to the data is public and free of charge on the detailed websites and adheres to rigorous ethical standards to protect the confidentiality of the published data.\n\nIn addition, the data from the World Bank, Harvard University and the Economic Commission for Latin America is an effort by international institutions to generate databases that allow interaction with public policy makers.\n\nAlthough we cannot provide specific details on the process of obtaining the data, it is imperative to indicate that, as prestigious governmental institutions such as the World Bank, Harvard University and the Economic Commission for Latin America, there is a use and policies to access under ethical practices in the generation of data in the respective public repositories and free access and obtaining informed consent.\n\nFor the ethical use of public data obtained by the World Bank, Harvard University and the Economic Commission for Latin America, we adhere to the principles of intellectual honesty, truthfulness, transparency, human integrity, respect for intellectual property, justice and responsibility, the study aims to comply with the “Code of Ethics in Research of the Universidad César Vallejo, version 01; by Resolution of the University Council N° 0340-2021-UCV”, code of ethics that was used throughout the development of the scientific article, since as main author we work all scientific activity respecting the code of ethics of the UCV university.\n\nWe have used the data from the described repositories for research purposes only, as permitted by the conditions of use by the World Bank, Harvard University and the Economic Commission for Latin America. We have not attempted to modify any data, and our analysis does not include any personally identifiable information.\n\nBy using publicly available anonymized data and adhering to ethical principles in our research, we aim to minimize any potential ethical issues while leveraging valuable information for the benefit of research in economic science.\n\n\n5. Results\n\nThe research utilizes data sourced from the World Bank, Harvard University, and the Economic Commission for Latin America and the Caribbean. Descriptive statistics for each variable analyzed are presented in Table 2, including the mean, standard deviation, minimum, maximum, skewness, and kurtosis. Additionally, the correlation matrix between the variables under analysis is provided. It shows that exports, imports, gross domestic product (GDP), the economic complexity index, total interregional trade of goods, and research and development had a negative relationship with trade openness, whereas the export of high-technology products and the logistics performance index had a positive correlation with trade openness during the period 2000-2020. The negative relationship indicates that South American countries, except for Chile and Brazil, have shown less trade openness in their economies over the last decade with respect to the international market. According to the Economic Commission for Latin America and the Caribbean (2021) economies in South America have demonstrated reduced trade openness due to the slowdown in international trade despite their high dependence on imports and extensive trade relations with major global economic powers in a scenario of economic uncertainty and a political shift to the left, which helps to understand which variables are influencing reduced trade openness (Figure 2).\n\nNote: Own elaboration with data from World Bank (2024), Harvard University (2024), Economic Commission for Latin America (2024), for the period 2000-2020, using Eviews 12.\n\nThe standard deviation indicates that there is greater variability among the variables of export of high-technology products, exports, imports, gross domestic product, and total interregional trade of goods, with a total of N data points equivalent to 231 observed data per variable representing the total number of 2079 observations across the 9 variables studied during the period 2000-2020 for the 11 South American countries. This variability and the detailed analysis of the correlations provide insights into the complexities of trade dynamics and economic interactions in the region, underscoring the nuanced impact of various economic factors on trade openness.\n\nThe estimated regression results, considering the Wooldridge (2010) test, indicate the presence of autocorrelation across the panels. Additionally, the Breusch and Pagan (1979) (as cited in Onali et al., 2017) Lagrange Multiplier test shows that the estimations had issues with heteroscedasticity; these issues have been corrected using Generalized Least Squares (GLS) to address both heteroscedasticity and autocorrelation.\n\nTable 3 displays the results of the panel data estimation, revealing that public health spending, rural population, unemployment, and gross domestic product are statistically significant at the 5% level considering equation 2.\n\n** p<0.05.\n\n* p<0.1.\n\nTo determine the best model (fixed or random effects), the Hausman Test is used, which compares the beta coefficients obtained through the fixed and random effects estimators, identifying whether the differences between them are significant. In both cases, the weight matrix is homoscedastic. Thus, considering that the Prob > Chi2 is less than 5%, the fixed effects model is employed, which shows a higher global significance of 94.5%.\n\nThe interpretation of the fixed effects details that for every 1% increase in the exports of high-technology products, trade openness increased by 0.05%. Similarly, a 1% increase in exports raises trade openness by 0.30%; a 1% increase in imports leads to a 0.09% increase in trade openness; a 1% increase in total interregional trade of goods increases trade openness by 0.005%; and a 1% increase in spending on research and development results in a 0.14% increase in trade openness. Regarding gross domestic product, a 1% increase led to a 0.42% decrease in trade openness. For the economic complexity index, a 1% increase resulted in a 0.08% decrease in trade openness, and for the logistics performance index, a 1% increase led to a 0.13% decrease in trade openness during the analysis period 2000-2020.\n\nThese findings provide valuable insights into the factors that influence trade openness in South American countries, highlighting the complex interplay between various economic and logistical variables. The results underscore the importance of considering both economic structures and policy environments when assessing the openness of trade regimes.\n\n\n6. Discussion\n\nThe impact of economic complexity, innovation, research and development, and economic growth on the trade openness of South American countries in the period 2000-2020 shows a differential behavior. These countries have exhibited lower trade openness in their economies over the last decade compared to the international market. Additionally, there is a reduced economic complexity due to lower diversification of productive matrices in export baskets, resulting in economies still heavily reliant on commodities or primary export products.\n\nThe greatest decline in trade openness is observed in Venezuela, with a negative impact of 104%. This is attributed to the country’s current economic crisis characterized by inflation and high prices of its oil commodity, coupled with a closed economy model. Among the remaining market economy countries, negative impacts are noted in Peru (15%), Ecuador (16%), Argentina (16%), Uruguay (10%), Bolivia had the greatest decline in Trade Openness at 18%, Ecuador and Argentina had 16%, Colombia had 13%, and Paraguay had 10%; these declines were due to diminishing returns and the accumulation of physical capital. Conversely, Chile, French Guiana, and Brazil have experienced positive impacts of 12%, 31%, and 25%, respectively. These economies are characterized by better performance in the economic complexity index, higher percentage of budget allocated to research and development expenses, and trade policies focused on industrializing value-added products such as high-tech products (Figure 3).\n\nNote: Own elaboration with data from World Bank (2024), Harvard University (2024), Economic Commission for Latin America (2024), for the period 2000-2020, using Eviews 12.\n\nThese results align with the findings of the Economic Commission for Latin America and the Caribbean (ECLAC, 2021), which has shown that economies in South America have exhibited lower trade openness due to the slowdown in international trade. Countries such as Peru, Ecuador, Bolivia, Chile, Colombia, Paraguay, and Venezuela have relied on their primary sector as the backbone of their export industry.\n\nFurthermore, these results are consistent with the findings of Mesquita Moreira and Stein (2019), who found that while significant trade liberalization in Latin America has led to a positive impact on economic growth, challenges remain in terms of technological aspects and innovation to sustain solid international trade growth. There are still comparative advantages that allow for productivity leaps, yet South American countries have not yet taken off in terms of innovation and thus achieving higher productivity.\n\nCorrales Sillo (2021) and Mesquita Moreira and Stein (2019) also suggest that the aforementioned results indicate that South American economies still lack knowledge accumulation, which translates into a lack of innovation. To address this, policies focusing on innovation and development are needed to add more value to export products and access larger markets, thereby enhancing competitiveness. These economies are characterized by diminishing returns due to the accumulation of physical capital.\n\n\n7. Conclusions\n\nIn the analysis period of 2000-2020, South American countries exhibited differential behavior as they showed lower trade openness in their economies compared to the international market. Additionally, there was lower economic complexity due to less diversification in export baskets, resulting in economies still based on commodities or primary export products.\n\nBased on panel data analysis using fixed effects, a total of 8 countries—Peru, Ecuador, Argentina, Uruguay, Bolivia, Colombia, Paraguay, and Venezuela—experienced a negative impact on trade openness. Only the economies of Chile, French Guiana, and Brazil showed a positive impact on trade openness, characterized by better performance in economic complexity indices. These countries allocate a higher percentage of their budget to research and development and pursue trade policies aimed at industrializing products with added value.\n\nInterpretation of fixed effects reveals that the variables with the greatest impact on trade openness during 2000-2020 were gross domestic product, logistics performance index, economic complexity index, exports, imports, and research and development expenditure.\n\nWhile significant trade liberalization in Latin America has led to a positive impact on economic growth, challenges remain in terms of technological aspects and innovation to sustain solid international trade growth. South American countries still struggle to innovate and achieve higher productivity, facing a slowdown in international trade despite high dependence on imports and extensive trade relations with major global economic powers amidst economic uncertainty and a shift towards left-wing political systems.\n\nFor South American countries, it is recommended to strengthen policies that promote investment in research and development to drive innovation, as well as enhance education in science, technology, engineering, and mathematics to foster creative industries that add value to primary export products.\n\nDeveloping strategic investment planning for infrastructure such as roads, ports, airports, and information technologies is essential to improve connectivity and facilitate the transportation of goods and services, thereby boosting energy efficiency and reducing logistical production costs.\n\nIdentifying the positive effect of trade liberalization on economic growth in Latin American countries, albeit unsustainable, calls for the development of clusters as a key strategy to foster competitiveness and specialization in specific sectors of the economy. This could be accompanied by fiscal and financial incentive programs to encourage investment in research and development, as well as the establishment of industrial parks, shared laboratories, and innovation centers to optimize connectivity and logistics.",
"appendix": "Data availability statement\n\nZenodo. The macroeconomic determinants of trade openness in Latin American countries: A panel data analysis. https://doi.org/10.5281/zenodo.13207898 (Morán et al., 2024).\n\nThis project contains the following underlying data:\n\n• Final results of the database.xlsx\n\nThis project contains the following extended data:\n\n• Rectoral Resolution N° 760-2007_UCV_Code Of Ethics.pdf\n\n• STROBE_checklist_v4_combined.pdf\n\n• Figure 1_Correlation of model variables\n\n• Figure 2_Trade openness index by country\n\n• Figure 3_Impact on trade openness by country\n\nCreative Commons Zero v1.0 Universal (CC0 License)\n\n\nReferences\n\nAlvarado Guzmán AR, Guzmán A: Análisis exploratorio de la apertura comercial del Ecuador frente a Perú y Colombia. Rev. Econ. Polit. 2019; XV(29): 9–24. Publisher Full Text\n\nArmas Arévalos E, Javier Ayvar Campos F, Favila Tello A: La apertura comercial y el desarrollo de capacidades tecnológicas en México.2020. 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}
|
[
{
"id": "323039",
"date": "26 Sep 2024",
"name": "Olimpia Neagu",
"expertise": [
"Reviewer Expertise Economic complexity",
"Economic modelling"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral comments: The paper is appropriately conceived and structured. Introduction section is well developed. Literature review cites the current literature on the macroeconomic determinants of trade openness. Variables selection is justified and the methodology design is explained Conclusions are supported by the paper’s results.\nRecommendations: I suggest to rename the Section 4. Methods in: 4. Methodology and data Title 4.2 is in Spanish, please correct it.\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": "323042",
"date": "18 Oct 2024",
"name": "Kingsley Appiah",
"expertise": [
"Reviewer Expertise Environmental management",
"Sustainability management",
"Panel data modelling"
],
"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 1.The statement at the introduction section such as ‘Trade openness in countries around the world has shown significant relevance in addressing one of the greatest global crises, where the acute and real problem of global food security, coupled with rising inflation, demonstrates that trade policies not only ensure adequate access to food but also compel a consideration of the link with economic complexity, which in turn requires research and development and the creation of an innovation climate that impacts economic growth (Bardi & Hfaiedh, 2021; Fusco et al., 2020; Gallego & Zofío, 2018; Tabash et al., 2022)’. The statement is too long which ends up distorting what the researchers are trying to communicate. I suggest that the authors make it brief.\n2. I suggest that authors improve on the flow of the write-up and how the various paragraphs under the introduction section are connected to make much more sense. There is a lack of coherence in the introductory section which makes it difficult to understand what the authors are trying to send around. 3. In terms of the study gap identified, authors should bring into perspective what has already been done in the study areas and what this particular study seeks to address as a gap.\nLiterature review 4. The same can be said about the literature section of the study. The authors failed to connect the various scholars' work to make the section more coherent and interesting. Although authors made use of current research work by scholars the literature strand depicts a write-up of other researchers' work put into paragraphs. I suggest that the authors improve on the literature section of the study. 5. I suggest that authors classify the literature section into empirical and theoretical study 6. I suggest authors move the discussion of the variables under study from the theoretical basis section to theoretical study under a subheading named conceptual terms. At the same time, 3.1 and 3.2 are under the subheading ‘study theories’.\nMethods 7. I suggest authors merge the following subheadings and put them under these subheadings title: Merge 4.1.1 & 4.1.2 as 4.1 Research design Merge 4.1.3, 4.1.4 & 4.1.5 as 4.2 Population and sampling Merge 4.1.6 & 4.1.7 as 4.3 Data collection technique & procedure\nResults 8. Since the authors’ analysis is based on a panel dataset, I expected them to perform certain fundamental or preliminary tests, such as the cross-sectional dependency test, unit root test, and cointegration test. I suggest that the authors perform these basic tests and discuss them in the results section while describing them in the methods section. 9. Proofreading the work would help.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "13272",
"date": "07 Feb 2025",
"name": "Rogger Orlando Morán Santamaría",
"role": "Author Response",
"response": "Kingsley Appiah Kumasi Technical University, Kumasi, Ashanti Region, Ghana Please accept our best regards from the authors of the article. We appreciate your comments and know that they improve the quality of our finalised research. I am writing to inform you that the report has been uploaded with the suggested changes and that we can continue with the process of publishing the article to the highest standards of quality. We hope we have met your requirements. We look forward to hearing from you. Thank you very much."
}
]
}
] | 1
|
https://f1000research.com/articles/13-958
|
https://f1000research.com/articles/13-835/v1
|
25 Jul 24
|
{
"type": "Research Article",
"title": "Relevance of Competency Based Education for Architectural Education in India",
"authors": [
"Nikhil Kohale",
"Pradeep Kini",
"Ciraj Mohammed",
"Nikhil Kohale",
"Ciraj Mohammed"
],
"abstract": "Background A holistic architectural education is the culmination of learning knowledge, skills, attitudes, and values, which eventually reflects in the quality of graduates. Even though different schools of thought have made various kinds of qualitative contributions towards the evolution of architectural education in India, it has largely been dominated by the quantitative and technical aspects of its regulating framework. Architects engage with the demanding contradictions between responsibilities of an ethical nature, the dynamic challenges of practice, and the intricacies of architectural imagination. The aesthetical and imaginative foundations of the field make it incumbent upon the architects to possess a balance of ecumenical proficiencies for accountability and personalization. The purpose of the study is to identify relevant attributes of Competency Based Education (CBE) that can be adopted for architectural education in India.\n\nMethods This research follows a narrative review approach and a descriptive-analytic method to broadly understand the attributes of CBE and its potential relevance to architectural education in India. 313 articles were searched on various search strings based on their relevance to the inquiry. 66 documents written in English language were included and appraised through the Scale of the Assessment for Narrative Review Articles (SANRA) tool to avoid any risk of bias. The PRISMA 2020 checklist and flow diagram has been used to report the findings of this narrative review\n\nResult The study identifies eight critical parameters of CBE with respect to its definitions, origins, transitions, regulatory environment, characteristics, approaches and implications on teaching-learning, frameworks and models of assessment; and challenges, which makes a case for the relevance of CBE for architectural education in India, which hasn’t been explored yet.\n\nConclusion The broader expectations of ‘being competent’ can be addressed through a conscious adoption of strategies of relevant attributes of CBE which can encourage building attitudes and temperament for life-long learning",
"keywords": [
"Quality",
"Value",
"Life-long learning",
"Assessment",
"Knowledge integration",
"Accountability",
"Architectural education",
"Affective domain",
"Curriculum",
"Proficiency."
],
"content": "Introduction\n\nArchitectural education at its core, is a culmination of learning knowledge, skills, attitudes as well as values which are reflective of the challenges and possibilities of a genuine human experience, which eventually reflects in the quality of graduates. The evolution of architecture and its education, is an important professional strand of our environmental fabric as it is reflective of the possibilities of a genuine human experience, which eventually reflects the quality of graduates. As per the Charter for Architectural Education framed by the International Union of Architects (UNESCO, UIA, 2008), the main goal of architectural education should be to produce professionals who are intellectually mature, competent, ecologically conscious, socially responsible, and excellent world citizens.\n\nIn a globalized world, mobility between countries is increasingly desired, laying implicit expectations on the quality of education to be at least comparable, if not at par. The majority of professionals that one meets frequently lament that the average quality of fresh graduates they hire is drastically below what is required (Khan & Khan, 2019; Chandavarkar, 2018; Menon, 2017; Dua and chahal, 2014; Mehta, 2006). Such concerns highlight the questions on the qualitative aspects surrounding assessment of quality in learning of the graduates. While enough attention is given to various attributes which constitutes a technical architectural education, there is a need to define competence as an explicitly holistic part of the learning framework for assessment of learner’s outcomes. Assessment should not just be the driver, but it can also be a motivator for learning. The central research question of this study is to explore and identify the core aspects of Competency Based Education (CBE) are relevant for architectural education in India.\n\nCBE, as a formal process, is relatively new and not yet a widely practiced approach in the discipline of architecture in India. Citing differences between integral aspects of ‘thinking’ and ‘doing’ from a regulatory point of view, Prof. A. G. K. Menon (2017) points how vocationalising can create a divide between the two equally important aspects of the domain. With that rationale, he advocates the need to delink the licensing of architects from the process of education, to ensure quality of architects for practice, which requires specific competences. This is the norm in all developed countries and for the certification of this knowledge new systems must be developed (Menon, 2017). CBE has been explored in different capacities in different countries for a wide range of programs (Barman & Konwar, 2011; Bohain, 2018; Bernikova, 2017; Biemans, et al., 2004; Book, 2014; Ford, 2014; Nodine, 2016). The article presents the findings of a narrative literature review and identifies attributes of a CBE which makes it relevant for the education of architects in India. In its intent, the study also makes a case of how such steps can provide the initial foundations on bridging gaps in proficiency and quality when compared across the continents to produce world citizens in an effort to provide quality education for all.\n\nThis article is structured through following sections. After the brief introduction and problem statement, Section 2 provides a background to the inquiry of this research question through an overview of the existing literature specific to architectural education which outlines its current state and nuances from various realms of the field. Section 3 presents the methodological approach adopted for this study and the rationale behind its choice. Section 4 provides the results of the findings through a discussion of eight broad attributes of CBE from other fields of its current practices which can be related to the inherent requirements of architectural education. Section 5 concludes with a summary of challenges, strategies, relevant attributes of CBE, along with a note on future research directions derived from this understanding.\n\n\nBackground\n\nWith an aim to impart quality higher education, the National Education Policy 2020 echoes the objectives of UNESO and strongly advocates the need to develop good, thoughtful, well-rounded, and creative individuals (MHRD, 2020). The making of a professional like an architect, incrementally begins from a school education. As an acknowledgement of the same, the NEP 2020 envisages a significant shift in the educational ecosystem in India at all levels, where the focus has now shifted from ‘content’ to ‘competency’. It lays emphasis on a competency-based education right from the school environment and mandates to prepare students for the 21st century skills. It highlights the need for an assessment system that encourages real learning for real life context, where assessment becomes the driver and motivator of change in teaching quality in the classroom. This systemic shift in perspective must make a way towards higher education, and bridge that gap for architectural education as well.\n\nAs J. Mehta (2006) explains, Architectural knowledge and practice in India has been traditionally imparted and transferred through earlier generations in an informal manner, through apprenticeship and a master-pupil relationship. Before the beginning of a formal system of architectural education, the traditional and vernacular systems have prevailed. For the purpose of training artists and draftsman in reproduction of European classical arts, institutes like J.J. College of Architecture were opened in 1913, which introduced the initial model of formal and structured curriculum. The formation of institutions like Indian Institute of Technology, Kharagpur introduced a technological and scientific spirit. With such directions the utilitarian and problem-solving approaches began taking over some of the uniqueness of the profession which is a fusion of humanities, aesthetics and liberal arts (Mehta, 2006). While different schools of thoughts have indeed made various kinds of qualitative contributions towards the evolution of architectural education in India, it has largely remained a reduced extraction of its regulating frameworks mostly dominated by quantitative and technical aspects.\n\nArchitectural Education in India is governed by the Council of Architecture, a statutory body of the Government of India, through guidelines prescribed by ‘Minimum Standards of Architectural Education’. Ar. Habeeb Khan (2019) in his article, ‘Nemesis in the genesis: Reforming architectural education in India’ highlights how the Minimum Standards of Architectural Educational is effective in assessing the quantitative aspects, but for the lack of attention to qualitative aspects the education is suffering (Khan & Khan, 2019). While the standards allow ample room for institutions to develop their own curricular content as per their pedagogical ideologies, barring some of the notable educational practices most of the institutions revolve around adherence to the ‘minimum’ of broadly defined aspects. Studio and Theory are the two prime categories of coursework in architectural education. Institutions try to adopt their own methods of delivering content as per the opportunities and challenges pertaining to organization, resources, and above all, the nature of vision they keep as providers of education and its experience. The assimilation of acquired skills and knowledge is tested in the industry, where practitioners often voice a concern for the quality of graduates coming out of the educational domain (Chandavarkar, 2018). Apart from quantitative measures of performance, there aren’t any specific standard qualitative parameters which define or validate the quality of a learner’s progression. The conscious focus on the word ‘competent’, an explicit expectation of the Charter for Architectural Education (UIA), seems to be missing.\n\nExplicit development of qualitative aspects and an intentional emphasis on the affective domain is very important in acquiring abilities for a learner’s progression. There is a need for a focused approach towards planning and an intent towards execution of a coordinated teaching learning framework, through its curriculum and pedagogy, which explicitly aims towards identification and assessment of such competences, which can enable its development. The study of current state architectural education in India points towards gaps in how architects are educated towards acquiring the qualitative dimensions of learning, in the definition of quality in learner progression, in mechanisms for building students’ competencies effectively during their studies, and in the assessment of such abilities.\n\nLike any other professional field, the role of knowledge integration in architecture is very important. As described by A. Salama (2008a) the production of architecture takes place in the field of tension between reasoning, feeling, and instincts, as integral modes of being. The holistic idea of ‘building’ emanates from the conceptualization, coordination and execution of necessary abilities, while the act of building is rooted in humane tradition. Hence, the pedagogy for architecture must be focused towards manifestation of such integrations (Salama, 2008b). At the 2019 Pune (India) conclave of concerned practitioners, educationists, young professionals and others working in allied fields, gathered to contemplate how architecture today is disconnected from its ethical foundation of being the profession that accepts responsibility for the stewardship of built environment, and is mired in a self-absorbed pursuit of personal glory and material acquisition instead of offering widespread and equitable value to nature and culture (Conclave, 2021). Such voices reflect the state of values as perceived and practiced by the professionals and learners alike.\n\nAr. Prem Chandavarkar also points out, how we need to have a different mind-set to tackle the challenging demands of today’s rapidly changing environment and the need to produce professionally trained architects and designers (Chandavarkar, 2018). Being a professional field, the need to effectively demonstrate the acquired knowledge, skills, and attributes is extremely critical for a holistic sustenance of the built environment. Such training and response mechanism from the architects will require a conscious awareness of their strengths and weaknesses as individuals with certain capabilities. While exposure to obtaining such attributes must be inculcated beginning from the educational journey, their conception must be rooted in the awareness of the broader expectations from the profession. So, education and practice share a symbiotic relationship, as well as responsibility, where one of the prime focus for these two spheres has to be around the definition and development of the set of competencies required by an individual to make meaningful contributions to our built environment.\n\nViewed from outside of the academy as a social institution, education in post-industrial society is student centred, technologically enhanced, outcome driven, best-practice oriented, evidence based, and assessment validated. Hence measurable program learning outcomes become fundamental to the post-industrial/postmodern curriculum. Citing assessment as an ongoing activity which should aim at enhancement of the discipline, J. Mehta (2006) emphasizes on the need to create meaningful learning experiences and the role of systems based on competence as effective means to establish program coherence. Practices based on critical inquiry, self-discovery through reasoning and building empirical evidences of how learning is accomplished can also help institutions in mitigating the mounting pressure from accrediting agencies, government funding, employers and public sector, for accountability and transparency in educational systems which will eventually benefit the society as a whole (Mehta, 2006).\n\nAs pointed out by J. Mehta (2006), architecture is not merely a technical activity, but a value loaded activity, as it responds to the human needs and imaginations. Hence, the education of an architect and the curriculum it follows, must be much beyond the needs of the profession. It should not only provide for the basic competencies required by the discipline, it has an obligation to foster a culture of healthy criticism and ideation (Mehta, 2006). Ar. Prem Chandavarkar (2018), refers to skills as “a necessary but not sufficient condition”, stressing on the need to go beyond skills and explore the value-based propositions which enable critical thinking, to build attitudes and temperament for life-long learning (Chandavarkar, 2018; CSE, 2020). Hence, the need to address such gaps point towards a shift in the way education of an architect is conceptualized. It brings in focus the questions around the curriculum, and its integral structures which can facilitate the provision of such kinds of learning. To tackle such concerns, CBE has been widely used across the globe in different forms (Ford, 2014). Although the concept isn’t entirely new, the lack of one standard way of conducting it, presents a challenges of reference points, but also provides a unique opportunity to assimilate best practices for formulating educational structures which are focused towards conscious development of relevant competencies.\n\n\nMethods\n\nThe objective of this article is to explore integral aspects of a CBE from other disciplines to understand their potential relevance with architectural education in India and identify attributes of CBE, as an outcome, which can be relevant for architectural education in India. This narrative review approach follows a qualitative data analysis process, as described by Ritchie et al (Ritchie, Lewis, McNaughton, & Ormston, 2014). The following study design, data collection and data analysis method has been used to develop an understanding towards our research question.\n\nOwing to its limited or lack of adoption in field of architecture, there is a need to synthesize various aspects of CBE and integrate relatable experiences from various contexts and disciplines which have adopted it. Since such a practice is often domain-specific, such synthesis will require a nuanced understanding and description of qualitative interpretation of under-researched topics which can offer new insights and ways of thinking from robustly researched fields. In recognition of this need, a qualitative grounded theory approach (Charmaz, 2009) and a non-systematic narrative review methodology was chosen for gathering and synthesizing a broad range of complex information to develop an overview, which can pave path towards focused areas of further systematic inquiries and future research questions about important aspects of adopting competency-based systems.\n\nThe initial search started on 9th July 2022 using different keyword searches on multiple databases like Scopus, Google Scholar, ERIC, ResearchGate, Academia, Wiley Online Library. Considering the purpose of the study conference proceedings were also referred to gather a wide range of view from available research. The study included relevant literature which documented various fundamental aspects of CBE from the stand point of its conception, transition and execution. Since most of the documents broadly outlined more than one aspect the following concepts were derived as themes for the research question for making decisions around study selection; definition, origins, evolution, important milestones, characteristics, approaches and implications on teaching-learning, existing frameworks and models of assessment, challenges and criticism. Only full text documents were included for analysis.\n\nThe context of the search result extended to included findings from a range of multiple disciplines like Medical education, Engineering, Social Science, Vocational Training, etc. from different regions and countries like Europe, USA, Russia, United Kingdom, Australia and Korea where specific organizations and regulatory bodies have focused their works towards the defining specific competencies for their respective regions with a suitable supporting framework. Keeping in mind the evolutionary phases of competency-based systems, type of sources included all type of research documents such as journal articles, conference proceedings, essay, technical report and guides, published in English language between 2000 and 2022. Even though it is not mandatory for this non-systematic form of narrative approach, we have broadly tried to follow the PRISMA 2020 checklist to adhere to the effective measures of reporting and guide the research for avoiding bias as far as possible. Since the study does not intend to critically review the identified literature, we have not followed all steps of the PRISMA 2020 checklist.\n\nThe documents were collected in independent online searches towards the following five categories; Architectural Education and Pedagogy, History and Disciplines of CBE Overview of CBE, Frameworks and Assessment in CBE, Transition from traditional education to CBE. Articles were manually screened and shortlisted after reading full texts and sorting the findings in these five categories (Table 1). The selection of manuscripts for the review was to capture the broad aspects of CBE, instead of critical analysis of identified literature.\n\nComplete document files were independently studied by the three researchers. For appraisal of the included studies and to avoid the risk of bias, the Scale of the Assessment for Narrative Review Articles (SANRA) tool was used, which helped towards identification of the final full text included in the review (Baethge, Goldbeck-Wood, & Mertens, 2019). Content was thematically analysed in the five categories (mentioned above) to address the purpose of this study. SANRA is an open access tool and the document explaining its instructions can be found at: https://www.aerzteblatt.de/down.asp?id=22862.\n\nThe PRISMA 2020 checklist and flow diagram has been used to report the findings of this study (PRISMA, 2020) (https://www.equator-network.org/reporting-guidelines/).\n\n\nResults and discussion\n\nThe initial independent searches yielded a total of 313 documents in the 5 categories, i.e. Architectural Education and Pedagogy (n=56), History and Disciplines of CBE (n=51), Overview of CBE (n=62), Frameworks and Assessment in CBE (n=66), Transition from traditional education to CBE (n=78). After title screening 46 documents were excluded and a total of 267 document were retained for further screening. After screening of abstracts, 137 documents were excluded, and 130 documents were sought for full text reading. After screening through full reading stage, 66 documents were found eligible for the purpose, and were included in this narrative review. i.e. Architectural Education and Pedagogy (n=02), History and Disciplines of CBE (n=37), Overview of CBE (n=11), Frameworks and Assessment in CBE (n=09), Transition from traditional education to CBE (n=07). The results are presented below in a flowchart following the PRISMA 2020 template (Figure 1), and a summary of the included studies has been presented in Annexure 1.\n\nThe included literature finds its origin in different disciplines and regions between a timeline of 2000 to 2021, with a wide range of purpose in the focus of its documentation. The type of documents included are Articles (n=49), Book (n=1), Case Study Document (n=1), Reports (n=7), Essay (n=1), Reference Documents (n=5), University update (n=1), call for paper (n=1). Most of the information comes from the field of Medicine (n=21) and the least from vocational fields (n=2). We could find a few relevant documents from the discipline of Architecture (n=4). Geographically, majority of the included literature comes from USA (n=36), India (n=7) Canada (n=4), while others combine from Russia, Canada, Netherlands, Australia & New Zealand. While the CBE has been in contention earlier than 2000 as well, there has been a surge in the perception of its relevance since 2010. Of the identified literature, 10% comes from a timeframe between 2000-2010, while the remaining 90% is spread out between (2010-2021), with a consistent and continuing rise in such publications.\n\nThrough a broader understanding of the several critical parameters discussed in the literature collected in 5 categories, we could observe a presence of 11 different themes (Table 2) across these documents, like; (a) Discussion of key concepts (n=39), (b) Definitions (n=21), (c) History & Origins (n=16), (d) Regulatory environment (n=11), (e) Gaps and Challenges (n=11), (f) Characteristics and Principles (n=30), (g) Transition points (n=9), (h) Implications of Teaching and learning (n=19), (i) Assessment frameworks and models (n=25), (j) Future directions (n=13), and (k) Criticism on CBE (n=8).\n\nThe findings have been synthesised and presented here as a narrative in 8 themes which reflects the overview on the current state of knowledge of CBE with respect to its; (1) Definitions from different contexts, (2) History: origins and transition from traditional to CBE, (3) Transitions, (4) Regulatory environments, (5) Characteristics, (6) Approach and implications on teaching and learning, (7) Assessment frameworks and models, and (8) Challenges and Criticism. These segments aim to capture some of the key ontological and epistemological concepts which can `provide the necessary rationale leading towards the understanding of CBE, and its potential relevance to architectural education in India.\n\nA “skill” is about doing something well, “Knowledge” is the known information, and an “attribute” is an inherent quality and is often expressed through what you think, do and feel. Together, these three elements make up a competency. Competencies are expressed in ways that can be observed, measured, associated with different real-life environments, transferred and are performance-based. To understand competence/competency, from an educational perspective it is equally important to inquire upon the notions of the word curriculum. It derives its root in the verb ‘currere’ in Latin. The meaning of the word involves connotations of ‘movement’ and ‘journeys’. R R Burns, in his article, explores the entomological roots which explains a deeper understanding of the word curriculum. Curriculum can also be related as a journey to the places one may not think are important, but gathers significant experiences as a result of its dynamic socio-temporal nature which is embodied in the time, space and the manner in which that time is spent (Burns, 2020). Spady (1977) in his article, summarizes the approach called ‘competency-based education’ where he emphasizes on the need to build suitable mechanisms to facilitate appropriate diagnosis of weaknesses and remediation.\n\nDefining ‘competency’ and an ‘educational competency’ is a complex challenge. As per PISA (Program for International Student Assessment), it is more than knowledge or skill. It is more about developing abilities to meet complex demands. Irina A Kedrova, in her research, explains a Russian perspective through the words of A.V. Khutorsky (2004) who understand competency as an individual’s preparedness to apply the knowledge, skills and external resources for enabling effectual actions in certain life situations (Kedrova, 2016). In United States of America, CBE is perceived in terms of having focus on learning outcomes, instead of time spent in a classroom (Education, 2015). Competency is concept related to a person, while competence is a concept related to work (Armstrong, 2005). The definition of competencies can vary as per interpretation and context as it needs to assess critical human characteristics as “quality”, “character”. Competence is a holistic concept which reflects an individual’s capacity and abilities to perform effectively (Ten Cate & Scheele, 2007; Ford and Meyer, 2015). A model of professional competence can be categorized into five types; (a) Cognitive, (b) Functional, (c) Personal, (d) Ethical, and (e) Meta-competence. In contrast to the work done by Russian and Kazakh scientists, other scholars have focused on the practical orientation of this issue (Makulova, et al., 2015).\n\nArchitectural practice embodies process, organization, business, conviction. Apart from focusing on the products of the practice, Architects engage with the contradictions between responsibilities of ethical nature and bearing accountability towards the stakeholders, the challenges of the practice and intricacies of architectural imagination, the aesthetical and imaginative foundations of the field makes it incumbent upon the architects to possess ecumenical proficiencies and knowledge, which largely points towards the broader expectations of being ‘competent’. In its most basic form, competence is the quality of being competent, while competition is the act of competing. The word competency also derives its roots from the Latin word competentia, which means “meeting together, in agreement and symmetry” (Seng, 2021).\n\nOutcome Based Education (OBE) which defines learning in terms of outcomes can be considered as the precursor to CBE. Beginning with its roots in behaviourism, different authors have mapped the evolution of CBE in terms of its societal and theoretical origins. The development of competency-based approaches can be understood outside of the realm of education and training through practices like craft guilds, apprenticeship, etc., where criteria for competence and performance have been defined and developed for certain vocations and positions (Nodine, 2016). As a society, even as the idea of competency has existed since over a century, according to Houston (1974) CBE has evolved as a cultural trend towards ‘accountability’ and ‘personalization’ in American societies. As a political catalyst, a range of commentators also credit the development of CBE to the effects of the launch of Sputnik on the American imagination, which triggered an educational reform in the America. The passing of National Défense Education Act in 1958 has been seen as the first formal step which emphasized on mastery in education and training. Another stimulus was the enactment of the Vocational Education Act in 1963. It triggered development of educational models which were characterized by ‘the precise specifications of competencies’. The Elementary Teacher Education Models (1965) a program of the United States Office of Education (USOE) formulated the Performance-based Teacher Education (PBTE) movement (Hodge, 2007).\n\nTheoretically, the fields of behavioural psychology and systems theory have important influences on the origins and development of CBE. As mentioned by Hodge (2007), most of the psychologists who worked towards the problems of efficient training in the United States military had a behavioural premise. They worked with the rationale that our knowledge is ultimately built on our sensory experience. In 1913 the American scientist John B. Watson aimed to study human psychology strictly in terms of observable behaviour. Descartes’ theory, identifies the necessary connection (reflex) which exists between a given external influence (stimulus) and the resulting reaction (response). Contributions by Thorndike (1911), Pavlov (1927), Skinner (1953) in terms of theories on behaviourism have positively influenced the general approach of CBT. Bertalanffy (1968), Gagné (1962) and Crawford (1962) through their philosophies on Systems Theory emphasized on the inter-disciplinary amalgamation (Hodge, 2007). Traditionally, for the eventual purpose of application, the studio-based learning philosophies and the hands-on approach has dominated the knowledge generation and integration for learners in the field of architecture. The interdisciplinary nature of architectural practices, has always drawn attention towards the learnings of cause-and-effect principles and interpretations from different fields to expand its horizons which have a far wider impact on human condition. Since the intention of CBE is focused towards development of individual characteristics for betterment of outcomes, a lot can be learnt from such practices in the future course of its evolution.\n\nThe programs following a CBE approach in American higher education can be classified in following three phases: (a) Teacher Education programs (1960s onwards); (b) Vocational Training and Education programs (1970s onwards); and (c) more recent “Direct Assessment” programs as Online or Hybrid models, which have been propelled by the advances in adaptive learning technology. Programs offered by Western Governors University and other such institutions, can be seen as part of the latest phase in the development (Nodine, 2016). In its transition CBE has followed different approaches in different regions, where the key differences have emerged in terms of the ‘form of education’ and its ‘content’ (King, 2021). The approaches adopted in USA have typically meant flexible, personalized, self-paced, skill-based education. Whereas the other approach spread across Europe and Russia are associated with the Bologna System of Higher Education, which comes from the Bologna Process (Bernikova, 2017).\n\nTransitioning from a traditional studio and apprenticeship-based practices and in view of the regulatory environment, the scale of architectural education in India has encouraged several institutions to turn to Outcome-based Education (OBE) model. While keeping its focus on the outcomes, CBE redefines and prioritizes the nature of learnings in terms of acquisition of competencies as the indicator of the outcome, which are not just intended to be more observable, but also measurable so as to enable the adoption of tangible practices towards development of such attributes which promote life-long learning.\n\nIt is important that the regulatory bodies develop supportive regulatory formats which meet the needs of competency-based programs (Cunningham, et al., 2016). As explained by Nodine (2016), in the US higher education ten institutions were chosen to initiate CBE in 1968 to provide training programs for elementary school teachers. These pilot programs, which also represents the initial competency-based models for higher education, aimed towards improving quality of aspects related to teachers. In 2013 the Experimental Sites Initiative (ESI) program, issued a reference manual on CBE to make using federal student aid for such programs easier (Nodine, 2016).\n\nCBE began to gain more prominence with the development of Western Governors University (WGU) in 1995. Alverno College (1970s), Thomas Edison State (1980s), Charter Oak State College (1990s) and Southern New Hampshire University’s College (2000s) are some of the other programs known CBE programs. As Sasha Thackaberry highlights, how the Higher Education Act in 2005 made it possible for “Direct Assessment” programs. Southern New Hampshire University (USA) was the first college approved with this option in 2013. (Thackaberry, 2016a, 2016b) Several voices in India call upon the need to build on the qualitative aspects of architectural pedagogies and assessment of learning. The instances from other fields and countries highlight the critical role played by the regulatory environments in this regard, which can turn out to be the catalyst for change. The need to recognize the far-reaching benefits and consequences of programmatic assessment are paramount. NEP2020 opens up new avenues for the same.\n\nAs explained by McGaghie, an educational program’s goal is competence, and a curriculum provides the means by which competence is to be attained (McGaghie, et al., 1978). A competency-based approach is focused towards principles of personalized and mastery learning, where the development and characterization of competencies is expected to be career relevant, professionally broad and specific to an attribute (Cunningham, et al., 2016). Several authors have elaborated the various descriptions and characteristics of competencies and CBE. With reference to the medical field, Olle Ten Carte and Stephen Billett explain how context facilitates and often determines the translation of knowledge into its enactment. Competencies can be looked at as the will to use the canonical knowledge in situational environment (ten Cate & Billett, 2014). Patricia A. Book (2014) in her report “All Hands on Deck: Ten lessons from early adopters of competency-based education” captures snapshots of the experiences from seven competency-based post-secondary programs and reflect from their exemplary work (Book, 2014). Malulova et al. explains how the components of the “four pillars of education” by Jacques Delors serve as the pre-requisites for competency and competency-based approaches (Makulova, et al., 2015).\n\nHaris Saud and Ruth Chen (2018) in their integrative literature review cite observations by Lawrence Stenhouse who argued that it is not possible to develop values, understanding, and judgement solely through behavioural goals. Even if assessment of the affective attributes can’t always be objectively performed, they are equally important (Saud & Chen, 2018). Such characteristics and attributes are integral to the objectives and expectations from learners of architectural education. With the classification and categorization of the nature of competencies, the overall aim of developing individual capabilities in a holistic manner remains the ultimate goal of CBE as well. Context-relevant criteria for learner performance and methods of assessment can be developed through appropriate methodologies for architectural education in India to enhance the awareness towards the necessary means and approaches for attaining it.\n\nIn CBE the teacher is supposed to adopt a coaching role who guides the learning processes for a student. The responsibility of learning belongs to the learner, while it must be facilitated by the instructor. This transition requires a paradigm shift in perceptions and attitudes from both stakeholders (Clarke, 1990; Biemans, et al., 2004). As the initiators of this approach, the value of faculty willingness and training is an integral aspect in the course of development of CBE. Nadia Serdenciuc has enlisted a range of abilities that would be relevant as a possible teacher’s profile from a CBE perspective (Serdenciuc, 2013). Steven Hodge (2007) in his article cities Kornhauser (1922) who made a number of recommendations to reform apprentice training while educational theorist Carroll (1963) provided the first complete model of mastery learning. Realizing its potential, Bloom (1956) built on this model by identifying five factors which each mastery strategy must deal with; (1) Aptitude, (2) instructional quality, (3) How one understands instruction, (4) Persistence, and (5) Learning time. Bloom’s advocacy of mastery learning represents a humanist contribution to CBT (Hodge, 2007).\n\nKate Ford in her technical report has identified the Degree Qualifications Profile (DQP) by Lumina Foundation’s as one of the important learning frameworks which outlines educational outcomes in terms of what graduates should know and can do. The DQP focuses on specific learning areas to organize the competencies of a program (Ford, 2014). For a learning to reach a specific level of performance it is important to know and map how one can get there. Lockyer et al. (2017) have discussed the importance of Miller’s (1990) contribution who related the four levels of learning as a represented in the form of a pyramid. Beginning with what the learner “knows,” the hierarchy then proceeds through levels of “knows how” and “shows how” before reaching the highest level, “does” (Lockyer, et al., 2017). Jeremy Branzetti et al. (2019) attempt to focus beyond the notions of competency and its assessment, saying it is equally important to adopt a focused and a meaningful approach towards curriculum design. According to him, curriculum can be a mitigator to assessment. Fink’s model of taxonomy and its six domains, as learning areas, could be an effective way to achieve this outcome instead of the widely used Bloom’s taxonomy (Branzetti, et al., 2019). Figure 2 explains the 6 domains of fink’s taxonomy of significant learning. These domains can be understood for its relevance with architectural education as well.\n\nAs Wiggins (1998) says, the aim of assessment should be to improve performance of the student instead of merely auditing it (Wiggins, 1998). The relevance of content-referenced measures of performance assessment in CBE has been strongly explained and established by various educators and scholars. Glaser (1962) has proposed that the testing should indicate whether the students have developed the ‘behavior’ expected or intended in the design of the coursework (Glaser, 1962). Citing a case of the medical field, Norcini (2005) explains how higher order assessment would require direct observation, structured feedback on performance or skill-based evaluation is simulated on real patients (Norcini, 2005; Norcini & Burch, 2007; Cate and Regher, 2018). Dilmore et al. (2013) in their article describe the CBE Framework Development for a Clinical and Translational Science Institute (CTSI). As a certificate and degree-granting program, they followed the incorporation of the following three steps in their structure; (1) Curriculum Development, (2) Curriculum Alignment, and (3) Curriculum Support. Lomisa et al. (2017) recommend the framework of ‘Milestones’ which are “criterion-referenced” set of performance benchmarks.\n\nThese can be applied to various programs, courses and settings. It can improve the process of trend identification and allow stronger evidence to be generated which can in turn prompt the student to act (Lomisa, et al., 2017). The Entrustable Professional Activities (EPA) Framework, developed by Olle ten Cate for programs in the medical field, is becoming a widely accepted framework. It leads to recognizable outcomes which are expected by the community from the competent professionals. It includes a list of competencies and in totality they encompass a given domain (Ten Cate & Scheele, 2007; Gruppen, et al., 2016). Dwijendra, in his research article which captures aspects of learning around architectural education in Indonesia, cites the case of UIA, where high-performance standards of professionalism are used by UIA to describe an architect’s professional capabilities. Figure 3 shows these requirements which include 13 fundamental professional knowledge and abilities of UIA international standards, 3 mastery levels, and 37 items (Dwijendra, 2021).\n\nSource: UIA. (2007a). Thirteen Basic Knowledge and Professional Skills of UIA (International Standard). International Union of Architects. Retrieved from: https://www.uia-architectes.org/webApi/en/. UIA. (2007b). UIA Architectural Professionalism Performance Criteria. International Union of Architects. Retrieved from: https://www.uia-architectes.org/webApi/en/\n\nMany institutions and alternative educational providers are exploring the intricacies of developing a CBE programs. An article by A. Sasha Thackaberry outlines how the increasing sophistication of CBE programs has largely been possible due to technological improvements. (Thackaberry, 2016a, 2016b) The ACGME refers to the Dreyfus Model (1986) to outline competencies for its programs which require guidelines on methodology training. Hubert and Stuart Dreyfus, who were assigned by the U.S. Air Force, came up with the concept to explain how a pilot’s knowledge and abilities grow. This model, has five levels of proficiency (Figure 4), in an increasing order of mastery learning which can be referred as milestones of a learner’s progression (Sultan, et al., 2019).\n\nFor implementing a mastery approach educational institution need to clearly communicate the expectations of mastery and levels of achievement and identifying ways in which students can demonstrate such proficiency or mastery (Nodine, 2016). All competency-based programs are different and hence it poses a challenge to accreditors. From a secondary school education perspective, teachers have felt that competency-based assessments forces them into endless cycles of assessment and that deciding the levels of achievements as well as the design of assessment instrument have been difficult tasks. This also points towards the challenges associated with building a pool of skilled and dedicated faculty which can train and assess the level of competency in a trainee (Clotilda, 2021; Pitman, et al., 2000; Oroszi, 2020).\n\nBased on the observations from the current literature available, Hoang and Lau (2018) have identified “Reductionism” and “loss of authenticity” as critical challenges for developing the curricular structures and corresponding assessment tools (Hoang & Lau, 2018). The literature on CBE points towards a different kind of engagement by faculty, most importantly in the domain of willingness. Ford highlights how the described changes in traditional faculty roles, have resulted in the faculty themselves being some of the chief critics of CBE (Ford, 2014). In a literature review of documents published between 1966 to 2002, Carraccio et al. (2002) observed that application of competency-based models to medical education often end up being stalled at the conceptual level (Carraccio, et al., 2002).\n\nErnest L. Boyer, then-president of the Carnegie Foundation for the Advancement of Teaching, during his lecture in 1993, urged educational systems to move beyond the old Carnegie units as the learners still fail to acquire a more encompassing view of knowledge and life. As Cunningham et al. (2016) emphasizes, the development of CBE programs must focus upon formulating process towards practicing alignment, strengthening validity, defining faculty roles and supporting students through the assessments (Cunningham, et al., 2016). Citing the Cleveland Clinic Lerner College of Medicine, who decided to change the system of grading medical students, focused on developing appropriate performance standards, Olle ten Cate roots for the use of “narrative description” with relevant behavioural milestone descriptions, which can be converted into a 9-point scale (ten Cate & Billett, 2014). Citing Hattie and Timperley (2007), Peter Bohain (2018) highlights the importance of ‘feedback’ on assessment tasks, and a need to reduce the emphasis on grades or marks as they contain little information about improvements that can be brought about for reaching the learning goals (Bohain, 2018).\n\nCompetency-based evaluation can make a significant contribution to finding, choosing, and developing brilliant people (van der Merwe, 2002). Based on how candidates actually perform in their allocated job positions, the assessors judge whether candidates meet the predetermined competency standards during the assessment process (Gonczi, 1994). Conducting a good competency-based evaluation, however, is difficult (Suhairom, et al., 2014). First of all, not all competencies can be seen in plain sight. Second, certain commercial organisations or professions have very broad and diverse job responsibilities. Making sound judgements has become challenging as a result. In order to precisely and successfully estimate an individual’s competency levels in carrying out particular jobs and duties, evaluation methods as well as the assessors, must be thoughtful and dynamic (Baartman, et al., 2006; Clary et. al, 2011). Additionally, sufficient evidence of performance, both in terms of quality and quantity, must be gathered in order to make accurate assessments (Gonczi, 1994; Lee, 2018). The assessment and improvement of competencies is a continuous process. For the purposes of competency assessment, the created competency information must be properly arranged and presented. A competency typically has three parts: a definition of the competency title, an explanation of the visible behaviours that can be utilized to show competency mastery, and a thorough discussion of the skill’s performance levels (Campion, et al., 2011). The process of defining competencies is a rigorous process which requires awareness and complete involvement of the faculties, since they need to be aligned with the finer aspects of learner progression.\n\nThe objective of this article is to explore integral attributes of a CBE from other disciplines to understand their potential relevance to various challenges facing architectural education in India. Table 3 summarizes the various challenges of its context as aspects of the eight domains of this study, and attempts to provide a broad map of directions and outcomes which can be incorporated through the learning offered by the attributes of CBE.\n\nThe research study focused on understanding broad aspects of competency-based education and its relevance to architectural education in India through a non-systematic form of narrative approach. Performing critical analysis of the identified articles was not the intention of this study, so we may have missed out on capturing some aspects of this study.\n\n\nConclusion\n\nCompetency-based education (CBE), as a cultural trend towards accountability and personalization, is a systemic change and it requires a shift in perception and attitudes from all stakeholders. It can be a disruptive advance in higher education and the literature review points towards the following outcomes as strategies to be adopted. It requires programs to coordinates academic content and its delivery according to competencies, instead of conforming to conventional systems. CBE, at its core, envisions curriculum as a journey which can enable diagnosis of weakness and remediation, aspires to recognize and encourage better preparedness. With a prime objective of promoting mastery learning, CBE calls for coherent definitions of competency statements and development of qualification profiles for architectural education. Learner progression needs to be explicitly outlined though a system of milestone which embody the core characteristics of innovative teaching-learning models.\n\nStrategies in terms of practices like ‘Competency Portfolio’ as “the transition to competency” is one of the key exemplars towards understanding different measures for developing a CBE environment. Expert judgment, which includes subjectivity, is unavoidable in discipline like architectural education, and it is a quality which can increases with experience. The validity of context dependent activities and subjective judgements must find a place in the process of assessment, which has also been echoed by frameworks like Milestone development, levels of learning and Entrustable Professional Activities (EPA). Currently medical education in India has already begun to evolve its systems along the lines of CBE. Such measures demand experimentation, process orientation, dedicated involvement from educators, a radical rethinking in the manner of outlining our educational goals and intentions for developing the means to achieve them. The frameworks of assessment need to be dynamic and holistic in nature to provide a meaningful sense of feedback which promotes true lifelong learning and emphasizes development of an individual character.\n\nFuture direction could revolve around development of context-relevant criteria for learner performance and methods of assessment can be explored through appropriate methodologies for architectural education in India. CBE brings about structural changes in the educational environment which requires active involvement and coordinated participation from the entire team of instructors as a beginning towards knowledge integration and an attitudinal change in academicians is required to provide a better coordinated learning and assessment of affective attributes in terms of content, process and environment. Since the competency approach in education is still evolving, incorporation of such systems will mean a conscious and sensitive assimilation of the experience from different environments for a contextual application, along with the attributes of the NEP 2020 in India.",
"appendix": "Data availability\n\nThe authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.\n\nThis research article has followed a narrative review method and has adhered to the PRISMA 2020 reporting guidelines, as far as possible. The corresponding PRISMA checklist (word document), and flow diagram (word document), has been included as the underlying data. Figshare: Checklist for PRISMA_2020_checklist (RCBEAEI), https://doi.org/10.6084/m9.figshare.26023858.v1.\n\nThe summary of articles included for study (Annexure 1).\n\nThe SANRA appraisal data (Annexure 2) has been included as the supporting material in the form of extended data (word document and excel sheet). SANRA is an open access tool and the document explaining its instructions can be found at: https://www.aerzteblatt.de/down.asp?id=22862.\n\nThese files can be found in the Figshare repository under the project titled ‘Relevance of competency-based education for architectural education in India’, with DOI: https://doi.org/10.6084/m9.figshare.26023858.v1, Licence: CC0.\n\n\nReferences\n\nHoang NS, Lau JN: A Call for Mixed Methods in Competency-Based Medical Education: How We Can Prevent the Overfitting of Curriculum and Assessment. Acad. Med. 2018; 93(7): 996–1001. PubMed Abstract | Publisher Full Text\n\nArmstrong M: A Hand Book of Human Resource Management Practice. 9th Edition.Kogen; 2005.\n\nBaartman L, Bastiaens T, Kirschner P, et al.: The wheel of competency assessment: Presenting quality criteria for competency assessment programs. Stud. Educ. Eval. 2006; 32: 153–170. 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}
|
[
{
"id": "307236",
"date": "19 Aug 2024",
"name": "Fadzidah Abdullah",
"expertise": [
"Reviewer Expertise architecture education"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. The research is very good and comprehensive. it shows the researcher has done very deep investigation. 2. However, the researcher did not really explain why there is a need to transfer from Content Based to competency based. In fact, competency could NOT be earned in architecture school alone, it would be earned more during the practice. Whilst, content based is easier as we could complete the syllabus on time based basis. Another point, experience in practice is very important to show one's competency. Meaning, investigating Competency could not be comprehensively investigated within the campus environment. 3. The identified 8 themes may help us to understand the current scenario, but each day there are new innovation that requires arch schools to move forward continuously. Something that is moving is very difficult to measure both qualitatively and quantitatively. 4. Hence, having this research regarded as narrative is very smart because it is very difficult to draw a conclusion. Therefore, result would depends on one's interpretation. 5. However, author has introduced a new term,\"context based\". This should not be the conclusion as if running away from giving solution to CBE. 6. I would suggest the author to omit any mention of context based education.\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? No",
"responses": [
{
"c_id": "12746",
"date": "11 Nov 2024",
"name": "Nikhil Kohale",
"role": "Author Response",
"response": "IN RESPONSE TO COMMENTS FROM REVIEWER 1 (Mr. Fadzidah Abdullah, Malaysia) Comment 1: Explain why there is a need to transfer from Content Based to competency based. Response: Apart from the overall discussion, a brief explanatory text has been added in the introduction segment. Comment 2: Author has introduced a new term, \"context based\". This should not be the conclusion as if running away from giving solution to CBE. I would suggest the author to omit any mention of context based education Response: The term ‘context-based education’ has been omitted. Although, the word ‘context’ has been retained/ used as an explanation for a larger narrative supporting competency based education (CBE), wherever necessary."
}
]
},
{
"id": "325164",
"date": "26 Sep 2024",
"name": "Jayendira P Sankar",
"expertise": [
"Reviewer Expertise The current research interests include Development Economics: economic growth",
"poverty",
"inequality",
"market failure",
"fiscal",
"economic and social condition",
"healthcare",
"education",
"employment sector",
"industrial and social infrastructure",
"Human Resource Management: employee welfare",
"work-family balance",
"consumer behaviour",
"retail marketing",
"corporate social responsibility",
"sustainability",
"and teaching-learning and assessments."
],
"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\nRelevance of Competency Based Education for Architectural Education in India Dear Editor, Thank you for giving me the opportunity to review this article. While the article appears complete,My initial question is whether it should be classified as a research article or a review article. Based on my understanding, it falls under the category of a review article, though the final classification is determined by the platform's guidelines. 1. The details provided in the introduction, background, methodology, and results sections are acceptable. However, there is a need to separate the discussion, implications, and suggestions for future studies into distinct sections.\n2. While it is understood that the study's timeline covers the period from 2000 to 2021, the authors could strengthen their findings and implications by including relevant studies from 2022 to 2024. This would help provide more up-to-date support for the conclusions.\nKindly follow the structure. 1. Introduction- provides background, states the research's purpose, discusses previous research leading up to the study, and may state a hypothesis or question. 2. Literature review- describes the publication, a summary of the publication’s main points, a discussion of research gaps, and an evaluation of the publication’s contribution to the topic.\n3. Method or Methodology- describes how the research was conducted, with details about the study sample, assessment measures and procedure.\n4. Results or Findings- a summary of the findings presented in text or table format may have individual sections with specific information.\n5. Discussion, Comments or Conclusion-explains how the results answered the research question and may suggest future areas for research.\n6. References- a listing of works cited by the author(s).\nIn my opinion, the article already contains sufficient information. The author(s) simply need to organize it more effectively to enhance its overall appeal.\nI request the author(s) to address the above comment.\nThe editor may accept the article for indexing, provided that the aforementioned comments are adequately addressed.\nAll the best\nThanks, and Regards\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? 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": "12747",
"date": "11 Nov 2024",
"name": "Nikhil Kohale",
"role": "Author Response",
"response": "IN RESPONSE TO SUGGESTIONS/COMMENTS FROM REVIEWER 2 (Mr. Jeyendira P Sankar, Bahrain) Comment 1: While the article appears complete, my initial question is whether it should be classified as a research article or a review article. Response: Our intended research article has followed a narrative review approach. However, for clarity and based on the observation/ suggestion made, we have now formatted the same as a review article as per the suggested structure within the journal format. Comment 2: While it is understood that the study's timeline covers the period from 2000 to 2021, the authors could strengthen their findings and implications by including relevant studies from 2022 to 2024. This would help provide more up-to-date support for the conclusions. Response: While restructuring the overall article, we have now included observations from relevant studies between 2021-2024 in appropriate sections as advised. Comment 3: Kindly follow the structure. 1. Introduction- provides background, states the research's purpose, discusses previous research leading up to the study, and may state a hypothesis or question. 2. Literature review- describes the publication, a summary of the publication’s main points, a discussion of research gaps, and an evaluation of the publication’s contribution to the topic. 3. Method or Methodology- describes how the research was conducted, with details about the study sample, assessment measures and procedure. 4. Results or Findings- a summary of the findings presented in text or table format may have individual sections with specific information. 5. Discussion, Comments or Conclusion- explains how the results answered the research question and may suggest future areas for research. 6. References- a listing of works cited by the author(s). Response: We have now followed the Review template as provided by the Journal, and incorporated the advised structure. It can be seen in the update version in the overall document. Comment 4: The article already contains sufficient information. The author(s) simply need to organize it more effectively to enhance its overall appeal. Response: We have restructured and reorganized the overall content, while adding new findings from recent publications as well, to increase its overall appeal. Comment 5: The editor may accept the article for indexing, provided that the aforementioned comments are adequately addressed. Response: We hope that we have incorporated all comments in the overall narrative of the article as per your suggestion, for enhanced clarity and towards gaining approval."
}
]
},
{
"id": "307235",
"date": "24 Oct 2024",
"name": "Ngakan Ketut Acwin Dwijendra",
"expertise": [
"Reviewer Expertise Architecture",
"Education"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nComments and Suggestions for Improvement\nLiterature Review: The literature review is comprehensive but could be enhanced by including more recent studies on CBE, particularly those published after 2020. This would provide a more up-to-date perspective on the topic. Methodology: The methodology section could be expanded to include a more detailed description of the inclusion and exclusion criteria for the reviewed documents. This would improve transparency and allow for easier replication by other researchers. Data Availability: Ensure that all supplementary materials and data mentioned in the article are accessible to readers. This could involve providing direct links to the datasets or ensuring that they are available in an open-access repository. Citations: Review and update citations to include more recent and relevant studies. This will strengthen the article’s foundation and provide a more current context for the discussion. Discussion and Implications: The discussion could benefit from a more in-depth analysis of the potential challenges and limitations of implementing CBE in architectural education. Addressing these issues would provide a more balanced view and prepare educators for potential obstacles.\nPoints to Address for Scientific Soundness\nClarify the criteria for document inclusion and exclusion in the narrative review. Ensure all supplementary materials are accessible and clearly referenced in the article. Update the literature review with more recent studies to reflect current trends and practices.\nConclusion The article makes a valuable contribution to the discussion on integrating CBE into architectural education in India. By addressing the points mentioned above, the authors can enhance the clarity, robustness, and impact of their work. Overall, the study is well-conceived and provides a strong case for the relevance of CBE in this context.\nRecommendation: Partly This assessment acknowledges the article's strengths while highlighting areas for improvement to meet the highest standards of academic rigor and transparency.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12748",
"date": "11 Nov 2024",
"name": "Nikhil Kohale",
"role": "Author Response",
"response": "IN RESPONSE TO SUGGESTIONS/ COMMENTS FROM REVIEWER 3 (Mr. Ngakan Ketut Acwin Dwijendra, Indonesia) Dear reviewer, Thank you for your feedback and suggestions. Sharing our response to the revisions/updates we have introduced in the updated/revised version (v2). Comment 1: Literature Review: The literature review is comprehensive but could be enhanced by including more recent studies on CBE, particularly those published after 2020. This would provide a more up-to-date perspective on the topic. Response: While restructuring the overall article, we have also included a few more relevant observations from studies between 2021-2024 in appropriate sections as advised in v2. Comment 2: Methodology: The methodology section could be expanded to include a more detailed description of the inclusion and exclusion criteria for the reviewed documents. This would improve transparency and allow for easier replication by other researchers. Response: We have attempted to restructure the overall methodology to provide more clarity by expanding the inclusion and exclusion criteria for the reviewed documents. Comment 3: Data Availability: Ensure that all supplementary materials and data mentioned in the article are accessible to readers. This could involve providing direct links to the datasets or ensuring that they are available in an open-access repository. Response: All supplementary materials and data mentioned in the article are accessible to readers through a digital repository. The accessible link is included in the data availability statement. Comment 4: Citations: Review and update citations to include more recent and relevant studies. This will strengthen the article’s foundation and provide a more current context for the discussion. Response: All relevant studies, including the newly added ones between 2021-2024, have been cited and referenced. Comment 5: Discussion and Implications: The discussion could benefit from a more in-depth analysis of the potential challenges and limitations of implementing CBE in architectural education. Addressing these issues would provide a more balanced view and prepare educators for potential obstacles. Response: The overall discussion section has been restructured to include extended discussion on challenges and a separate segment on implications, where we have attempted to provide a more in-depth analysis of the potential challenges and limitations of implementing CBE. Comment 6: Clarify the criteria for document inclusion and exclusion in the narrative review. Response: We have attempted to restructure the overall methodology to provide more clarity by expanding the inclusion and exclusion criteria. Comment 7: Ensure all supplementary materials are accessible and clearly referenced in the article. Response: All supplementary materials and data mentioned in the article are accessible to readers through a digital repository (figshare). Comment 8: Update the literature review with more recent studies to reflect current trends and practices. Response: Updated. We have tried to address the concerns you have shared. Hopefully it would meet approval. Regards."
}
]
}
] | 1
|
https://f1000research.com/articles/13-835
|
https://f1000research.com/articles/13-1348/v1
|
11 Nov 24
|
{
"type": "Review",
"title": "Ethiopia's Potato Seed System: Regulatory Challenges, Quality Assurance Issues, and Pathways for Improvement ─ A mini review",
"authors": [
"Lemma Tessema",
"Ebrahim Seid",
"Ebrahim Seid"
],
"abstract": "Background Ethiopia’s potato seed system is currently hindered by a disjointed regulatory framework, insufficient quality assurance processes, and a lack of collaboration among stakeholders, which collectively impede agricultural productivity and food security. The regulatory environment is characterized by inconsistent seed certification practices and a dependence on informal seed sources, negatively affecting the quality of potato seeds available to farmers. Although potatoes play a crucial role in global food security by providing high yields compared to other staple crops, the sector grapples with significant challenges due to bureaucratic inefficiencies, limited technical expertise, and the widespread presence of counterfeit seeds throughout the value chain.\n\nMethods To tackle these challenges, this mini-review outlines potential improvements, stressing the necessity for a unified regulatory framework tailored to the unique issues of vegetatively propagated crops. For this reason, we have used different literature source from web of science, Pubmed, Google Scholar, ResearchGate and other scientific websites. We have documented the most relevant information focusing on potato seed system, regulatory frameworks, quality assurance bottlenecks and pathways for improvement across the seed value chain.\n\nResults our paper highlights key recommendations that includes enhancing training for regulatory staff, investing in research for disease-resistant varieties, and bolstering public-private partnerships to encourage innovation and resource sharing. Furthermore, improving traceability in the seed supply chain is essential for maintaining seed quality and integrity.\n\nConclusions This review calls for a comprehensive strategy that fosters stakeholder engagement and promotes sustainable practices to rejuvenate Ethiopia’s potato seed system, thereby supporting the livelihoods of millions of smallholder farmers and strengthening national food security through integrated seed sector development and capacity improvement of the seed regulatory body as well as smallholder farmers.",
"keywords": [
"Potato seed system",
"quality assurance",
"regulatory framework",
"food security"
],
"content": "Introduction\n\nThe potato (Solanum tuberosum L.), often referred to as the “perfect food” or the “underground apple,” is essential for global food security and nutrition. As the third most important food crop, it is poised to become a key player in the global food security system, particularly as the yields of other cereal crops approach their limits (Devaux et al., 2021; Wijesinha-Bettoni and Mouille, 2019). The global average yield gains from adapting to climate change range between 10 and 17% according to various climate models. Compared to other major crops, potato farming produces fewer greenhouse gas emissions, making it a climate-smart choice due to the anticipated increases in yield (Jennings et al., 2020).\n\nThe potato significantly supports global food security, nutrition, and healthy diets for millions of households and for creating diversified agri-food systems (Devaux et al., 2021; Wijesinha-Bettoni and Mouille, 2019). In many developing countries, including Ethiopia, where rapid population growth, shrinking arable land, and climate change are critical challenges to food security, potatoes emerge as a strategic crop. Potatoes are particularly valuable because they yield more food per unit of land compared to other staple crops (Mijena et al., 2022; Devaux et al., 2021).\n\nEthiopia’s potato seed system faces critical challenges that impede agricultural productivity and food security (Hirpa et al., 2010). The regulatory framework governing seed production and distribution is fragmented and often ineffective, leading to a lack of clarity and consistency in seed certification processes (Getnet et al., 2023; Hirpa et al., 2010; Tessema et al., 2023a). This regulatory uncertainty discourages investment and participation from local farmers and seed producers, exacerbating the reliance on informal seed sources that compromise crop quality (Schulz et al., 2013; Katrin et al., 2023). Furthermore, quality assurance mechanisms are insufficient, resulting in the proliferation of low-quality seeds that are vulnerable to diseases and pests (Alemu et al., 2023; Nigussie et al., 2020; Tessema et al., 2023b). These issues collectively hinder the potential of the potato sector, which is vital for both the economy and nutrition in Ethiopia (Getnet et al., 2023). Addressing these challenges is essential for enhancing the resilience and sustainability of the potato seed system there by ensuring that farmers have access to high-quality seeds that can improve yields and contribute to national food security. Identifying pathways for improvement in this system is imperative to foster collaboration among stakeholders, enhance regulatory effectiveness, and ultimately support the livelihoods of millions of farmers across the country.\n\nThis topic effectively captures the multi-faceted nature of the seed system in Ethiopia, focusing on regulatory challenges, quality control, and potential improvements in the potato seed sector. Furthermore, this comprehensive review paper will provide a well-rounded review of the potato seed system in Ethiopia, highlighting both the challenges and the potential strategies for effective interventions. Therefore, this particular paper seeks to provide insights on potato seed system, regulatory challenges, quality assurance mechanisms ad leverage points for improvement pathways.\n\n\nMethods\n\nWe have conducted a literature search using different key databases to assess potato seed system, regulatory challenges, seed quality assurance bottlenecks and paths for improvement particular to potato crop in Ethiopia. These included existing reviews and reports using Web of Science, PubMed, Google Scholar, ResearchGate, the CIP database and government annual reports particular to seed system in Ethiopia. Our search employed a variety of terms, including: potato, seed system, seed quality assurance, regulatory framework, seed certification, integrated seed sector development, intervention points for seed sector development.\n\n\nOverview of potato seed system in Ethiopia\n\nThe distribution of seeds of improved varieties for farming communities started from the 1950s informally mainly with the establishment of some academic, research and development institutes in Ethiopia. Progressively, the formal seed sector began in the 1970s through several organizational and structural changes and made steady improvement across the seed system (Alemu et al., 2023). Ethiopia has a pluralistic seed system for crops like potato comprising formal, alternative and informal schemes though scholars put different views on seed system categorization (Haug et al., 2023; Mulesa et al., 2021; Hirpa et al., 2010). The contribution of informal seed system to planting stock in Ethiopia may be 98.3% with the remaining 1.3% from alternative and the formal sources contributing a very insignificant fraction (Schulz et al., 2013). Thus, almost all potato farmers in Ethiopia use own-saved seed tubers and seed from their social networks due to various reasons (Tadesse et al., 2019). As a developing country that lacks a well-functioning seed certification system, Ethiopia adopted the quality declared seed (QDS) for many economically important crops including potato (Tessema et al., 2023a). QDS, a class below certified seed is guided by standards that are less rigorous but recognized by the regulatory bodies than ordinary seed is permitted in the Ethiopian seed potato system (Schulz et al., 2013; Tessema et al., 2023a,b). The management and handling of these different seed systems are quite distinct in terms of seed quality, resource utilization, knowledge of seed operating personnel, seed quality assurance/control mechanisms and proscription by law (Hirpa et al., 2010; Gowda et al., 2017). Furthermore, the productivity of the crop from each seed system/category has considerable difference, for example in Ethiopia; a yield penalty of 35% was reported for some field crops in each hectare when farmers used informal/local seed as their planting material (Tarekegn and Mogiso, 2020). Thus, sowing/planting quality seed as a source material has considerable yield advantages (Harahagazwe et al., 2018; Gaur et al., 2020). Furthermore, The primary aim of functional seed systems is to guarantee that seeds are accessible and available to all users, especially smallholder farmers providing an adequate quantity, quality, and variety of seeds to enable sustainable food production and consumption (Etten et al., 2017). However, in Ethiopia, there is no well delineated seed system that fulfill the required role delegations along the seed value chain of many crops especially VPCs.\n\nThe decentralized seed potato system in Ethiopia involves individual farmers, seed grower cooperatives and private seed multipliers at different level of economic, social and agro-ecological settings (Tadesse et al., 2020, 2023a; Sulle et al., 2022). However, public seed enterprises are less likely to engage in the potato seed business in the country (Getnet et al., 2023) and there are no well-organized seed growers except local seed multipliers.\n\nThe potato seed system is constrained by tremendous social, economic and biological factors with limited quality assurance capacity (Tafesse et al., 2020). Most visible, the decentralized seed system has poor monitoring and administration capacity in farmers cooperatives and weak coordination among the seed regulatory authority (Sulle et al., 2022; Tadesse et al., 2020). The sub-sector is characterized by poor performance, low stakeholder collaboration, weak coordination and inefficient service provision in terms of quality seed production and certification (Getnet et al. 2023; Tessema et al., 2023b). The mechanisms of applying seed laws, operating procedures and quality standards depends on availability of infrastructure, trained human resources managing the seed system and other interrelated aspects (Misra et al., 2023). Generally, the seed system in Ethiopia is still at its infant stage to perform key functions of seed systems viz., production and distribution, innovation and regulation along the seed value chain that ultimately affects sustainable potato production and supply (Tessema et al., 2023a; Hirpa et al., 2010; Etten et al., 2017). This is because the seed sector directly influences three dimensions of food security and nutrition namely; food availability, access and affordability (Etten et al., 2017).\n\nThe seed sector in Ethiopia was coordinated by various state ministers under the Ministry of Agriculture (MoA). Linked to the federal government, the seed quality assurance is cascaded from Federal to Regional regulatory Authorities (Nigussie et al., 2020). Since 2021, the Ethiopian Agricultural Authority (EAA) under the MoA was established to coordinate all regulatory aspects of the seed sector in Ethiopia Seed Proclamation No. 1262/2021 (Alemu et al., 2023). Functionally, the seed regulatory laboratories are located at zonal level under the regional agricultural inputs regulatory authority (Figure 1). Seed regulatory laboratories work mostly on seed of cereal and grain crops and rarely on VPCs that require more advanced pathogen testing facilities and skilled human resource that are currently in short supply in the country (Tessema et al., 2023a). Seed regulatory laboratories in Ethiopia are essential for testing and certifying seed quality, yet they face significant challenges such as inadequate funding and outdated equipment with limited trained man power (Tessema et al., 2023b).\n\nThe vulnerability of potato to seed-borne diseases and pests requires a strong, efficient and customized regulatory mechanism (Getnet et al., 2023). The seed regulatory laboratories have a plethora of problems including coordination and capacity bottlenecks to undertake the potato seed quality assurance within the standards set by national or international authorities to achieve the seed sector transformation goal in Ethiopia comparable to cereals and legumes (Alemu et al., 2023; Nigussie et al., 2020).\n\nSeed quality is a complex trait that involve a combination of plant genetics, seed technology, seed health and molecular biology. It is one of the basic requirements of effective seed industry (Misra et al., 2023). Some of the classical methods of seed improvement include coating, pelleting, priming, and production of artificial seed (Wimalasekera, 2015). The seed of VPCs, unlike cereals and pulses are very prone to latent infection by seed and soil borne pathogens such as Ralstonia solanacearum and viruses (Bentley et al., 2018; Tessema et al., 2022).\n\nSeed certification is the process to ensure that the genetic identity and purity of a plant variety are maintained during seed multiplication.\n\nThe seed certification schemes rely on standards and procedures implemented at each step of the seed production process. Seeds for sale with a label of “Certified seed”, means that the seed complies with the national quality standards prescribed for certification. Under the seed law, the government seed authority is responsible for the process of seed certification where government carries out the task for seed certification (Misra et al., 2023). However, in Ethiopia the seed standards set by the national seed regulatory authority are poorly implemented by the seed laboratories (Tessema et al., 2023a; Nigussie et al., 2020) resulting in farmers planting disease-infected, low quality seed potato. The most detrimental effect of seed-borne pathogens such as potato bacterial wilt (BW) besides affecting immediate yield is the contamination of previously disease-free areas and the spread of new diseases (Tessema et al., 2023a, b; Singh and Rathaur, 2020).\n\nWithout an active seed certification program, the quality of seed tubers is upheld by staff from research organizations and seed potato projects, who work together to maintain minimum quality standards (Schulz et al., 2013: Getnet et al., 2023). However, as the demand for quality seed increases, this system is starting to hit its production limits. Additionally, its reliance on project interventions makes it unsustainable. Therefore, alternative mechanisms at regional or local levels should be developed, tested, and promoted to ensure that producers of planting materials meet minimum quality standards at smallholders setting. To withstand the seed demand, quality declared seed (QDS) is introduced to the potato seed system that uses slight quality assurance mechanisms (Tessema et al., 2023a). The QDS system somehow reduces the burden of the seed sector by allowing a 10% external seed inspection by the regulatory body, where as 90% seed quality control is left to the producers (Figure 2) (Tessema et al., 2023a). Scholars also recommend various seed regulatory options tailored to the specific circumstances of each region or country, although these recommendations are often poorly implemented (Gatto et al., 2021).\n\nRegulatory challenges related to seed of vegetatively propagated crops largely center on varietal identification, certification, and disease control. In contrast to seed-propagated crops, which have clear genetic profiles, vegetatively propagated crops often show considerable variability, making it difficult to establish distinct and consistent varieties (Gatto et al., 2021). This ambiguity creates hurdles for regulatory agencies responsible for enforcing plant breeding and protection standards (McEwan et al., 2021; Louwaars et al., 2013) (Table 1). Moreover, the certification of propagation materials like cuttings and tubers requires thorough testing to ensure they are free from diseases and pests, a process that can be complex and resource-intensive (Tessema et al., 2023a; Almekinders et al., 2019).\n\nAdditionally, the intellectual property framework for vegetatively propagated crops introduces further regulatory complications (Gatto et al., 2021). Current plant variety protection laws may not sufficiently accommodate the specific traits of these crops, potentially hindering the ability to secure patents or protection certificates. Traceability is another critical issue, as it is essential to track the origins and quality of vegetative materials throughout the supply chain to uphold biosecurity and market integrity (Zheng et al., 2023). As nations implement varying regulations for the import and export of these crops, navigating the international regulatory landscape becomes more challenging, highlighting the need for collaboration among stakeholders to establish effective and coherent regulatory systems (McEwan et al., 2021; Gatto et al., 2021).\n\nIn Ethiopia, research conducted in collaboration with the Ethiopian Institute of Agricultural Research (EIAR) and the regional Bureaus of Agriculture and Natural Resource Development revealed that six major potato viruses and bacterial wilt are prevalent throughout all levels of the seed system (Sulle e al., 2022; Tessema et al., 2023b, 2024; McEwan et al., 2023). However, an in-depth assessment of seed testing laboratories and seed inspection processes indicated limited resources and capabilities for implementing seed quality assurance.\n\nOne of the most significant challenges in potato seed systems is the infiltration of counterfeit or substandard seeds into the supply chain (Hirpa et al., 2010; Sulle et al., 2022). The lack of a robust, digitized, and automated system makes it relatively easy for these fraudulent seeds to enter the market (Tessema personal communication). This not only undermines seed quality but also leads to substantial losses for farmers who unknowingly buy and plant these counterfeit seeds (Tessema et al., 2023a; Sulle et al., 2022). Additionally, the widespread presence of such seeds compromises the integrity of the seed industry and negatively impacts overall crop production and harvest quality (Buddenhagen et al., 2017; Tessema et al., 2024). The absence of digitization and automation in the seed delivery system contributes to seeds’ need for visibility and traceability (Tessema personal communication) (Figure 2).\n\nThis lack of transparency poses risks related to quality, expiry, counterfeiting, and accountability in the seed supply chain since the seed quality is often unobservable through visual inspection by the farmers (McEwan et al., 2021).\n\nImproving seed quality assurance is vital for boosting agricultural productivity and sustainability (Wimalasekera, 2015). Seed potatoes are fundamental to both the quality and yield of potato crops, acting as the first link in the entire potato value chain (Yves and Quere, 2023). Here are some key points to consider for improving seed systems:\n\n• Working together to harmonize seed regulations and ensure better compliance through identification of intervention points for improved seed system development.\n\n• Engaging farmers, researchers, policy makers and the public in the regulatory process is imperative to build trust among value chain actors and lead to better outcomes.\n\n• Maximizing thew potential of the informal seed sector, since the majority of the seed smallholder farmers used is sourced from informal see system.\n\n• Improving public understanding of seed technologies and regulatory practices can counter misinformation and encourage acceptance.\n\n• Integrating sustainability criteria into seed regulations can promote the development of environmentally friendly practices that in turn builds the capacity of smallholder seed producers.\n\n\nConclusions\n\nEthiopia’s potato seed system faces significant regulatory challenges that hinder its development and efficiency. One of the primary issues is the lack of a coherent regulatory framework that governs seed production and distribution. Existing regulations are often outdated or poorly enforced, leading to inconsistencies in quality and availability. Furthermore, the bureaucratic processes involved in obtaining seed certification can be cumbersome and time-consuming, discouraging local farmers and seed producers from engaging in formal markets. The interplay between various regulatory bodies can create confusion, resulting in overlapping mandates and insufficient support for stakeholders at different levels. Addressing these regulatory challenges is crucial for creating a more robust potato seed system that can better meet the needs of Ethiopian farmers.\n\nTo enhance Ethiopia’s potato seed system, a multifaceted approach is necessary, focusing on strengthening regulatory frameworks, improving quality assurance, and fostering collaboration among stakeholders. First, reforming and streamlining the regulatory processes can help reduce bureaucratic bottlenecks, making it easier for seed producers to operate and access markets. Second, investing in research and development can lead to the creation of more resilient and high-yielding potato varieties that are better suited to local conditions. Engaging farmers in participatory breeding programs can also empower them to influence seed variety development. Lastly, promoting public-private partnerships can facilitate knowledge transfer and resource sharing, ultimately leading to a more integrated and effective potato seed system. By addressing these key areas, Ethiopia can significantly improve its potato seed system, benefiting farmers and enhancing food security in the country as well.\n\n\nAdditional information\n\n\n\n• Lemma Tessema conceived and designed the experiments, performed the experiments, prepared figures and/or tables, authored or reviewed drafts of the article, and approved the final draft.\n\n• Ebrahim Seid performed the experiments, authored or reviewed drafts of the article, and approved the final draft.",
"appendix": "Data availability Statement\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nWe acknowledge our institute for providing necessary facilities during this work.\n\n\nReferences\n\nAlemu D, Bishaw Z, Zeray T, et al.: National Seed Sector Coordination in Ethiopia: Status, Challenges, and Way Forward.2023. Reference Source\n\nAlmekinders CJM, Walsh S, Jacobsen KS, et al.: Why interventions in the seed systems of roots, tubers and bananas crops do not reach their full potential. Food Secur. 2019; 11: 23–42. Publisher Full Text\n\nBentley JW, Andrade-Piedra J, Demo P, et al.: Understanding root, tuber, and banana seed systems and coordination breakdown: A multi-stakeholder framework. J. Crop Improv. 2018; 32(5): 599–621. Publisher Full Text\n\nBuddenhagen CE, Hernandez Nopsa JF, Andersen KF, et al.: Epidemic Network Analysis for Mitigation of Invasive Pathogens in Seed Systems: Potato in Ecuador. Phytopathology. 2017; 107(10): 1209–1218. PubMed Abstract | Publisher Full Text\n\nDevaux A, Goffart JP, Kromann P, et al.: The Potato of the Future: Opportunities and Challenges in Sustainable Agri-food Systems. Potato Res. 2021; 64: 681–720. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEtten JV, López Noriega I, Fadda C, et al.: The contribution of seed systems to crop and tree diversity in sustainable food systems.2017. [Accessed on 15 April 2024]. Reference Source\n\nGatto M, Le PD, Pacillo G, et al.: Policy options for advancing seed systems for vegetatively propagated crops in Vietnam. J. Crop Improv. 2021; 35(6): 763–789. Publisher Full Text\n\nGaur A, Kumar A, Kiran R, et al.: Importance of Seed-Borne Diseases of Agricultural Crops: Economic Losses and Impact on Society.Kumar R, Gupta A, editors. Seed-Borne Diseases of Agricultural Crops: Detection, Diagnosis & Management. Singapore: Springer; 2020. Publisher Full Text\n\nGetnet M, Teshome A, Snel H, et al.: Potato seed system in Ethiopia: challenges, opportunities, and leverage points. Stichting Wageningen Research Ethiopia, Addis Ababa. 2023. SWRE-RAISE-FS-23-025. Publisher Full Text\n\nGowda M, Worku M, Nair SK, et al.: Quality Assurance/Quality Control (QA/QC) in Maize Breeding and Seed Production: Theory and Practice. Nairobi: CIMMYT; 2017. 978-9966-1971-9-1.\n\nHarahagazwe D, Condori B, Barreda C, et al.: How big is the potato (Solanum tuberosum L.) yield gap in Sub-Saharan Africa and why? A participatory approach. Open Agric. 2018; 3: 180–189. Publisher Full Text\n\nHassena M, Alemu D, Dey B: Seed policy provisions and operational challenges in Ethiopia. A Feed the Future Global Supporting Seed Systems for Development activity (S34D) report.2023. Reference Source\n\nHaug R, Hella JP, Mulesa TH, et al.: Seed systems development to navigate multiple expectations in Ethiopia, Malawi and Tanzania. World Dev. Sustain. 2023; 3: 100092. Publisher Full Text\n\nHirpa A, Meuwissen MPM, Tesfaye A, et al.: Analysis of Seed Potato Systems in Ethiopia. Am. J. Potato Res. 2010; 87: 537–552. Publisher Full Text\n\nJennings SA, Koehler A-K, Nicklin KJ, et al.: Global Potato Yields Increase Under Climate Change with Adaptation and CO2 Fertilisation. Front. Sustain. Food Syst. 2020; 4: 519324. Publisher Full Text\n\nKatrin A, Tara F, Indulekha T, et al.: Laws and regulations enabling and restricting Africa’s vegetable seed sector. Int. J. Agric. Sustain. 2023; 21(1): 2210005. Publisher Full Text\n\nLouwaars NP, de Boef WS , Edeme J: Integrated Seed Sector Development in Africa: A Basis for Seed Policy and Law. J. Crop Improv. 2013; 27(2): 186–214. Publisher Full Text\n\nMcEwan MA, Almekinders CJ, Andrade-Piedra JJ, et al.: “Breaking through the 40% adoption ceiling: Mind the seed system gaps.” A perspective on seed systems research for development in One CGIAR. Outlook Agric. 2021; 50(1): 5–12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcEwan MA, Kumar L, Legg J, et al.: Enhancing seed quality assurance: Options for vegetatively propagated crops. ISSD Africa Topical Synthesis Paper.2023. [Accessed on 23 April 2024]. Reference Source\n\nMijena GM, Gedebo A, Beshir HM, et al.: Ensuring food security of smallholder farmers through improving productivity and nutrition of potato. J. Agric. Food Res. 2022; 10: 100400. Publisher Full Text\n\nMisra MK, Harries A, Dadlani M: Role of Seed Certification in Quality Assurance.Dadlani M, Yadava DK, editors. Seed Science and Technology. Singapore: Springer; 2023. Publisher Full Text\n\nMulesa TH, Dalle SP, Makate C, et al.: Pluralistic seed system development: a path to seed security? Agronomy. 2021; 11(2): 372. Publisher Full Text\n\nNigussie M, Kalsa K, Ayana A, et al.: Status of Seed Quality Control and Assurance in Ethiopia: Required Measures for Improved Performance. Technical report. 2020. Publisher Full Text\n\nSchulz S, Woldegiorgis G, Hailariam G, et al.: Sustainable seed potato production in Ethiopia: from farm-saved to quality declared seed.Woldegiorgis G, Schulz S, Berihun B, editors. Proceedings of the National Workshop on Seed Potato Tuber Production and Dissemination: Experiences, Challenges and Prospects, 12-14 March 2012. Bahir Dar, Ethiopia: Ethiopian Institute of Agricultural Research and Amhara Regional Agricultural Research Institute; 2013; pp. 60–80. Reference Source\n\nSingh D, Rathaur PS: Detection of Seed and Propagating Material-Borne Bacterial Diseases of Economically Important Crops.Kumar R, Gupta A, editors. Seed-Borne Diseases of Agricultural Crops: Detection, Diagnosis & Management. Singapore: Springer; 2020. Publisher Full Text\n\nSulle E, Pointer R, Kumar L, et al.: Inventory of novel approaches to seed quality assurance mechanisms for vegetatively propagated crops (VPCs) in seven African countries. International Institute of Tropical Agricultu re (IITA). International Potato Center (CIP); 2022; 48. Publisher Full Text\n\nTadesse Y, Almekinders CJM, Griffin D, et al.: Collective Production and Marketing of Quality Potato Seed: Experiences from Two Cooperatives in Chencha, Ethiopia. Forum Dev. Stud. 2020; 47(1): 139–156. Publisher Full Text\n\nTadesse Y, Almekinders CJM, Schulte RPO, et al.: Potatoes and livelihoods in Chencha, southern Ethiopia. NJAS Wageningen J. Life Sci. 2019; 88: 105–111. Publisher Full Text\n\nTafesse S, Lie R, van Mierlo B , et al.: Analysis of a monitoring system for bacterial wilt management by seed potato cooperatives in Ethiopia: Challenges and future direction. Sustainability. 2020; 12: 3580. Publisher Full Text\n\nTarekegn K, Mogiso M: Assessment of improved crop seed utilization status in selected districts of Southwestern Ethiopia. Cogent Food & Agriculture. 2020; 6(1): 1816252. Publisher Full Text\n\nTessema L, Kakuhenzire R, McEwan M: Latent bacterial wilt and viral infection burden in the seed potato system in Ethiopia: Policy implications for seed potato. Policy Brief 02. International Potato Center; 2023b. Reference Source\n\nTessema L, Kakuhenzire R, Seid E, et al.: Detection of six potato viruses using double antibody sandwich ELISA from in vitro, screen house and field grown potato crops in Ethiopia. Discov. Appl. Sci. 2024; 6: 79. Publisher Full Text\n\nTessema L, Negash W, Kakuhenzire R, et al.: Seed health trade-offs in adopting quality declared seed in potato farming systems. Crop Sci. 2023a; 64(3): 1340–1348. Publisher Full Text\n\nTessema L, Seid E, W/Giorgis G, et al.: Incidence and occurrence of latent Ralstonia solanacearum infection in seed potato from farmer seed grower cooperatives in Southern and Central Ethiopia. Potato Res. 2022; 65: 649–662. Publisher Full Text\n\nWijesinha-Bettoni R, Mouille B: The Contribution of Potatoes to Global Food Security, Nutrition and Healthy Diets. Am. J. Potato Res. 2019; 96: 139–149. Publisher Full Text\n\nWimalasekera R: Role of Seed Quality in Improving Crop Yields.Hakeem K, editor. Crop Production and Global Environmental Issues. Cham: Springer; 2015. Publisher Full Text\n\nYves LH, Quere B: Seed potato production, certification, and trade.Caliskan ME, Bakhsh A, Jabran K, editors. Potato Production Worldwide. Academic Press; 2023; pp. 241–260. Publisher Full Text\n\nZheng Y, Xu Y, Qiu Z: Blockchain Traceability Adoption in Agricultural Supply Chain Coordination: An Evolutionary Game Analysis. Agriculture. 2023; 13: 184. Publisher Full Text"
}
|
[
{
"id": "340501",
"date": "15 Jan 2025",
"name": "Kwame Ogero",
"expertise": [
"Reviewer Expertise Seed systems",
"pest and disease management"
],
"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 review gives a good summary of the bottlenecks facing the potato seed systems in Ethiopia. The regulatory issues and quality assurace practices are well captured and a clear way forward presented. I recommend the article for indexing after an editorial review to correct typos and structure of some sentences.\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": "357063",
"date": "30 Jan 2025",
"name": "Femi Emmanuel Awosanmi",
"expertise": [
"Reviewer Expertise Seed Science and 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\nThe Review article gave insight into the Ethiopian Seed System and highlighted the challenges facing the sector and the consequences of these on the Potato production industry in particular. The authors also made good, significant suggestions to tackle these challenges to establish a viable potato seed production system that would enhance the yield and productivity of potato in Ethiopia.\n\nHowever, it will be appropriate for the authors to maintain a definite pattern of citing references throughout the article; provide the full meaning of VPC where it was mentioned; give an explanation on COC licences because of audience who are not based or familiar with Ethiopia; and reflect the National Seed Regulatory authority mentioned on the Organizational diagram as mentioned in the text.\n\nAlso, the conclusion that \"The interplay between various regulatory bodies can create confusion, resulting in overlapping mandates and insufficient support for stakeholders at different levels\" was not clearly reflected in the main text.\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1348
|
https://f1000research.com/articles/13-809/v1
|
17 Jul 24
|
{
"type": "Research Article",
"title": "Selfies, narcissism and oral health a cross - sectional study among adolescents and young adults in Mangaluru - India.",
"authors": [
"Preeti Prabhu",
"Mithun Pai",
"Shweta Yellapurkar",
"Srikant Natarajan",
"Amit Vasant Mahuli",
"Preeti Prabhu",
"Shweta Yellapurkar",
"Srikant Natarajan",
"Amit Vasant Mahuli"
],
"abstract": "Background Selfies have been defined as “a photograph that one has taken of oneself, and are a continuing growing trend among Millennials. Narcissism refers to the personality trait of an extraordinary self-awareness and adoration. Studies have shown a close relationship between selfie-taking behaviour, narcissism and oral health. Hence, a study was conducted with aim of the influence of selfie-taking behavior and narcissism on oral health.\n\nMethods An analytical cross-sectional questionnaire study was designed using relevant literature for collating information on sociodemographic characteristics, frequency of dental visits, selfie-taking behavior and perceived oral health. Oral health examination was performed to assess decay and plaque. Narcissism was assessed using The Five-Factor Narcissism Inventory Short Form\n\nResults The study included a sample of 163 participants. The associations between selfies taken per day and perceived oral health was statistically significant (p value 0.047*). Binary logistic regression models were constructed, which were significant for perceived oral health and grandiose fantasy. Plaque Scores showed significant corelations between indifference, manipulativeness, thrill seeking and age. Step forward binary regression demonstrated a significant odds ratio for grandiose narcissism followed by selfie-taking behavior\n\nConclusion This study revealed a correlation between perceived oral health and selfie-taking behaviour. Further studies are required to assess selfie-taking behaviour and oral health.",
"keywords": [
"Adolescents",
"Narcissism",
"Oral health",
"perceived health",
"selfie."
],
"content": "Background\n\nSelfies have been defined as “a photograph that one has taken of oneself, typically one taken with a smartphone or webcam and shared via social media” and are a continuing growing trend among Millennials (Generation Y).1 Selfies are now correlated with uploading the same on social media platforms, mainly because of the global saturation of smartphones with cameras and the indispensable integration of this with the presence of Social networking sites (SNS), applications such as Facebook, Twitter, WeChat, Tumblr, Snapchat and Instagram. Selfies, as a new social trend, warrant greater academic consideration, and the intention behind selfie taking is still an enigma in the field of psychology, which warrants further exploration of the intent behind this behavior. Not much is known about selfie addiction in general, and selfies, in particular, have come under increased scrutiny because of their disbursing nature, and experts in the field of psychology and communication are trying to investigate this phenomenon in detail.2 Over the past few years, the triple digital revolution of social networks, the internet, and mobile phones has increased the use and popularity of selfies.\n\nNarcissism refers to the personality trait of an extraordinary self-awareness and adoration often referred as “self-love that shut out everyone else”.3 The word “narcissism” is typically associated with increased self-worth, feelings of grandiosity, dominance, admiration seeking, and privilege (entitlement), which forms a part of narcissism called the grandiose narcissism, but there also is a less prominent trait called Vulnerable narcissism which includes self-absorption, self-consciousness, social insecurity, and defensiveness. Together they revolve on the fundamental idea of self-centered egocentric behavior; they initially appeared as the “two faces” of narcissism and show up as radically distinct personality traits.4\n\nPersonality and its developmental aspects among individuals are extending the frontiers in psychology. Studies have shown efficient integration between the Big Five personality traits and various dimensions of SNSs, such as communication patterns and social media language, along with a wealth of vocabulary.5 Additionally, there is a direct association between the Dark Triad and personality traits, as mentioned earlier. Additionally, psychological traits could also be related to selfie posting behavior. Therefore, selfies are no longer considered merely technological artifacts. Instead, it is considered a means of communication and a purposeful symbolic gesture.6\n\nPerceived oral health depends on factors such as well-being, self-satisfaction and, most importantly, oral health habits such as the frequency of tooth brushing, flossing and dental visits. A study conducted on the influence of narcissism on oral health status showed that good/excellent self-rated oral health status was associated with high levels of narcissism.7\n\nThe study was envisaged with the aim and objective of assessing correlations between perceived health, perceived oral health, selfie-taking behavior, narcissism and oral health status using a standard questionnaire among a population of college students in Mangaluru, Karnataka.\n\n\nMethods\n\nThis Analytical Cross-sectional study was carried out in the city of Mangaluru, located on the west coast of Karnataka, India in the district of Dakshina Kannada. It is the educational centre in the state of Karnataka. The study was conducted from 2019-2021 as part of an oral health screening programme at the college as part of the institutional health screening programme. The students from the Department of Business Studies were the participants in the study. A Convenient sample was obtained and all students from the department who were eligible for study were included in the study.\n\nEligibility criteria: Individuals who declined to give their consent were excluded from the study. The study comprised participants who were present during the study process and could communicate in English as the questionnaire was in English only.\n\nParticipants who were receiving psychiatric therapy or who were suffering from generalised anxiety disorders, who mentioned it in the questionnaire were excluded from the study.\n\nEthics: The approval was obtained from the Institutional Ethics Committee. [Protocol No: 18018]. Permission was obtained from the head of the institution of the college. Participants provided written informed consent before answering the questionnaire and undergoing an oral examination. Participants in need of urgent oral care were referred to the institution for oral emergency care.\n\nThe Statistical Package for Social Sciences (SPSS), version 16.0 (SPSS Inc., Chicago IL), was used to analyze the data. We computed the mean and standard deviation for describing the data. The relationships between the five-factor narcissism subscale domain scores and the practice of taking selfies were examined using independent t tests. The chi-square test and Fisher’s exact test were used for comparisons of selfie-taking behaviour and perceived oral health, perceived general health, DMFT score and the plaque index. Pearson product-moment correlation was used to assess the correlation between selfie-taking behavior and different traits of narcissism, namely, grandiose and vulnerable narcissism, antagonism, extraversion, and neuroticism. Binary logistic regression was used to predict perceived oral health using narcissism, selfie behavior and gender.\n\nThe questionnaire included demographic information (age, sex, education, family monthly income, previous dental visits and medical history), selfie-taking behaviour, perceived oral health and questions on perceived general health with closed-ended responses. Narcissism was assessed using a short questionnaire version of The Five-Factor Narcissism Inventory Short Form (FFNI-SF). Glover et al. (2012) created the Original Five-Factor Narcissism Inventory (FFNI), a 148-item self-report tool with 15 features meant to evaluate the essential factors of narcissism.8 The FFNI assesses both variants of namely vulnerable and grandiose narcissism. The Five-Factor Narcissism Inventory Short Form (FFNI-SF) was conceived by Sherman et al., 2015, as the original FFNI was extensive and not practical for overall use. The sixty-item FFNI-SF assesses three higher-order qualities (neuroticism, extraversion, and antagonism) as well as fifteen traits that can be combined to evaluate grandiose and vulnerable narcissism. It was also established that the constituents of the FFNI-SF can be valid and reliable.9–11\n\n\nResults\n\nThe study included a sample of 163 participants, 159 of whom completed the study, with a response rate of 97%, 96 of whom were males and 63 of whom were females. The sample had a mean age of 18.03 years, with a 4.3-year standard deviation, 71.1% had visited a dentist before this study was conducted.\n\nThe Pearson chi-square test was used to assess the associations between selfie-taking behaviour, perceived general health, perceived oral health, dental caries experience, and the plaque index. The associations between selfies taken per day and perceived oral health was statistically significant (p value 0.047*), but there was no association with other variables, as described in Table 1.\n\nThe Pearson correlation coefficients between total narcissism, grandiose narcissism, vulnerable narcissism, dental caries, perceived oral health, and the plaque index showed a statistically significant positive correlation between perceived oral health and vulnerable narcissism and total narcissism, but there was no statistically significant correlation between grandiose narcissism or dental caries experience and plaque scores. However, a significant negative correlation was observed between grandiose narcissism and the plaque index. The correlations between all the covariables are detailed in Table 2. Further evaluation between selfie behaviour and covariables revealed a positive significant correlation between gender and selfie behaviour.\n\nIndependent t tests were used to assess differences between selfie-taking behavior and differing traits of narcissism. The test demonstrated no significant association between the various traits of narcissism and selfie behavior, as presented in Table 3.\n\nBinary logistic regression models were constructed for the prediction of perceived oral health, DMFT index, presence or absence of caries and plaque, traits of narcissism, gender, and selfie-taking behaviour. The odds were significant for perceived oral health and grandiose fantasy. Plaque Scores showed significant corelations between indifference, manipulativeness, thrill seeking and age. Multiple charts for binary logistic regressions are collated with only odds ratios, and unstandardised regression rates for better understanding and presented in Table 4.21\n\nTables 5 and 6 show the results of forward stepwise binary logistic regression for the prediction of poor perceived oral health and plaque indices using the traits of narcissism, gender, and selfie behaviour. The step forward binary regression demonstrated a significant odds ratio for grandiose narcissism followed by selfie-taking behavior as the key variable associated with plaque behaviour.\n\n\nDiscussion\n\nAdolescence is described as a transitional phase between childhood and adulthood, with a biological beginning (puberty) and a social ending. Adolescents are a susceptible group; they are the connect between young and old and are often the population that is routinely under scrutiny because of their diverse physical and psychological traits. Adolescence is a period of profound physical, psychological, and behavioral transformation during which adolescents form habits and behaviors that they carry into adulthood. In addition, there are more specific risk factors linked to poor dental health at the period. Adolescents constitute a major part of the population, yet there are still limited studies regarding the population, especially in dental settings.12\n\nThe main objectives of the study were to evaluate the associations between perceived health, perceived oral health, selfie-taking behavior, narcissism and oral health status in an adolescent population in a coastal city in Karnataka, India. Multiple studies have assessed the association between selfie-taking behaviour and narcissism,12,13 and studies have also demonstrated the effect of narcissistic personality disorders on oral health.4,7,14\n\nThe instrument used for this study was a validated version of the short Form of Five-Factor Narcissism Inventory with the following characteristics: a Cronbach’s alpha of 0.8, a split half of 0.8 and a test-retest reliability of 0.71 (p<0.01), as tested by the authors on a population similar to that used in the study. The Five-Factor Narcissism Inventory Short Form (FFNI-SF) was created because the original Five-Factor Narcissism Inventory (FFNI) was too lengthy and unworkable for general usage. The 60-item FFNI-SF assesses the three higher order elements of narcissism anger, extraversion, and neuroticism as well as the same 15 characteristics that can be combined to produce grandiose and vulnerable narcissistic presentations. Sherman et al.9 reported that the sixty items of the FFNI-SF may still be used to measure the original FFNI’s constituents in a valid and reliable manner, boosting the instrument’s efficiency while maintaining its validity and reliability.11 Narcissism has been explored in terms of subtypes rather than as a singular construct. Grandiose (the overt kind) and vulnerable (the covert type) are two of the most discussed forms of pathological narcissism.10\n\nThe associations between selfie taking behaviour and perceived general health, perceived oral health, dental experience and plaque scores were significant only between selfie behaviour and perceived oral health. There have been nearly no studies in the literature that have examined selfie behaviour in terms of perceived health, perceived oral health and dental status in a population, which is understandable because selfies and oral health were considered unrelated phenomena or because no close associations are observed between them; however, recently, the upsurge in social media and its close association with selfie behaviour have led investigators to scrutinise this phenomenon on the whole. Studies in South Africa15,16 have pointed out that dental health, especially perceived dental health, is closely related to selfie behaviour, as people with malocclusion are averted from smiling in selfies; hence, this may explain the association between these two factors. Adolescents lead a carefree life with less importance to health, a healthy lifestyle and well-being; hence, they usually have positive perceptions of health as generally being positive regardless of what they might be going through; hence, there might be no association with perceived health and other factors.\n\nA positive correlation was observed between total narcissism, vulnerable narcissism and perceived oral health. Research has shown that there are two main narcissistic variants, namely, grandiose and vulnerable narcissism. The primary difference between the two variants is self-regulation. Grandiose narcissists typically use overt techniques to control their ego, such as discounting others and enhancing their own worth, whereas vulnerable narcissists typically depend on social acceptance to control their delicate ego. Vulnerable types are more likely to recognise and counteract challenges to their self-image. Hence, there may be a positive correlation between perceived oral health and vulnerable narcissism, and people with high levels of vulnerable narcissism may experience dissatisfaction from their narcissistic demands for approval and achievement.17\n\nThey are also more self-vigilant and conscious about self-presentation. Hence, oral health, especially the aesthetic part of the face, is important for these subtypes, which can also be a reason for such correlation.18\n\nNarcissism has a close relationship with oral health parameters. The present study revealed a positive correlation between grandiose fantasy and perceived oral health. Participants with grandiose fantasy19 have closely studied the effects of grandiose fantasy on personality traits and believe that people with grandiose fantasy tend to feel better for themselves. It is also proposed that grandiose fantasising is highly prevalent in both traits of narcissism, hence the reason for a better perception of oral health.20 The traits such as indifference, manipulativeness and thrill seeking was positively related to the plaque index, where higher plaque index scores were observed in subjects with indifference, manipulativeness and thrill seeking. Compared with individuals with other personalities, individuals with narcissistic personalities who are exploring oral health behaviors are less likely to visit dentists for check-ups or for tooth cleaning and scaling.7\n\nEgocentricity, grandiosity, arrogance, entitlement, envy, impulsivity, hypersensitivity to criticism, and a lack of empathy are among the most complex personality traits recognised as narcissism. The interpersonal styles of narcissists include hostile, aggressive, insensitive, competitive, domineering, and manipulative. Conversely, the delicate and susceptible nature of narcissism makes individuals susceptible to perceived threats that stimulate feelings of rage, hatred, animosity, disdain, and humiliation. According to theoretical and empirical research, narcissistic traits such as grandiosity and dominance have a protective role in regulating negative emotions and enhancing self-worth; these components render narcissism and narcissistic personality traits very difficult to understand and comprehend.\n\nThe present study has limitations that merit attention. First, as noted above, we are attempting to predict behaviours at a relatively young age the possible relations might need to be explored later in development and might change during further course of life. Future research should investigate these developmental links later in young adulthood when these behaviours become more common. Furthermore, our study design does not allow any causative explanations. The study was done in a single setting and had more male participants, this might affect the overall outcome variables as multiple studies have pointed out the effect of selfie and narcissism to be corelated to females than males.\n\n\nConclusion\n\nThis research establishes a significant correlation between the act of taking selfies and several psychological and social factors. Since adolescents and young adults make up a significant portion of the population and, if ignored, could eventually pose a major threat to public health, the correlations and association of these parameters with the various stages of development in the adolescent population serve as a foundation for additional research. This study revealed a correlation between perceived oral health and selfie-taking behaviour. However, no associations were found between selfie-taking behavior, narcissism, perceived oral health, mean DMFT score and mean plaque score. Further studies are required to assess selfie taking behaviour and oral health.\n\nEthical clearance was obtained from the Institutional Ethics Committee of Manipal College of dental Sciences. Mangaluru [Protocol No: 18018 dated 10/03/18]. Informed Consent: Informed consent was obtained from all individual participants included in the study. Written informed consent was obtained from the study participants prior to the distribution of questionnaire.",
"appendix": "Data availability\n\nFigshare: Selfies, Narcissism and Oral health a cross - sectional study among Adolescents and young adults in Mangaluru - India. https://doi.org/10.6084/m9.figshare.26143195.v4 21\n\nThis project contains the following underlying data:\n\n• Dr Mithun Narrsisism and oral health.xlsx (Raw data from questionnaire responses)\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nFigshare: Selfies, Narcissism and Oral health a cross - sectional study among Adolescents and young adults in Mangaluru - India. https://doi.org/10.6084/m9.figshare.26143195.v4 21\n\nThis project contains the following underlying data:\n\n• Table 4: Binary logistic regression for Prediction of perceived oral health using narcissism, selfie behaviour and gender\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nFigshare: STROBE checklist for Selfies, Narcissism and Oral health a cross - sectional study among Adolescents and young adults in Mangaluru - India. https://doi.org/10.6084/m9.figshare.26143195.v4 21\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\nSarose S, Banseria R, Dixit S, et al.: Assessment of selfie syndrome among the professional students of a cosmopolitan city of central India: A cross-sectional study. J. Prev. Public Health Sci. 2016; 2(2): 1–4.\n\nWickel TM: Narcissism and Social Networking Sites: The Act of Taking Selfies. Elon J. Undergrad. Res. Commun. 2015; 6(1): 5–12.\n\nFox J, Rooney MC: The Dark Triad and trait self-objectification as predictors of men’s use and self-presentation behaviors on social networking sites. Pers. Individ. Dif. 2015; 76: 161–165. Publisher Full Text\n\nParamboukis O, Skues J, Wise L: An Exploratory Study of the Relationships between Narcissism, Self-Esteem and Instagram Use. Soc Netw. 2016; 05(02): 82–92. Publisher Full Text\n\nMcCrae RR, John OP: An introduction to the five factor model and its applications.1992; 60: 175–215.\n\nMusil B, Preglej A, Ropert T, et al.: What is seen is who you are: Are cues in selfie pictures related to personality characteristics? Front. Psychol. 2017; 8(JAN). Publisher Full Text\n\nDumitrescu AL, Zetu L, Zetu M, et al.: The Relationship between Narcissism, Oral Health Status and Oral Health-related Behaviors. Procedia. Soc. Behav. Sci. 2013; 78: 496–500. Publisher Full Text\n\nGlover N, Miller JD, Lynam DR, et al.: The five-factor narcissism inventory: A five-factor measure of narcissistic personality traits. J. Pers. Assess. 2012; 94(5): 500–512. PubMed Abstract | Publisher Full Text\n\nSherman ED, Miller JD, Few LR, et al.: Development of a Short Form of the Five-Factor Narcissism Inventory: the FFNI-SF. Psychol. Assess. 2015; 27(3): 1110–1116. PubMed Abstract | Publisher Full Text\n\nEkşi F, Eksi F: The Short Form of the Five-Factor Narcissism Inventory: Psychometric Equivalence of the Turkish Version. Educ. Sci. Theory Pract. 2016 Aug [cited 2024 Jun 17]; 16(4): 1081–1096. Publisher Full Text\n\nPacker West M, Miller JD, Weiss B, et al.: Development and validation of the super-short form of the Five-Factor Narcissism Inventory (FFNI-SSF). Pers. Individ. Dif. 2021 Jul 1; 177: 110825. Publisher Full Text\n\nTsai C, Raphael S, Agnew C, et al.: Health promotion interventions to improve oral health of adolescents: A systematic review and meta-analysis. Community Dent. Oral Epidemiol. 2020 Dec 1; 48(6): 549–560. PubMed Abstract | Publisher Full Text\n\nIqbal Malik N, Umar S, Munir Dad A, et al.: Narcissism As A Predictor Of Selfie Posting Behavior And Loneliness Among University Students: Moderating Role Of Perceived Social Support.2024; 21(S8): 1159–1167. Reference Source\n\nKelleher M, Newton JT: Narcissism, pride, envy, lust and dentistry. Dent. Update. 2023 Dec 2; 50(11): 914–922. Publisher Full Text\n\nManyukwi V, Davidson CL, Van Staden PJ, et al.: Will “selfies” solve the identification crisis in lower socio-economic South Africans? A dental feature analysis of “selfies.”. S. Afr. Dent. J. 2022 Mar 8;77(01): 23–28. Publisher Full Text\n\nGuo M, De LR, Ding Y, et al.: How are extraversion, exhibitionism, and gender associated with posting selfies on WeChat friends’ circle in Chinese teenagers? Pers. Individ. Dif. 2018 Jun 1; 127: 114–116. Publisher Full Text\n\nLoeffler LAK, Huebben AK, Radke S, et al.: The Association Between Vulnerable/Grandiose Narcissism and Emotion Regulation. Front. Psychol. 2020 Oct 15; 11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKealy D, Sandhu S, Ogrodniczuk JS: Looking ahead through a fragile lens: Vulnerable narcissism and the future self.2017. Publisher Full Text\n\nFinch EF, Hooley JM: Functional fantasies: the regulatory role of grandiose fantasizing in pathological narcissism. Front. Psych. 2023; 14: 14. Publisher Full Text\n\nGuo M, De LR, Ding Y, et al.: How are extraversion, exhibitionism, and gender associated with posting selfies on WeChat friends’ circle in Chinese teenagers? Pers. Individ. Dif. 2018 Jun 1; 127: 114–116. Publisher Full Text\n\nPai M: Selfies, Narcissism and Oral health a cross - sectional study among Adolescents and young adults in Mangaluru - India. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "304575",
"date": "25 Jul 2024",
"name": "Venkitachalam Ramanarayanan",
"expertise": [
"Reviewer Expertise Dental Public Health",
"Dental Education",
"Knowledge synthesis"
],
"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: There is a disconnect between the paragraphs discussing about selfies/narcissism and perceived oral health. The rationale behind correlating the ideas of selfies, narcissism and oral health need to be elaborated further.\n\nMethods: \"It is the educational centre in the state of Karnataka\" - This statement can be removed as it is a general colloquial expression of the region.\n\nConvenience was at the level of choosing the study population or sample? If all students were included from the target population, then you could categorize this as a census survey.\n\nIt would be worthy to add a note on why Department of Business Studies was chosen as the target population.\n\nHow was the questionnaire administered? Was it self-administered or investigator administered.\nSince narcissism is also linked to anxiety, what was the rationale of excluding them? They could have been retained and adjusted for in the analysis stage. Need an explanation for the exclusion.\nPlacing data collection procedure section before statistical analysis section could ensure flow of ideas, especially with regard to the questionnaire used.\n\nResults: \"96 of whom were males and 63 of whom were females\" - I would recommend the used of percentages.\n\n\"The questionnaire included demographic information (age, sex, education, family monthly income, previous dental visits and medical history)\" - The result section does not describe information on education, family monthly income and previous dental and medical history.\n\nHow was selfie behaviour present or absent defined ? Is there an accepted measure for this ? Information regarding this aspect could be added to the methodology section.\n\nIt is not clear how information on perceived oral and general health was collected? Was it a single question or multiple questions. I'm afraid that a self perceived general health questions would be a very vague concept. Kindly attach the questionnaire used for reference. The data file uploaded as a supplementary material does not contain expansion of the questions.\n\nThe types of narcissism - grandiose, vulnerable and total could be explained in detail in introduction or results section for a reader uninitiated in this concept.\n\n'showed a statistically significant positive correlation' - what is observed based on the r values is a very weak positive correlation. R values needs to be interpreted based on its strength rather than direction and significance alone.\n\nTable 3 - need to understand the definition of selfie taking behaviour to understand the table better. Mean value is of ??\nBinary logistic regression - how were the variables selected for the model. Is age a major factor as the population is more or less of same age category (young adults and adolescents)\nDiscussion\n\nSome information from first para of discussion on adolescents could be moved to introduction to give a context to study population.\n\n'coastal' city - coastal word not relevant to the current context.\n\nnearly no studies - \"limited studies' could be a better terminology.\n\nWas the self perceived oral health question focused on perceived esthetics?\n\n\"Participants with grandiose fantasy19 have closely studied the effects of grandiose fantasy on personality traits and believe that people with grandiose fantasy tend to feel better for themselves.\" - why was this not observed with perceived general health? Any probable reason?\n\"Egocentricity, grandiosity, arrogance, entitlement, envy ............................. \" This paragraph is not linked to any of the study outcomes and seems out of place. Consider reframing it to suit the study objectives.\n\nConclusion\nThe first part of conclusion could focus on the primary objective results.\n\n\"This study revealed a correlation between perceived oral health and selfie-taking behaviour.\" - What type of correlation -- weak/strong positive/negative? Otherwise this statement is incomplete.\n\nOVERALL COMMENTS\nFor the very reason that the study delves into unexplored areas, a strong and logical reasoning is warranted to link selfies with oral health. Inclusion of few variables like DMFT, SES etc does not seem to be connected to the objective. Further explanation regarding certain aspects is missing especially selfie behaviour definition. Certain statements also lack clarity and scientific language. Interpretation of certain results like correlation and regression needs to 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? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12085",
"date": "26 Sep 2024",
"name": "Mithun Pai",
"role": "Author Response",
"response": "Respected Sir We Thank you for the comments we have incorporated the necessary editions to the manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/13-809
|
https://f1000research.com/articles/13-1346/v1
|
11 Nov 24
|
{
"type": "Method Article",
"title": "A Bioconductor/R Workflow for the Detection and Visualization of Differential Chromatin Loops",
"authors": [
"JP Flores",
"Eric Davis",
"Nicole Kramer",
"Michael I Love",
"Douglas H Phanstiel",
"JP Flores",
"Eric Davis",
"Nicole Kramer",
"Michael I Love"
],
"abstract": "Background Chromatin loops play a critical role in gene regulation by connecting regulatory loci and gene promoters. The identification of changes in chromatin looping between cell types or biological conditions is an important task for understanding gene regulation; however, the manipulation, statistical analysis, and visualization of data sets describing 3D chromatin structure is challenging due to the large and complex nature of the relevant data sets.\n\nMethods Here, we describe a workflow for identifying and visualizing differential chromatin loops from Hi-C data from two biological conditions using the ‘mariner’, ‘DESeq2’ and ‘plotgardener’ Bioconductor/R packages. The workflow assumes that Hi-C data has been processed into ‘.hic’ or ‘.cool’ files and that loops have been identified using an existing loop-calling algorithm.\n\nResults First, the ‘mariner’ package is used to merge redundant loop calls and extract interaction frequency counts. Next, ‘DESeq2’ is used to identify loops that exhibit differential contact frequencies between conditions. Finally, ‘plotgardener’ is used to visualize differential loops.\n\nConclusion Chromatin interaction data is an important modality for understanding the mechanisms of transcriptional regulation. The workflow presented here outlines the use of ‘mariner’ as a tool to manipulate, extract, and aggregate chromatin interaction data, ‘DESeq2’ to perform differential analysis of these data across conditions, samples, and replicates, and ‘plotgardener’ to explore and visualize the results.",
"keywords": [
"Hi-C",
"differential analysis",
"data visualization",
"3D chromatin structure"
],
"content": "Introduction\n\n3D chromatin structure plays a critical role in gene regulation, cellular differentiation, and response to external stimuli.1–3 Specifically, chromatin loops connect regulatory loci, such as enhancers, to gene promoters tuning levels of transcriptional.4,5 Understanding how these loops change across cell types and conditions is vital for a mechanistic understanding of transcriptional control in mammalian cells and can inform our understanding of human disease.6–9 The most comprehensive views of 3D chromatin structure are provided by Hi-C10,11 and Micro-C12 data sets; however the large and complex nature of these data sets make them challenging to manipulate and analyze. Here, we describe a Bioconductor13 workflow for the detection and visualization of differential loops from Hi-C data.\n\nWe apply this workflow to identify loops formed by an oncogenic fusion protein that is associated with acute myeloid leukemia (AML) and related hematopoietic malignancies. Most loops identified to date are driven by CTCF and cohesin proteins, which work harmoniously via loop extrusion.14,15 However, we have recently shown that an oncogenic fusion protein, NUP98-HOXA9 (NHA9), forms loops via phase separation independently of canonical loop extrusion machinery and helps drive oncogenic transcription.6 Using data from that manuscript, we describe a workflow for identifying loops formed by NHA9. Specifically, we compare loops from HEK293 cells that express either wild-type NHA9 (NHA9-WT) or a phase-separation-incompetent NHA9 mutant (NHA9-MT). The assumption is that the majority of loops in both cell types are driven by CTCF/cohesin and will not change between conditions; however, loops specific to the NHA9-WT expressing cells are driven by the phase separation capabilities of NHA9.\n\nThis workflow is based largely on three packages distributed as part of the R/Bioconductor initiative. R/Bioconductor is an open-source project that houses tools for the analysis of high-throughput biological data and provides an environment for these tools to be used in-concert. This workflow uses the ‘mariner’,16 ‘DESeq2’17 and ‘plotgardener’18 packages and can be completed entirely within the R programming environment. The ‘mariner’ package allows users to manipulate, extract, and aggregate chromatin interaction data quickly and efficiently. ‘DESeq2’ provides statistical methods to detect biological differences in read counts observed in high-throughput sequencing experiments, with applications to RNA-seq, ChIP-seq, ATAC-seq, and Hi-C count matrices. ‘plotgardener’ is a genomic data visualization package for R that allows users to programmatically and flexibly generate publication-quality multi-panel figures incorporating both genomic and non-genomic data. We recommend using the RStudio19 environment to perform these analyses because it provides an interface for smoother and more efficient coding practices, but any suitable development platform would work. The procedure described here can be applied to any comparison of Hi-C or Micro-C data from two or more cell types or conditions and provide robust detection of differential loops.\n\n\nMethods\n\nThis workflow can be applied to a variety of differential looping experiments but has several requirements and assumptions. First, the workflow requires that at least two replicates were generated in order to estimate variability and enable accurate statistical inferences. Second, it requires that the raw reads (typically ‘.fastq’ format) have been processed into Hi-C contact matrices that are stored in either ‘.hic’, ‘.cool’, or ‘.mcool’ format. This is a computationally expensive process that typically requires a computational cluster and is performed outside of the R/Bioconductor environment. Several pipelines are available to perform this initial processing step.20–23 Third, this workflow assumes that the pixels representing loops have been identified. Again, this is typically performed outside the R/Bioconductor environment and can be achieved via multiple existing algorithms.20,24–43 Finally, because we are using ‘DESeq2’ and must identify scaling factors, this workflow assumes that the majority of loops are not changing between conditions.\n\nDetailed instructions for installation of the packages used in this workflow can be found on the R/Bioconductor website but code to install the main packages used in this workflow is shown below.\n\nA list of all the packages loaded in this workflow is included at the end, in the Session information section.16–18,44–48 Once installed, the packages are loaded with the ‘library()’ function.\n\n\nUse cases\n\nThe ‘.hic’ files used in this workflow were generated by Ahn et al.6 and are available via GEO with accession number GSE143465. These experiments include four replicate Hi-C experiments for each of the two conditions. The raw reads were processed into 8 ‘.hic’ files using the Juicer pipeline.20 The .hic files can be downloaded using the following code (note-these are large files that take a substantial length of time to download).\n\nThe loops for this workflow were identified using the Significant Interaction Peak (SIP)24 and stored in a ‘BEDPE’ file format. The loop calls were generated by first merging all four ‘.hic’ files for each condition and then running SIP on the two resulting ‘.hic’ files. We find that typically we get more accurate loop calls after merging replicates, but it is also acceptable to call loops on each of the 8 ‘.hic’ files individually. The loop calls are available via the ‘marinerData’ package and can be loaded with the following code.\n\nThese loop coordinates must be modified in three ways for compatibility with the rest of the workflow. First, they must be converted from ‘BEDPE’ formatted ‘.txt’ files into ‘GInteractions’ objects in R, which we can do using the ‘as_ginteractions()’ function. Second, decreasing the resolution from 5kb to 10kb leads to increased power to detect differential loops due to an increase in the counts per pixel. For this reason, we expand the resolution of our loops from 5kb to 10kb with the ‘snapToBins()’ function.\n\n\n\n\n\n\n\nThird, because the ‘.hic’ files were assembled using a human ENSEMBL genome build that lacks the “chr” prefix to chromosomes, we also remove the “chr” prefix from the merged loops using the ‘seqlevelsStyle’ function and set it to ‘“ENSEMBL”’.\n\nThe resulting object contain ‘GInteractions’ data as well as several columns of metadata as shown below:\n\n\n\nSince loops were called in each condition separately, the union of these two sets will include many redundant loops. Moreover, due to the imprecise nature of loop calling, some of these shared loops will be assigned to slightly different, but nearby, pixels in each data set. Testing these redundant loop calls can lead to overcounting of differential loops as well as decreased statistical power due to multiple hypothesis testing correction. To address this issue, the ‘mariner’ package can remove redundant loops and create a set of consensus loop calls by clustering and merging loops between conditions using the ‘mergePairs()’ function. This ‘mergePairs()’ function uses ‘dbscan’ to cluster loops according to a user-defined ‘radius’ that specifies the maximum distance between two pixels for them to be considered as part of the same cluster. The user can specify the exact distance as well as the method of calculating distance. In the example below, we use a radius of 10kb and as measured from the center of pixels using the Manhattan distance. Importantly, users can also provide a ‘column’ argument for how to choose which pixel to use as the consensus pixel. In this case, we choose the pixel with the highest peak analysis score (from SIP).\n\nOnce clustered, ‘mergePairs()’ selects a representative pixel for each cluster using either the metadata column provided or, if ‘column=NULL’, the median of modes. Before using ‘mergePairs()’, there were 20,661 loops called across conditions and after merging loops, we have 16,491.\n\n\n\nTo determine which loops exhibit a change in contact frequency between conditions, we next need to extract the Hi-C contacts for each loop pixel across each of our replicates and conditions. This is accomplished using the ‘mariner’ function ‘pullHicPixels()’.\n\n\n\nTo view the count matrix, we can use the ‘counts()’ function. To increase our power to detect differential loops, we filter for loops that have at least 10 counts in at least 4 samples.\n\n\n\n\n\nNext, we use ‘DESeq2’ to detect loop pixels that exhibit a statistically significant change in contact frequency between conditions. ‘DEseq2’ requires three pieces of information to run: 1) a count matrix where each row represents a loop and each column represents a Hi-C replicate sample, 2) a ‘data.frame’ called ‘colData’ that contains experimental and technical information about the samples (columns of the counts matrix), and 3) a design formula that describes the way the variables in colData will be used to model the counts.\n\nWe constructed our counts matrix above using the ‘pullHicPixels()’ mariner function. We construct our ‘colData’ data frame which describes each sample's genotype and assigned replicate number using base R functions.\n\nWe build a ‘DESeq’ dataset and test for significant changes in loop pixel counts between the “WT” and “FS” conditions. The design formula specifies the major sources of variation to control for, as well as, the covariate to test for during differential loop calling. The last factor entered in the formula should be the condition of interest, as it will be the default factor that is tested by functions called later:\n\n\n\nTo generate more accurate ‘log2foldchange’ (LFC) estimates, ‘DESeq2’ and ‘apeglm’46 implement shrinkage of the LFC estimates toward zero when the information for a feature is low, e.g. when the counts are low or highly variable (high dispersion). As with the shrinkage of dispersion estimates, LFC shrinkage uses information from all features to generate more accurate estimates. Specifically, the distribution of LFC estimates for all features is used (as a prior) to shrink the LFC estimates of genes with little information or high dispersion toward LFC estimates closer to zero. We can get shrunken LFC estimates with the code shown below:\n\n\n\nIt is important to ensure that individual samples and replicates didn’t significantly skew our results. Principal Component Analysis (PCA) is a technique used to emphasize variation and bring out strong patterns in a dataset (dimensionality reduction). ‘DESeq2’ offers a simple function to generate a PCA plot from the top 500 features as shown below (Figure 1):\n\nWe next generate an MA plot to evaluate the magnitude of fold changes and how they are distributed relative to mean expression. The ‘plotMA()’ function provided by ‘DESeq2’ displays the mean of the normalized counts versus the log2 fold changes for all loops tested, and highlights differential loops in blue (Figure 2). This allows us to assess the general distribution of effect sizes, determine their direction of effect, and provide insight into the number of differential events.\n\nDifferential loops are shown in blue.\n\nWe can add the differential output from DESeq2 back to our ‘pixels’ object, then separate WT-specific and FS-specific loops using a BH-adjusted p-value of 0.05 and log2FoldChange above or below 0:\n\nNow that we have identified differential loops between “WT” and “FS” conditions, we can visualize them with ‘plotgardener’. We can visualize the differential loop with the lowest p-value using the code shown below.\n\nFirst, we initialize a ‘plotgardener’ page:\n\nFor convenience, we make ‘pgParams’ to set parameters that are shared for all plots:\n\nWe plot our HiC data in rectangular format using ‘plotHicRectangle’, add loop call annotations with ‘annoPixels()’, and add a heatmap legend using ‘annoHeatmapLegend()’.\n\nNext, we add arrows that point to differential loops using the ‘annoPixels’ function:\n\nFinally, we add text labels, a gene track for both strands, and genomic coordinates (Figure 3):\n\nDifferential loops are highlighted black.\n\nAn advantage to using ‘plotgardener’ instead of a genome browser is the ability to create “survey plots”. Survey plots allow us to easily generate multi-page pdfs of large sets of genomic regions. In this case, we will make a 50 page pdf displaying the Hi-C data surrounding the 50 loops with the lowest p values.\n\n\nConclusion\n\nChromatin interaction data is an important modality for understanding the mechanisms of transcriptional regulation. The workflow presented here outlines the use of ‘mariner’ as a tool to manipulate, extract, and aggregate chromatin interaction data, ‘DESeq2’ to perform differential analysis of these data across conditions, samples, and replicates, and ‘plotgardener’ to explore and visualize the results.\n\nImportantly, these tools work in concert within the R/Bioconductor environment, allowing for this workflow to be modular and compatible with other R/Bioconductor packages. For example, alternative Bioconductor packages for differential testing or for visualization of genomic data could easily be used within the R/Bioconductor environment. Our workflow allows for flexible input of Hi-C and Micro-C data in the form of ‘.hic’, ‘.cool’, and ‘.mcool’ files and visualizations are amenable to customizations with ‘grid’ graphics. This workflow provides a user-friendly pipeline for new and experienced genomicists and bioinformaticians.\n\n\nPackages used\n\nHere, we report the software versions that were used to produce this workflow. To accomplish this, we run ‘sessionInfo()’:\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data & Software availability\n\nGene Expression Omnibus (GEO): The Hi-C data used in this study. Accession number GSE143465; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE143465. 6\n\nThe chromatin loop data is available as part the ‘marinerData’ package.\n\nThe source code the multipage pdf file generated by this workflow are available on GitHub: https://github.com/jpflores-13/F1000R and Archived source code: Zenodo: https://doi.org/10.5281/zenodo.13899138\n\nLicense for Github(‘plotgardener’ & ‘mariner’): MIT License\n\nLicense for Zenodo: Creative Commons Attribution 4.0 International\n\nLicense for ‘DESeq2’: LGPL (≥ 3)\n\nAll the packages used in this workflow are publicly available from the Bioconductor project (version 3.18) and the Comprehensive R Archive Network (CRAN).\n\n\nReferences\n\nZheng H, Xie W: The role of 3D genome organization in development and cell differentiation. Nat. Rev. Mol. Cell Biol. 2019 Sep; 20(9): 535–550. PubMed Abstract | Publisher Full Text\n\nWinick-Ng W, Kukalev A, Harabula I, et al.: Cell-type specialization is encoded by specific chromatin topologies. Nature. 2021 Sep x; 599(7886): 684–691. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCai D, Feliciano D, Dong P, et al.: Phase separation of YAP reorganizes genome topology for long-term YAP target gene expression. Nat. Cell Biol. 12/2019; 21(12): 1578–1589. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXiao JY, Hafner A, Boettiger AN: How subtle changes in 3D structure can create large changes in transcription. elife. 2021 Jul 9; 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGreenwald WW, Li H, Benaglio P, et al.: Subtle changes in chromatin loop contact propensity are associated with differential gene regulation and expression. Nat. Commun. 12/2019; 10(1): 1054. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhn JH, Davis ES, Daugird TA, et al.: Phase separation drives aberrant chromatin looping and cancer development. Nature. 2021 Jun 23; 1–5.\n\nLettice LA, Heaney SJH, Purdie LA, et al.: A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly. Hum. Mol. Genet. 2003 Jul 15; 12(14): 1725–1735. PubMed Abstract | Publisher Full Text\n\nPanarotto M, Davidson IF, Litos G, et al.: Cornelia de Lange syndrome mutations in NIPBL can impair cohesin-mediated DNA loop extrusion. Proc. Natl. Acad. Sci. USA. 2022 May 3; 119(18): e2201029119. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKon A, Shih LY, Minamino M, et al.: Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms. Nat. Genet. 2013 Oct; 45(10): 1232–1237. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nDavidson IF, Bauer B, Goetz D, et al.: DNA loop extrusion by human cohesin. Science. 2019 Dec 13; 366(6471): 1338–1345. Publisher Full Text\n\nSanborn AL, Rao SSP, Huang SC, et al.: Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc. Natl. Acad. Sci. USA. 2015 Nov 24; 112(47): E6456–E6465. PubMed Abstract | Publisher Full Text\n\nDavis ES, Parker SM, Kramer NE, et al.: Mariner: explore the Hi-Cs. Bioinformatics. 2024 Jun 3; 40(6). PubMed Abstract | Publisher Full Text | Free 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\nKramer NE, Davis ES, Wenger CD, et al.: Plotgardener: cultivating precise multi-panel figures in R. Bioinformatics. 2022 Mar 28; 38(7): 2042–2045. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRStudio Team: RStudio: Integrated Development Environment for R. Boston, MA: RStudio, PBC.; 2020. Reference Source\n\nDurand NC, Shamim MS, Machol I, et al.: Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments. Cell Syst. 2016 Jul; 3(1): 95–98. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHi-C Processing Pipeline – 4DN Data Portal. http\n\nHiC Data Standards and Processing Pipeline – ENCODE. http\n\nServant N, Varoquaux N, Lajoie BR, et al.: HiC-Pro: an optimized and flexible pipeline for Hi-C data processing. Genome Biol. 12/2015; 16(1): 259. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRowley MJ, Poulet A, Nichols MH, et al.: Analysis of Hi-C data using SIP effectively identifies loops in organisms from C. elegans to mammals. Genome Res. 2020 Mar; 30(3): 447–458. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGalan S, Serra F, Marti-Renom MA: Identification of chromatin loops from Hi-C interaction matrices by CTCF–CTCF topology classification. NAR Genomics and Bioinformatics. 2022 Mar 1; 4(1): lqac021. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLuzhin AV, Golov AK, Gavrilov AA, et al.: LASCA: loop and significant contact annotation pipeline. Sci. Rep. 2021 Mar 18; 11(1): 6361. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCao Y, Liu S, Ren G, et al.: cLoops2: a full-stack comprehensive analytical tool for chromatin interactions. Nucleic Acids Res. 2022 Jan 11; 50(1): 57–71. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCao Y, Chen Z, Chen X, et al.: Accurate loop calling for 3D genomic data with cLoops. Bioinformatics. 2020 Feb 1; 36(3): 666–675. PubMed Abstract | Publisher Full Text\n\nWolff J, Backofen R, Grüning B: Loop detection using Hi-C data with HiCExplorer. Gigascience. 2022 Jan 1; 11: giac061. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLagler TM, Abnousi A, Hu M, et al.: HiC-ACT: improved detection of chromatin interactions from Hi-C data via aggregated Cauchy test. Am. J. Hum. Genet. 2021 Feb 4; 108(2): 257–268. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStatistical confidence estimation for Hi-C data reveals regulatory chromatin contacts.[cited 2024 Jul 28]. Reference Source\n\nKaul A, Bhattacharyya S, Ay F: Identifying statistically significant chromatin contacts from Hi-C data with FitHiC2. Nat. Protoc. 2020 Mar; 15(3): 991–1012. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhattacharyya S, Chandra V, Vijayanand P, et al.: Identification of significant chromatin contacts from HiChIP data by FitHiChIP. Nat. Commun. 2019 Sep 17; 10: 4221. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMifsud B, Martincorena I, Darbo E, et al.: GOTHiC, a probabilistic model to resolve complex biases and to identify real interactions in Hi-C data. PLoS One. 2017 Apr 5; 12(4): e0174744. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCarty M, Zamparo L, Sahin M, et al.: An integrated model for detecting significant chromatin interactions from high-resolution Hi-C data. Nat. Commun. 2017 May 17; 8(1): 15454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOsuntoki IG, Harrison A, Dai H, et al.: ZipHiC: a novel Bayesian framework to identify enriched interactions and experimental biases in Hi-C data. Bioinformatics. 2022 Jul 11; 38(14): 3523–3531. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang X, Xu J, Zhang B, et al.: Genome-wide detection of enhancer-hijacking events from chromatin interaction data in rearranged genomes. Nat. Methods. 2021 Jun; 18(6): 661–668. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXu Z, Zhang G, Jin F, et al.: A hidden Markov random field-based Bayesian method for the detection of long-range chromosomal interactions in Hi-C data. Bioinformatics. 2016 Mar 1; 32(5): 650–656. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCrowley C, Yang Y, Qiu Y, et al.: FIREcaller: Detecting frequently interacting regions from Hi-C data. Comput. Struct. Biotechnol. J. 2020 Dec 29; 19: 355–362. Publisher Full Text\n\nSalameh TJ, Wang X, Song F, et al.: A supervised learning framework for chromatin loop detection in genome-wide contact maps. Nat. Commun. 2020 Jul 9; 11(1): 3428. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFlyamer IM, Illingworth RS, Bickmore WA: Coolpup.py: versatile pile-up analysis of Hi-C data. Bioinformatics. 2020 May 15; 36(10): 2980–2985. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRoayaei Ardakany A, Gezer HT, Lonardi S, et al.: Mustache: multi-scale detection of chromatin loops from Hi-C and Micro-C maps using scale-space representation. Genome Biol. 2020 Sep 30; 21(1): 256. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMatthey-Doret C, Baudry L, Breuer A, et al.: Computer vision for pattern detection in chromosome contact maps. Nat. Commun. 2020 Nov 16; 11(1): 5795. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee S, Cook D, Lawrence M: plyranges: a grammar of genomic data transformation. Genome Biol. 2019 Jan 4; 20(1): 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLun ATL, Perry M, Ing-Simmons E: Infrastructure for genomic interactions: Bioconductor classes for Hi-C, ChIA-PET and related experiments. F1000Res. 2016 May 20; 5: 950. Publisher Full Text\n\nZhu A, Ibrahim JG, Love MI: Heavy-tailed prior distributions for sequence count data: removing the noise and preserving large differences. Bioinformatics. 2019 Jun 1; 35(12): 2084–2092. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNeuwirth E: ColorBrewer Palettes [R Package RColorBrewer Version 1.1-3].April 2022. Reference SourceReference Source\n\nExtension of “data.frame” [R package data.table version 1.15.4].2024 Mar 30. Reference Source"
}
|
[
{
"id": "343622",
"date": "14 Dec 2024",
"name": "Benjamin Soibam",
"expertise": [
"Reviewer Expertise Computational genomics",
"Biological Data Science",
"Applied Machine learning to understand 3D genome organization."
],
"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 provide a workflow/tool to identify and visualize differential chromatin loops from Hi-C data from two biological conditions. The tool uses existing packages in R such as the ‘mariner’, ‘DESeq2’ and ‘plotgardener’.\n3D chromatin data has been widely used to understand infer genome function. The authors have provided a workflow to compare 3D genome organization data from two conditions. This can help identify differences between the two conditions at the chromatin organization level. This tool will be very useful for many who are interested in understanding the rules govern 3D genome function and and its role in cellular processes.\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": []
},
{
"id": "346527",
"date": "23 Dec 2024",
"name": "Vanessa Vermeirssen",
"expertise": [
"Reviewer Expertise Computational biology"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper describes a workflow for identifying and visualizing differential chromatin loops from Hi-C data from two biological conditions using the ‘mariner’, ‘DESeq2’ and ‘plotgardener’ Bioconductor/R packages. It is technically sound and clearly described. The only comment I have is to add more details to “Evaluating differential results”: When do you conclude from the PCA that samples/replicates are skewing the results? Is top 500 features enough to plot? Also provide a result interpretation sentence for Figure 2.\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": []
},
{
"id": "346522",
"date": "24 Dec 2024",
"name": "Raúl de Haro Blázquez",
"expertise": [
"Reviewer Expertise Genomics - Epigenomics - Bioinformatics"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary of the article: The authors present a workflow that integrates three distinct packages to handle interaction data, perform loop differential analysis, and visualize the results. They provide an example using data from a previous study to demonstrate the workflow's application.\nIs the rationale for developing the new method (or application) clearly explained? Yes, the authors clearly articulate the need for a well-structured combination of packages to address downstream analysis for Hi-C data. Is the description of the method technically sound? Yes, the authors provide a detailed explanation of the three different packages used in their workflow. Are sufficient details provided to allow replication of the method development and its use by others? Yes, the article offers comprehensive information to enable others to replicate the method. If any results are presented, are all the source data underlying the results available to ensure full reproducibility? Yes, the data and plots are accessible on GitHub and can be easily reproduced by following the code provided in the article.\nAre the conclusions about the method and its performance adequately supported by the findings presented in the article? Partly. The Conclusions section reiterates the individual conclusions of each package which are commented in the “Results” section . As the authors are presenting a workflow, a \"tool\" for manipulating interaction data, they should include a global conclusion about the workflow itself, highlighting the advantages of combining these specific three packages over using alternatives.\n\nMinor Comments Introduction: For a broader audience, it would be beneficial to provide more information about the biology behind the formation of the oncogenic fusion protein. The importance of selecting this specific protein becomes clearer upon consulting reference (6). Methods: The authors mention that \"this workflow assumes that the majority of loops are not changing between conditions.\" How does this apply to situations where we need to compare two different cell types (e.g., two related cell types in a differentiation process) without information on the extent of shared interactions? They should address this scenario or offer an alternative differential analysis method. Use Cases: - Experimental Data: It would be helpful if the authors provided mock Hi-C files for easy download, allowing users to replicate the workflow more conveniently. - Extracting Hi-C Counts: The authors suggest filtering out data with fewer than 10 counts. They should explain why they chose a threshold of 10 counts. Is this based on data distribution? If so, they should mention it.\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? Partly",
"responses": []
},
{
"id": "346529",
"date": "31 Dec 2024",
"name": "Frank Johannes",
"expertise": [
"Reviewer Expertise epigenomics"
],
"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 an R-based pipeline to visualize (differential) chromatin loops using processed .hic (or .cool/.mcool) files. The final output consists of heatmap-like plots comparing chromatin loops between two conditions (e.g., wild-type NHA9 (WT) and mutant NHA9 (MT)) within a defined genomic range. The pipeline can be applied to other comparisons with appropriate Hi-C data. While the pipeline is well structured, modular and with clear data visualization, a few things can be improved:\nMajor Points:\nLack of Biological Motivation. The authors mention that \"chromatin loops are crucial for gene regulation,\" but this statement lacks sufficient biological depth. Please consider expanding this section, beside your specific example of NHA9. Need for a Workflow Figure. While the paper describes the workflow in text, a small schematic figure illustrating the pipeline would capture more readers attention. This figure could include the inputs (e.g., .hic files), processing steps (e.g., loop extraction, differential analysis), and outputs (e.g., heatmaps, survey plots). Lack of Comparison with Other Visualization Tools. It is not clear why one should use this R-based pipeline over other existing visualization tools like genome browsers or Hi-C heatmap generators like Juicebox and HiGlass. While the survey plot feature is highlighted as an advantage, it seems primarily focused on saving time. Are there additional benefits? A small comparison with other existing loop visualization methods would be beneficial.\n\nMinor Edits:\nCritical Typo. The first command wget -c is missing a space after -c. Without this, the downloads fail. Unspecified Dependency. It was necessary to load the library(XML) to run the pipeline successfully. Please verify and include this dependency if required. Clarify Dataset Labels. The manuscript contrasts wild-type NHA9 (WT) with a mutant (MT), but the meaning of \"FS\" in the filenames is not explained.\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": []
}
] | 1
|
https://f1000research.com/articles/13-1346
|
https://f1000research.com/articles/13-1344/v1
|
08 Nov 24
|
{
"type": "Review",
"title": "Migration, Urbanism and Health: Moving Toward Systems-Informed Policy and Practice",
"authors": [
"Palmira Immordino",
"Rita Sà Machado",
"Sally Hargreaves",
"Furio Honsell",
"Karen Lau",
"Stefania Pascut",
"Irene Torres",
"Yang Xiao",
"Anna Ziersch",
"Cathy Zimmerman",
"Rita Sà Machado",
"Sally Hargreaves",
"Furio Honsell",
"Karen Lau",
"Stefania Pascut",
"Irene Torres",
"Yang Xiao",
"Anna Ziersch",
"Cathy Zimmerman"
],
"abstract": "Migration and displacement are pivotal determinants of urban health, influencing both direct and indirect health outcomes. Migrants may face unique health risks, often exacerbated by economic, social, and environmental factors encountered during transit or upon resettlement. As migration patterns shift due to geopolitical, climatic, and economic pressures, they reshape the global and urban policy landscapes in unpredictable ways, presenting challenges that will continue to evolve in the coming decades. Current legal frameworks, in many cases, do not adequately account for migrant populations, hindering policy responses and complicating the protection of migrant health. Therefore, effective urban health interventions must be inclusive of migrant populations and expand beyond healthcare services. A systems-thinking approach that recognizes the broader determinants of health—including housing, employment, social services, and urban infrastructure—is essential to address the intersecting challenges migrants face. Despite these challenges, migration remains crucial to the functioning of urban environments. Migrant workers consistently contribute to the healthy operation of cities, underpinning key infrastructure and services. However, to optimize policy responses and improve urban health outcomes, more robust data and evidence on the health risks and outcomes of migrants, as well as the structural drivers of migration, are needed. Moreover, macro factors such as climate change, future pandemics, and geopolitical shifts are likely to influence both migration dynamics and migrant health. To anticipate and respond to these evolving challenges, a systems-informed and holistic vision of urban health is required—one that integrates migration into the broader urban policy and planning frameworks to foster healthier, more resilient cities.",
"keywords": [
"Migrant health",
"Migration and displacement",
"Urban policy and migration",
"Health determinants",
"Public health",
"Migrants",
"Refugees"
],
"content": "Content sections\n\n\n\n1. Key messages\n\n2. Introduction\n\n3. Findings\n\n4. Priority data and research\n\n\n1. Key messages\n\n\n\n- Migration and displacement are key determinants of urban health, both via direct exposures to health risks and as mediated by social or economic factors experienced by those on the move.\n\n- Migration and displacement are changing the global and urban policy landscape in significant and unpredictable ways and will continue to do so in coming decades.\n\n- Pre-existing legal frameworks often do not account for migrant populations, complicating policy responses to ongoing migration.\n\n- Migrant-inclusive urban health interventions must go beyond health services and address the multiple, wider, intersecting systems that influence health risks and outcomes.\n\n- Migration and migrant workers consistently contribute to the healthy functioning of cities and urban infrastructures.\n\n- Responding to the challenges and opportunities posed by migration requires more robust evidence on migrant health risks and outcomes and the structural drivers of population mobility.\n\n- A systems-informed, holistic vision of how migration interacts with other urban systems is fundamental to achieving the best urban health outcomes.\n\n- Climate change, future pandemics, and geopolitics are among the macro factors that shape migration dynamics and migrant health outcomes; more work is needed to understand short and longer-term future impacts.\n\n\n2. Introduction\n\nMigration and displacement have become increasingly salient issues in the global health landscape. The vulnerabilities and opportunities associated with mobility and urbanization need to be better addressed and accounted for, particularly given that migrants and displaced people represent a heterogeneous group with varied circumstances, experiences and contributions.\n\nAsylum seeker. A person who is seeking international protection.1 Prior to being granted legal status in the destination country, refugees are termed asylum seekers. Not all asylum seekers will be granted refugee status.\n\nRefugee. According to the 1951 United Nations Convention and its 1967 Protocol Relating to the Status of Refugees, under international law and UNHCR’s mandate, refugees are individuals living outside their countries of origin who are in need of international protection because of feared persecution, or a serious threat to their life, physical integrity or freedom in their country of origin as a result of persecution, armed conflict, violence or serious public disorder.2\n\nMigrant. According to the IOM, a migrant is an “umbrella term, not defined under international law, reflecting the common lay understanding of a person who moves away from his or her place of usual residence, whether within a country or across a border, temporarily or permanently, and for a variety of reasons”.3\n\nInternal migrant. A person who has moved within internationally recognized state borders and includes rural-to-rural migration and rural-to-urban migration.4\n\nlnternational migrant. Defined by the United Nations Department of Economic and Social Affairs as any person who changes his or her country of usual residence.5\n\nMigration and displacement are key determinants of health, potentially affecting epidemiological patterns of chronic and infectious diseases, mental health issues, among others. Additionally, migrants and displaced persons may face barriers in accessing healthcare and other basic services (e.g., water, sanitation, housing, safe and nutritious food, safe and fair employment) due to language, cultural, or economic factors. They may have elevated risks of injury, either during the migration journey or because of unsafe living or working conditions at their destination country.\n\nMigration to urban areas, whether between or within countries, is a defining issue for cities. Increasingly, urban health planning is considering migration patterns, migrant health characteristics and migrant-inclusive services. While global dialogue often focuses on international migration, internal migration, especially in low- and middle-income countries (LMICs), is more prevalent. Specifically, rural to urban migration is a modern feature of LMICs, particularly given the impending effects of climate change and loss of rural livelihood options.\n\nThis paper explores the relationships between migration and urban health and outlines potential implications for policy and practice. It examines how urban health advocates, practitioners and migrants themselves might respond to migration challenges and considers holistic approaches to urban health in the context of migration.\n\n\n3. Urban health and migration: what do we know?\n\nThe global movement of people, whether within borders or across them, is growing. As of 2020, worldwide estimates indicated that roughly 281 million individuals were international migrants, making up 3.6% of the global population. This number represented an increase of 128 million from 1990 and was over three times the estimated count in 1970.6\n\nMigration is determined by various determinants or drivers of individual and population mobility. The decision to migrate is influenced by circumstances in countries of origin, transit, and destination. Drivers of migration include economic, demographic, environmental, social, and political factors. People often move to improve their quality of life, access better opportunities for work or education, or escape conflict, violence, instability, persecution, or crises. Because urban centers are often seen as providing opportunities and better security, migration can contribute significantly to urban expansion.\n\nThe various types of migration contribute differently to urban growth and diversity in various contexts. International migration contributes to cultural diversity in high-income countries. Immigration adds to urban population growth, and in some contexts more so than growth from natural increase. Where both are high, as in some low-income countries, exceptionally high rates of urban growth are observed.\n\nFrequently, migrants in megacities live in informal settlements and makeshift camps and, increasingly, intermediary cities also let unplanned settlements grow unchecked. Such living conditions place migrant populations at risk of poor health outcomes. More importantly, a lack of anticipatory planning, zoning, and building of infrastructure can lead to the costly and inefficient extension of services and more adequate shelter as an afterthought.7 In addition, policy fragmentation across local and national levels may discourage health-oriented urban planning if city governments responsible for other essential services are not as accountable for health as are national health authorities.\n\nCurrent estimates indicate that 169 million people are international migrant workers8 – a figure that does not include the millions of internal migrant workers, nor refugees and forcibly displaced populations who become migrant workers in urban areas. And yet, extraordinarily little attention, and less action, focuses on migrant workers, despite figures that indicate that migrant workers are more than three times more likely than non–migrants to be in conditions of forced labour.9 A systematic review found that compared with non-migrant workers, migrant workers were 45% less likely to use any health services.10 Migrant workers, whether cross-border or internal migrants, are also over-represented in industries exposed to higher risk of occupational injury and fatality.11\n\nAt least 10.1% of all international migrants are children, and many of them migrate unaccompanied or become separated from their parents.6 Apart from sharing the vulnerabilities experienced by adults, children in urban centers are at an increased risk of, at minimum, homelessness, becoming exposed to hunger and violence, and being coerced into panhandling and micro-trafficking.12 Although rural-urban migration is more common among younger people, growing numbers of people aged 60 years and older are moving to urban areas around the world.13\n\nThe Dahlgren and Whitehead model of the social determinants of health includes different factors that can affect and impact health – including individual, lifestyle, social and community factors and working and living conditions.13 The WHO Commission on Social Determinants of Health (2008) requested that urban governance and planning explicitly address equity, as cities can concentrate threats to health.\n\nSocial and structural determinants of health substantially influence the health and the integration of migrant populations in urban settings. For example, state regulations that fail to provide migrants with basic services, including safe housing, social protection, and healthcare, set the foundation for poor health outcomes. Other structural issues, like the segregation of migrant communities in less desirable neighborhoods on the outskirts of many cities, contribute to a lack of access to services and generate new health risks, for example those associated with long commutes or neighborhood safety or environmental hazards.\n\nIntersectional considerations often further increase risks for many migrants. For example, inequitable gender norms sustain isolation and abuses experienced by female migrants. Female migrants, especially asylum-seeking and refugee women and girls, are particularly vulnerable to physical and sexual violence14 and early or forced marriage.15 Migration-related discrimination can amplify pre-existing gender inequalities, leaving abuse survivors less able to access protection or services for sexual, reproductive, and mental health. Even where social protection is ensured, access to healthcare services may be influenced by migratory status in other ways. International migrants, especially those in marginalized situations, may face sociocultural challenges such as language barriers and lack of familiarity with the health system,16 as well as a lack of culturally appropriate services.\n\nIn some countries, “health navigator” programs train and certify community health workers to provide free assistance to migrants in their own language. Mobile phone health tools can also support the interventions of community health workers17 in countries with high mobile phone coverage, including by teaching the local language to improve health literacy. Community centers are also important health promoting sites, providing access to computers, internet, and other digital resources, for example. Here, migrants can access health information and communicate with government agencies and other organizations (including to schedule healthcare appointments). Such centers can also provide other services important to health such as safe spaces to socialize, play and engage in physical activity that may be scarce in urban environments. Ultimately, greater connectivity and community center-based engagement are also useful to encourage and support participation in the decision-making processes of government agencies and other organizations to better address the needs of migrant populations.\n\nIntegration in host communities is a significant issue for many migrants, who often experience disadvantage relative to native residents in many aspects of daily life.18 Migrant populations can encounter challenges with respect to adaptation and integration, including competition and conflict among people, groups, and cultures. Adjusting to a new urban lifestyle can mean supplementing, or at times replacing, old social support systems and cultures with new ones. Challenges like securing housing, finding work, and dealing with peer pressure from family and relatives can lead to heavy psychological burdens and resulting mental health challenges19 like anxiety, despair, tension, low self-esteem, and loss of control.20 Among the many factors affecting mental health, the social environment has been shown to have a significant impact.21\n\nSocial cohesion, which describes the degree of comradery and solidarity within a community,22 can be crucial in promoting the mental health and general wellbeing of migrants. Strong social cohesion can give people a sense of support and belonging, which can act as a protective barrier against the negative effects of trauma and displacement. Programs for linguistic and cultural orientation, community-building initiatives, and specialized mental health interventions are a few examples of supportive approaches to build cohesion. Social cohesion can affect migrants’ mental health through three general mechanisms.23 First, it can encourage health-related activities and norms and exerts social control over deviant behaviors. Second, it can promote social organization, making it simpler for people to access health services. Third, it can influence psychosocial processes like offering emotional support, raising self-esteem, and fostering mutual respect. In addition, communities where people trust one another are more likely to offer assistance and support, which can help to promote mental health.24\n\nTo promote urban health that genuinely includes migrants, changing the functioning of the health system alone, while crucial, is insufficient. For instance, reducing high risks of road traffic fatalities or respiratory disease due to air pollution among migrant workers depends not only on including them in data collection by health information systems, design of appropriate health promotion information, and access to health services, but also on policy decisions within the transport, energy, and planning sectors, among others. And, vice versa: even if health promotion activities and health services are geared to include migrant workers, services may go unused without accurate data about which groups of workers are affected and how to reach specific groups, such as day laborers, who may be reluctant to lose wages to seek care.\n\nFigure 1 proposes a migrant-inclusive urban health framework to indicate various systems that might interact to affect the health of migrants. The outer spheres of Figure 1 represent multiple systems that can affect health beyond the health system alone. At the centre are “people”, “communities,” and “cities” to indicate that these systems behave in ways that affect individual migrants, migrant subgroups (as defined by nationality, legal status, work sector, etc.) and the health patterns of urban populations of migrants and non-migrants. These systems can also influence epidemiological risk and outcome patterns (e.g., infection and non-infectious diseases, nutrition, mental health) that include or exclude migrant groups and determine how well health information systems track disease patterns. Similarly, actions of multiple systems, such as immigration systems, health systems and employment practices, often combine to determine whether migrants are exposed to health hazards, whether they know their rights and entitlements and whether they work in safe and fairly paid jobs. Finally, civil society often fills in gaps where health systems or government services are not available for migrants.\n\nThe systems framework suggests that creating inclusive urban health will require going beyond health sector services, and addressing the important integration influences, such as social networks and community engagement, which can provide highly valued psycho-social support and help communicate health-related information.25 Central to all these health-inducing factors are legal structures and budget allocation systems to support migrant health amidst increasing urbanization. Evidence suggest that these frameworks are crucial in ensuring migrant health: non-health-targeted public policies can significantly affect migrant health.26 This underscores the need for a holistic approach to migrant health that considers the broader policy environment. Policies that promote social inclusion, provide easier access to healthcare, and support economic integration can significantly improve health outcomes for migrants.\n\nA strategic and integrated approach to migration and urban health27 must rely on the recognition that migration health is influenced by decisions made at various levels, from global to local, within and beyond the health sector. The ethical challenges in these decisions impact the provision and accessibility of healthcare services; it is crucial to consider specific ethical dimensions and vulnerabilities in each context.28 Values such as solidarity, duty, equity, trust, and reciprocity, are central to addressing the health needs and rights of migrants.\n\nMoreover, migration requires effective multilevel governance of migration-related issues at local, national, and international levels. At the local level, this means building alliances and partnerships, raising awareness in the population, and supporting the development of migrants’ potential in their new home. In many contexts, the spontaneous formation of numbers of local, voluntary associations and groups is quite common, driven by a moral duty of care. These can be extremely valuable because they develop detailed knowledge and respond quickly during emergencies. Local authorities need to support and involve such groups, especially where emergencies become prolonged. Because such groups often support undocumented migrants, on the edge of legality, they may be excluded from government action, yet this may set up serious tensions and conflicts within the local population.\n\nTo address this multiplicity of influences requires a holistic approach that encompasses all aspects of migrant health, including decent housing, access to basic services, social participation, decent work, emergency preparedness, and mutual support and social cohesion with native populations. A holistic approach transcends the strictly medical aspects of health care, recognizing the importance of a broader perspective for achieving migrant health in all aspects of their lives, and therefore public health for all. Promoting healthy lifestyles and prevention among migrants is also critical to long-term health trajectories, as exemplified by the long-term experiences of the WHO Healthy Cities project.29\n\n\n4. Data and research: what evidence is needed to promote urban health equity?\n\nStrategic, integrated action to improve urban health and health equity in the context of migration requires accurate, efficient, and timely data that builds on the existing evidence base. Below we highlight priority areas for new research. In addition to those highlighted, the first WHO Global research agenda on health, migration and displacement outlines key global research priorities and acts as a framework and guide for prioritizing research in this area.30 This framework can be used as a catalyst for further research in emerging areas such as urban health and migration, and to strengthen research activities and translation into policy and practice on the topic at regional and national level.\n\nPriority research areas\n\nA local and global lens. Detailed information on local urban settings is important for understanding and developing context-specific interventions to improve urban health and health equity in the context of migration. However, understanding global factors influencing the movement of people—particularly between and within low- and middle-income countries in the Global South, which host the largest numbers of migrants—is critical not only to global and regional action but for local interventions. Cross-country research on migration and urban health would supplement focused local studies by learning across two or more countries, e.g., using comparable administrative data, to examine key questions (see below).\n\nPopulation mobility. Population mobility tracking, both between and within countries, will help understand how urban settings affect health and vice versa. Some countries have adopted dispersal policies for new arrivals, particularly for refugees and asylum seekers, seeking to deconcentrate migrant groups and to match them to available resources such as housing and health services.31 Understanding the factors driving mobility within countries, including both push and pull factors, to and away from and within urban contexts, and circular and seasonal migration is important for urban health decision-making.\n\nPandemics and other health stressors. COVID-19 had a significant effect on the flow of migration between and within countries and threw a spotlight on urban health inequities, including the role of the built and social environment and health resourcing. Data collected over the pandemic about health impacts and inequities and examining this through a migration lens are important both in terms of learning about some of the drivers of health inequities and in terms of preparedness for future health events – e.g., decision making about distribution of health infrastructure and resources and consideration of specific requirements of migrants in any public health measures.\n\nStructural drivers. Complex upstream and downstream determinants of health influence outcomes in urban settings and understanding the structural drivers of urban health inequities associated with migration will contribute to informed health decision-making. For example, policies of nation states vary regarding settlement of migrants, including refugees and asylum seekers. These policies include immigration laws (e.g., mandatory detention of asylum seekers arriving by boat in Australia or regional resettlement policies that direct new arrivals away from urban areas). Influential policies also include housing and industrial relations policies that intersect with immigration policies (e.g., lack of social housing, poor social security safety nets). The Health in All Policies approach, championed by the WHO, emphasizes that non-health sectors should consider health impacts. Examining, for example, how migration and other policies affect health would provide evidence to transform policy- related structural drivers.32\n\nAn intersectional approach. In addition to structural drivers, migration related-health inequities in urban settings are also influenced by oppression and discrimination, such as racism, sexism, agism, ableism, and heteronormativity.33 It is essential to understand how these systems impact health, both in the policies around migration and the day-to-day experiences of migrants in urban areas. For example, policies can affect housing or employment discrimination and inequitable resource distribution for health and other services that are targeted away from areas of high migration settlement.\n\nTwo-way integration. Integration is a two-way process of mutual accommodation between incoming and receiving communities and affects the health of migrants. However, research has tended to focus on the extent to which migrants are able to adapt to their new communities (e.g., securing work, housing, etc.), rather than how receiving communities may themselves adapt and change.34 Further data are required in urban settings on attitudes towards accommodation of receiving communities as well as the effectiveness of interventions to improve receiving community social environments (e.g., the Welcoming Cities initiative in Australia that accredits local areas for their efforts to promote inclusion and diversity35) and examination of the ways that employment or other systems evolve and adapt to respond to the needs of migrants.\n\nPolitical will. More evidence is needed on the social and economic impacts of migration at the levels of cities and whole societies and on how different migration policies affect a range of societal goals. A better understanding of how to secure benefits and counter potential risks from migration will inform political debates and counter xenophobia, while opening the door to more effective approaches to urban health.\n\nNature of approaches and types of data. Advocacy for improved health equity in urban settings requires the centering of lived experience, both of incoming and receiving communities, making the voices of refugees and migrants heard through participatory research approaches. It is also crucial to have intersectional and interdisciplinary approaches to data collection and analysis in migration and urban health research36 and to supplement and extend research through digital data. There are considerable opportunities to consider a range of questions regarding migration and urban health through data linkage approaches that enable existing datasets to be used to answer more comprehensive questions that span focus areas. Longitudinal research designs can answer questions about causation and time lags in relation to urban health and migration and might be considered in selected cases. Complex systems,37 and implementation science can give a unique perspective particularly on upstream determinants of health in urban settings and might facilitate the uptake of evidence-based practice and research by practitioners and policy makers.\n\n\n5. Conclusion\n\nFor urban health strategies to be effective, governments and other decision-makers must take account of the contemporary reality of population mobility and the fundamental contribution of migrants to the functioning of cities and urban health. To promote inclusive urban health responses, decision-makers must remain alert to practical health-promoting strategies that do not expect migrants to reach the services, but instead reach out to migrants where they live and work, including interventions such as outreach initiatives and mobile clinics, as well as ensuring that policy settings are reflective of people’s needs.\n\nRecognizing the social determinants of health of migrants who may be exposed to multiple health risks, also means adopting systems science perspectives.38 Systems science perspectives recognise the complexity of health influences and the interactions between health intervention opportunities. To promote urban health that includes mobile populations, strategies need to go beyond narrow ‘health systems’ approaches by harnessing the interactions between the many health-influencing systems (e.g., immigration, financial, social, political). Evidence repeatedly indicates that establishing good coordination between these multiple systems will help advance migrant-inclusive urban health responses.39\n\nAmong the greatest risks to inclusive urban health in most settings are the political winds that fuel the fires of discrimination against diversity. Xenophobic and exclusionary rhetoric readily hinders the gears of those systems that could be including migrants in one-health strategies. Future urban health depends on building political will for change and on migrants and non-migrants joining together to design systems strategies that treat health as a mutual priority, because “there is no they but only us”.\n\nTherefore, to promote urban health, it is fundamental to prioritize migrants’ health by ensuring policies that are built on evidence-informed decision-making.\n\n\nEthics and consent\n\nEthics and consent not required for the performed study",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nGlossary on migration. Geneva: International Organization for Migration; 2019. Reference Source\n\nConvention and protocol relating to the status of refugees. Geneva: Office of the United Nations High Commissioner for Refugees; 1951. (United Nations General Assembly Art. 1(A)(2). Reference Source\n\nWHO is a migrant? Geneva: International Organization for Migration; 2022. Reference Source\n\nMaster glossary of terms. Geneva: Office of the United Nations High Commissioner for Refugees; 2022. Reference Source\n\nInternational migration report 2017: highlights. New York: United Nations Department of Economic and Social Affairs; 2017. Reference Source\n\nWorld Migration Report 2024 | IOM Publications Platform.\n\nMigration and Its Impact on Cities: World Economic Forum.Reference Source\n\nILO: Global Estimates on International Migrant Workers – Results and Methodology.2021.\n\nILO, Walk Free, IOM: Global Estimates of Modern Slavery: Forced Labour and Forced Marriage.2022.\n\nPega F, Govindaraj S, Tran NT: Health service use and health outcomes among international migrant workers compared with non-migrant workers: A systematic review and meta-analysis. PLoS One. 2021; 16(6): e0252651. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHargreaves S, Rustage K, Nellums LB, et al.: Occupational health outcomes among international migrant workers: a systematic review and meta-analysis. Lancet Glob. Health. 2019; 7(7): e872–e882. PubMed Abstract | Publisher Full Text | Free Full Text\n\nInter-Agency Coordination Platform or Refugees and Migrants from Venezuela. http\n\nDahlgren G, Whitehead M: The Dahlgren-Whitehead model of health determinants: 30 years on and still chasing rainbows. Public Health. 2021; 199: 20–24. PubMed Abstract | Publisher Full Text\n\nGonçalves M, Matos M: Prevalence of Violence against Immigrant Women: A Systematic Review of the Literature. J. Fam. Violence. 2016; 31: 697–710. Publisher Full Text\n\nFan S, Koski A: The health consequences of child marriage: a systematic review of the evidence. BMC Public Health. 2022; 22: 309. PubMed Abstract | Publisher Full Text | Free Full Text\n\nO’Donnell CA, et al.: Reducing the health care burden for marginalised migrants: The potential role for primary care in Europe. Health Policy. 2016; 120(5): 495–508. PubMed Abstract | Publisher Full Text\n\nEarly J, Gonzalez C, Gordon-Dseagu V, et al.: Use of Mobile Health (mHealth) Technologies and Interventions Among Community Health Workers Globally: A Scoping Review. Health Promot. Pract. 2019; 20(6): 805–817. PubMed Abstract | Publisher Full Text\n\nHerz M, Johansson T: The experience of being stopped: Young immigrants, social exclusion and strategies. Young. 2012; 20: 157–176. Publisher Full Text\n\nAvenarius CB: Immigrant networks in new urban spaces: Gender and social integration. Int. Migr. 2012; 50: 25–55. Publisher Full Text\n\nHatzenbuehler ML, Prins SJ, Flake M, et al.: Immigration policies and mental health morbidity among Latinos: A state-level analysis. Soc. Sci. Med. 2017; 174: 169–178. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBerkman LF, Glass T, Brissette I, et al.: From social integration to health: Durkheim in the new millennium. Soc. Sci. Med. 2000; 51: 843–857. PubMed Abstract | Publisher Full Text\n\nBerkman LF: Social support, social networks, social cohesion and health. Soc. Work Health Care. 2000; 31: 3–14. Publisher Full Text\n\nKawachi I, Berkman L: Social cohesion, social capital, and health. Social epidemiology. 2000; 174: 290–319.\n\nHong S, Zhang W, Walton E: Neighborhoods and mental health: Exploring ethnic density, poverty, and social cohesion among Asian Americans and Latinos. Soc. Sci. Med. 2014; 111: 117–124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAger A, Strang A: Understanding Integration: A Conceptual Framework. J. Refug. Stud. 2008; 21(2): 166–191. Publisher Full Text\n\nJuarez SP, Honkaniemi H, Dunlavy AC, et al.: Effects of non-health-targeted policies on migrant health: a systematic review and meta-analysis. Lancet Glob. Health. 2019; 7(4): e420–e435. Publisher Full Text\n\nWHO World report on the health of refugees and migrants. http\n\nWild V, Dawson A: Migration: a core public health ethics issue. Public Health. 2018 May; 158: 66–70. PubMed Abstract | Publisher Full Text\n\nOpolot J: Samson: “Building Healthy Cities: Improving the Health of Urban Migrants and the Urban Poor in Africa.” Migrants and Public Health in Uganda: From “Pathogens” to Agents of Public Health Care Development.2002.\n\nGlobal research agenda on health, migration and displacement. Geneva: WHO; 2023.\n\nOliver C, Dekker R, Geuijen K, et al.: Innovative strategies for the reception of asylum seekers and refugees in European cities: multi-level governance, multi-sector urban networks and local engagement. CMS. 2020; 8: 30. Publisher Full Text\n\nJuárez SP, Honkaniemi H, Dunlavy AC, et al.: Effects of non-health-targeted policies on migrant health: a systematic review and meta-analysis. Lancet Glob. Health. 2019; 7(4): e420–e435. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBauer GR: Incorporating intersectionality theory into population health research methodology: challenges and the potential to advance health equity. Soc. Sci. Med. 2014; 110: 10–17. PubMed Abstract | Publisher Full Text\n\nPhillimore J: Refugee-integration-opportunity structures: Shifting the focus from refugees to context. J. Refug. Stud. 2021; 34(2): 1946–1966. Publisher Full Text\n\nWelcoming Cities. http\n\nPonce NA, Shimkhada R, Adkins-Jackson PB: Making Communities More Visible: Equity-Centered Data to Achieve Health Equity. Milbank Q. 2023; 101(S1): 302–332. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSiegenfeld AF, Bar-Yam Y: An Introduction to Complex Systems Science and Its Applications. Complexity. 2020; 2020: 1–16. Publisher Full Text\n\nLuke DA, Stamatakis KA: Systems science methods in public health: dynamics, networks, and agents. Annu. Rev. Public Health. 2012 Apr; 33: 357–376. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpitzer DL, Torres S, Zwi AB, et al.: Towards inclusive migrant healthcare. BMJ. 2019 Sep 16; 366: l4256. Publisher Full Text"
}
|
[
{
"id": "345692",
"date": "31 Dec 2024",
"name": "Johannes Bhanye",
"expertise": [
"Reviewer Expertise Migration",
"urban studies",
"climate change"
],
"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 makes significant contributions to understanding the complex relationship between migration, urbanism, and health. These suggestions can enhance the depth and clarity of the analysis, ensuring that it effectively communicates its findings and implications to an interdisciplinary audience of researchers, policymakers, and practitioners in the field of urban health.\n\nConsider refining the abstract to include a brief mention of the methodological approach or specific case studies if any were used. The introduction could benefit from a more detailed discussion on how urban health challenges are uniquely modified by migration, possibly by providing a few global examples. Consider mentioning the scope of the paper early on, such as geographic focus, if applicable, or specific types of migration (e.g., rural-to-urban, international). Also be specific about the type of migration. International? The paper could be more impactful by incorporating case studies or examples that illustrate the key points. This would not only break down the theoretical content but also provide practical insights into how these challenges are managed in different urban settings. Suggest a clearer outline of gaps in current research and how addressing these could inform better policy-making. This section would benefit from a critical analysis of the limitations in existing studies on migration and urban health. It would be useful to propose specific methodologies for future research, such as longitudinal studies or mixed-methods approaches, to address the complex dynamics of migration and health. The conclusion could be strengthened by explicitly linking back to the key messages introduced at the beginning and discussing how the findings support these messages. Propose in the conclusion a few strategic recommendations for policymakers, urban planners, and health professionals on integrating migration considerations into urban health strategies. Check for grammatical errors and syntax issues that could hinder the readability of the paper.\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? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1344
|
https://f1000research.com/articles/13-517/v1
|
20 May 24
|
{
"type": "Research Article",
"title": "Association between Hematological Parameters and Severity of Covid-19 Infections",
"authors": [
"Gokul Krishnan",
"Shubhada Karanth",
"Sudha Vidyasagar",
"Archit Aggarwal",
"Anurupa Udupi",
"Suresh Karanth",
"Shivashankara Kaniyoor Nagri",
"Gokul Krishnan",
"Sudha Vidyasagar",
"Archit Aggarwal",
"Anurupa Udupi",
"Suresh Karanth",
"Shivashankara Kaniyoor Nagri"
],
"abstract": "Background This study aimed to determine the relationships between hematological parameters- hemoglobin, Total Leucocyte Counts (TLC), platelet counts, Absolute Neutrophil Counts (ANC), Absolute Lymphocyte Counts (ALC), Neutrophil Lymphocyte Ratio (NLR), Systemic Immune Inflammatory Index (SII), Neutrophil Monocyte Ratio (NMR), Platelet Lymphocyte Ratio (PLR) and the severity of COVID 19 infections and their use in predicting severity of COVID-19 infections.\n\nMethods and Material This was a prospective, observational, single-center study of 573 symptomatic adult inpatients of COVID 19 admitted to our tertiary care center.\n\nStatistical analysis used The above-mentioned hematological parameter levels were noted and compared between the two categories of COVID-19 infection, namely non-severe and severe COVID-19 using logistic regression methods. Their cut-off values were detected using the ROC curve.\n\nResults The median TLC, ANC, NLR, SII, NMR, PLR were notably higher in patients with severe COVID-19 than in those with non-severe COVID-19. Logistic regression analysis showed that NMR (OR=1.029, p=0.006) and ALC (OR=0.999, p=0.002) were statistically significant independent predictors of COVID-19 severity\n\nConclusions The hematological parameters mentioned, can be used for predicting severe COVID-19 infections at admission. ALC and NMR levels could be used as hematological markers to predict severity of COVID-19 in adult patients with their cut off values being < 1105 cells/cubic millimeter and > 10.434 respectively.",
"keywords": [
"COVID-19",
"Droplet spread",
"Inflammation",
"Hematological",
"Pandemic",
"SARS-CoV-2"
],
"content": "Introduction\n\nIn early December 2019, the world saw the beginning of an epidemic of the new coronavirus disease 2019 (COVID-19), due to the newfound virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 later evolved into a pandemic that affected billions of people worldwide. Measures taken for social distancing and the impact of the disease on socio-economic status, morbidity, and mortality have proven to be a major burden on millions of people all over the world.1\n\nIndia saw its first case in Kerala in late January 2020.2 India with a total of 430422 active cases as of 16/07//2021 as per the Ministry of Health and Family Welfare, Government of India website.3 Mortality rates due to the disease have varied from 3% in China to 145% in some cities in Mexico.4,5 India has a mortality rate of 1.33% as of 16/07/2021.3 A resurgence has been noted with JN1 as the new variant with high immune evasion properties.6 Thus, simple tools for triaging and prognosticating COVID-19 are needed. Studies on hematological parameters of COVID-19 in our country are scarce. This study is a modest attempt to study the association of basic hematological parameters such as total leukocyte count, neutrophil-to-monocyte ratio (NMR), neutrophil to lymphocyte ratio (NLR), Systemic Inflammatory Index (SII), and platelet-to-lymphocyte ratio (PLR), which can be easily availed even in rural setups, with the severity of COVID-19, which might aid in the evaluation of patients and in detecting the progression to severe disease at the time of admission. This may even help in the judicious triaging of patients at the time of admission.\n\n\nMethods\n\nA prospective observational study was conducted by clinical examinations and lab investigation in the Department of Internal Medicine, at a tertiary care hospital, in Karnataka, India for a period of three months from 03/12/2020 to 25/03/2021.\n\nThe study was approved by our Institutional Review Board (IRB) known as Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (reference number: 740/2020). It was approved on 3rd December, 2020 for a period of three months till 31st March 2021. This study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was waved and telephonic verbal consent was taken citing restrictions during COVID-19. The same was approved by the Institutional Ethics Committee. The data collected were kept confidential.\n\nAll symptomatic adult COVID-19 patients who were admitted to our tertiary care facility in Karnataka, India, and whose diagnoses were made by nasopharyngeal swab RT-PCR were included in this prospective study. The inclusion criteria were hospital admissions of patients who tested positive for COVID-19 by RT-PCR and were at least 18 years of age.\n\nPatients with the following conditions were not included in the study: patients with known cases of sepsis or other associated infections at the time of COVID-19 diagnosis; patients with diagnosed cases of cytopenia, including autoimmune cytopenia, Evans disease, and ITP; patients with diagnosed cases of congenital or acquired bone marrow failure; patients with diagnosed cases of primary haematological malignancies or malignancies involving bone marrow; and patients who were discharged against medical advice.\n\nA total of 622 patients were included in this study. Even so, nine patients declined to take part in the study, four individuals revoked their consent while receiving treatment at the hospital, and 27 people were excluded from the study altogether. Nine patients were discharged against medical advice.\n\nFinal sample size in this study was 573.\n\nThe study collected demographic information including age and sex; clinical data including symptoms; a history of comorbidities including diabetes mellitus, essential hypertension, chronic kidney disease, diagnosed malignancies, and ischemic heart disease; as well as the results of general and systemic examinations. A complete blood profile, arterial blood gas analysis (ABG), liver and renal function tests, an electrocardiogram, and a chest X-ray were among the laboratory investigations performed. Further examinations were conducted in adherence to the protocol prescribed.\n\nNormal hemoglobin levels were taken as - 12-15 g/dL, total leukocyte counts as those between 4000-10000 cells per cubic millimeter, neutrophil counts as 2000-8000 cells per cubic millimeter, lymphocyte counts as 720-4400 cells per cubic millimeter, and platelet counts as 150000-400000 cells per cubic millimeter.\n\nAll COVID-19 patients in the study were classified as mild, moderate, severe and critical COVID-19 at the time of admission. This was done using the national guidelines provided by the Indian Council of Medical Research, which was similar to the WHO guidelines.7 Those with mild symptoms maintaining oxygen saturation >90% on room air were considered to be in the non-severe category. The patients with moderate, severe and critical symptoms who required oxygen supports and/or required intensive care unit admission were classified as severe.\n\nThe patients were periodically reviewed during their in-hospital stay, and the highest degree of disease severity was considered when classifying the cohorts.\n\nNasopharyngeal throat swabs for COVID-19 RTPCR were obtained from all patients enrolled in the study in the hospital virology laboratory using the TRUPCR RT qPCR kit. It is a reagent system based on real-time PCR technology for the detection of diseases.\n\nThe protocol established by the ICMR (Indian Council of Medical Research) were used for performing RT-PCR assays. This was in accordance with the WHO guidelines.\n\nEDTA whole-blood samples were used for complete blood counts.\n\nThe Systemic Immune Inflammatory Index was calculated using the formula - Neutophil counts/Lymphocyte counts and platelet counts.\n\nAn analysis was conducted on all categorical variables, including underlying comorbidities and sex, and the results were presented as frequencies and percentages. When applicable, continuous variables exhibiting skewed distributions, such as TLC and ANC, were denoted using the median along with the interquartile range (Q1-Q3). Conversely, variables following normal distributions were depicted using the mean ± standard deviation. Using the Mann-Whitney U test, the difference between the medians of the non-severe and severe COVID-19 categories was analysed. By employing logistic regression analysis, the optimal parameters for predicting the severity of Covid-19 were identified. The specificity and sensitivity of the test were ascertained, as well as the cut-off values for different parameters pertaining to the non-severe and severe COVID-19 groups, utilising a receiver operating characteristic curve. The software SPSS 23.0 (IBM SPSS statistics, USA) was utilised to analyse the data.\n\n\nResults\n\nThe demographic and baseline characteristics of the patients are shown in Tables 1 and 2. Among the 573 COVID-19 patients in our study, the majority were males. In the severe category, many patients in the ICU required mechanical ventilation and non-invasive ventilation. The rest were administered oxygen supplementation via a Venturi mask, non-rebreathing masks (NRBM) and nasal prongs. Comorbidities were observed in a large number of patients. Overlap of more than one chronic illness was unavoidable in some patients.\n\n† (Mean ± Standard deviation) or in\n\n‡ Median (Q1-Q3).\n\n* Statistically significant.\n\n† Parameters subjected to logistic regression analysis.\n\nThe median values of hematological parameters such as hemoglobin, total leukocyte counts, ANC, ALC, platelets, NLR, SII, NMR, and PLR were compared, and the statistically significant values are shown in Table 3. The hematological parameters were also compared between the survivors and non-survivors of the severe category, which are depicted in the same table. The mean hemoglobin values of the non-severe and severe COVID-19 categories were compared but were found to be statistically insignificant.\n\n† (Mean ± Standard deviation) or in\n\n‡ Median (Q1-Q3).\n\n* Statistically significant.\n\nCOVID-19 patients were categorized into two groups. The non-severe and severe categories consisted of 271 and 302 patients, respectively. Statistically significant differences were only observed in patient age, sex, and associated comorbidities. Associated comorbidities were further analyzed using multivariate logistic regression, is shown in Table 4.\n\n* Statistically significant.\n\nComorbidities, such as type 2 diabetes mellitus, essential hypertension, ischemic heart disease, and the abovementioned hematological parameters, which were statistically significant, were further subjected to logistic regression (Table 4). The hematological parameters between the survivors and non-survivors in the severe category of statistical significance were also subjected to logistic regression, but none of them were statistically significant. This analysis showed that type 2 diabetes mellitus, essential hypertension, NMR, and ALC were statistically significant independent predictors of COVID-19 severity while ischemic heart disease, as an independent predictor, had borderline significance.\n\nAs there was a statistically significant difference between non-severe and severe categories in the above-mentioned hematological parameters, they were further studied using Receiver Operating Characteristic (ROC) curve analyses. Regarding the observations made by ROC analyses, the following information concerning patients with COVID-19 diagnosis severity was found (Table 5 and Figure 1).\n\n* Statistically significant values.\n\n\nDiscussion\n\nThis study was a prospective observational study that determined the mean age of the patients to be 55.82 ± 15.84 years. This conclusion aligns with earlier studies conducted in China and the USA.8–10 However, the mean age in this study was slightly higher than that reported in an Indian cohort study conducted by Nitesh Gupta and colleagues in New Delhi.11 The prevalence of the condition was higher in men (61.6%) compared to women, which is consistent with the results reported by Fei Zhou and his colleagues in China.9 Richardson et al. conducted a study in the United States using a case series of 5700 patients. Their findings revealed that the death rate for males was consistently greater than that of females in every 10-year age interval beyond 20 years.10 A total of 85.9% of patients had comorbidities. Our study found a considerable prevalence of type 2 diabetes mellitus and essential hypertension, particularly in the severe category. Our study demonstrated a marginal level of significance indicating that ischemic heart disease can be used as a predictor of the severity of COVID-19. Nevertheless, research conducted in China and the USA revealed that patients with COVID-19 were more likely to have essential hypertension as a pre-existing condition, with additional comorbidities such as type 2 diabetes mellitus and coronary artery disease following suit.8–10\n\nThe results of our investigation indicated a little elevation in the overall number of white blood cells and neutrophils in those with severe illness. This finding aligns with the retrospective study undertaken by Lin et al. and Rami M. Elshazli et al.12,13 A study conducted by Agrawal et al. in Rajasthan, India, found similar results in 102 patients who had both symptomatic and asymptomatic cases of COVID.14 However, Guan and colleagues observed a higher incidence of leukopenia (33%) in the severe group compared to the non-severe group in their analysis of 1099 COVID-19 patients in China.8 Neutrophils, monocytes, and lymphocytes, which are diverse components of white blood cell counts, have distinct functions in the immune response within our body. Neutrophils, the predominant kind of white blood cells in the peripheral blood of humans, are now recognised as having a significant impact on safeguarding the respiratory epithelium by promoting the production of pro-inflammatory cytokines in the immediate area.15 Nevertheless, it appears to have both positive and negative consequences, since excessive activation of neutrophils can lead to heightened inflammation, increased tissue damage, and hence exacerbate the disease.15,16\n\nThe results of our investigation revealed lymphocytopenia in the severe group, accompanied by a significantly elevated median NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio). W. Guan and his colleagues also observed this significant lymphocytopenia.8 Abhishek Agrawal and his colleagues in India observed a decrease in the average number of lymphocytes (20.58±0.87 vs 28.60±8.65), an increase in the average NLR (6.17±6.11 vs. 2.67±1.32), and an increase in the average PLR (146.29±88.90 vs. 115.47±47.88) among patients in the moderate to severely ill category, compared to asymptomatic and mildly symptomatic patients.14 The study conducted by Sha-Lin et al. in China demonstrated that an increased NLR (neutrophil-to-lymphocyte ratio) is a standalone predictive indicator for the severity of COVID-19.12 Lymphocytes are a specific type of white blood cells (WBCs) that play a crucial role in triggering adaptive immunity and the establishment of ‘self-tolerance’.17,18\n\nThe cytokine storm typically occurs 1-2 weeks after the infection starts, when the virus moves through the circulation and primarily targets tissues with a high concentration of ACE2, the receptor for SARS-CoV-2. During this time, there is a noticeable decrease in lymphocyte count, known as lymphopenia.19 Studies have demonstrated that lymphocytes in the blood express a limited quantity of ACE2 receptors on their surface. This is believed to be the reason of lymphopenia in COVID-19.20 Monocytes are a distinct subset of white blood cells (WBCs) found in the human body. They can be categorised into three subtypes: classical, intermediate, and non-classical.21 Recent investigations have indicated a decrease in intermediate and non-classical monocytes after SARS-CoV-2 infections.22 These monocytes have the capacity to transform into activated macrophages and exhibit both anti-inflammatory and pro-inflammatory functions due to their capability to generate certain cytokines. Therefore, reducing them may disturb this equilibrium and lead to an elevation in the immunological response.23\n\nNeutrophils, lymphocytes, and monocytes have diverse functions in the immune response during various situations, such as COVID-19 infections. Therefore, it can be inferred that an elevated NMR could indicate a disturbance in the balance of the immune system cells, perhaps indicating the severity of the disease with considerable morbidity.\n\nThe Systemic Immune Inflammatory Index (SII) has demonstrated its effectiveness as an early and convenient prognostic indicator in cases of metastatic castration resistant prostate cancer (mCRPC) and metastatic renal cell carcinoma. The study also examined its significance in predicting the outcome of stomach carcinomas.24 Our study focused on examining the correlation between SII and the severity of COVID-19. However, our analysis did not find any statistically significant relationship between the two variables. Fois et al. found a strong correlation between the SII and the severity of COVID-19. Nevertheless, the study found that the area under the curve (AUC) for the SII was only marginally significant, with a p-value of 0.060.25\n\nOur study, for the first time, shows a significant association between NMR and COVID-19 severity. The AUC also showed significance at >10.34 being the cut off value for the association of NMR with severe COVID-19 disease. NMR has not been studied extensively in previous studies and may be regarded as an easy and early prognostic marker of COVID-19 severity. This is a strength of the present study.\n\nOur study has some limitations. First, this was a single-center study with no external validation cohort. The hematological parameters studied were taken at the time of admission. It remains unclear whether stepwise changes occur when the patient’s condition worsens clinically.\n\nSeveral markers, such as coagulation parameters, D-dimer, and CRP, were not included in this investigation, which might have offered a comprehensive understanding of the severity and underlying causes.\n\n\nConclusion\n\nSeveral haematological indicators have been widely investigated for predicting the severity of COVID-19. The results of our investigation revealed a noteworthy correlation between the levels of ALC (absolute lymphocyte count), NMR (neutrophil-to-lymphocyte ratio), and the severity of COVID-19. This has enhanced the significance of our investigation, as the relationship between NMR and the severity of COVID-19 has not been fully investigated. The utilisation of ALC and NMR at modest facilities and rural hospitals inside our nation, which possess limited resources, can effectively facilitate the triage and management of patients upon admission.\n\nThe study was approved by our Institutional Review Board (IRB) known as Kasturba Medical College and Kasturba Hospital Institutional Ethics Committee (reference number: 740/2020). It was approved on 3rd December,2020 for a period of three months till 31st March, 2021. This study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was waved and telephonic verbal consent was taken citing restrictions during COVID-19. The same was approved by the Institutional Ethics Committee. The data collected were kept confidential.",
"appendix": "Data availability\n\nFigshare: Covid study dataset. DOI: https://doi.org/10.6084/m9.figshare.25299151.v1. 26\n\nThe data contains various hematological parameters in cases of Covid-19 of varying severity.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nZhu N, Zhang D, Wang W, et al.: A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020 Feb 20; 382(8): 727–733. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAndrews MA, Areekal B, Rajesh KR, et al.: First confirmed case of COVID-19 infection in India: A case report. Indian J. Med. Res. 2020 May; 151(5): 490–492. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMinistry of Health and Family Welfare, Government of India: COVID-19 India. Accessed on: 2021 April 19. Reference Source\n\nYan Y, Shin WI, Pang YX, et al.: The first 75 days of novel coronavirus (SARS-CoV-2) outbreak: recent advances, prevention, and treatment. Int. J. Environ. Res. Public Health. 2020 Jan; 17(7): 2323. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFriedman J, Calderón-Villarreal A, Bojorquez I, et al.: Excess out-of-hospital mortality and declining oxygen saturation: the sentinel role of emergency medical services data in the COVID-19 crisis in Tijuana, Mexico. Ann. Emerg. Med. 2020 Oct 1; 76(4): 413–426. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLooi MK: Covid-19: WHO adds JN.1 as new variant of interest. BMJ. 2023 Dec 21; 383: 383–2975. PubMed Abstract | Publisher Full Text\n\nMinistry of Health and Family Welfare, Government of India. Clinical management protocol for covid-19 (In adults); version 6.2021 May 24; 4–6. Accessed on May 30 2021. Reference Source\n\nGuan WJ, Ni ZY, Hu Y, et al.: Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020 Apr 30; 382(18): 1708–1720. Epub 2020 Feb 28. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhou F, Yu T, Du R, et al.: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28; 395(10229): 1054–1062. Epub 2020 Mar 11. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. Erratum in: Lancet. 2020 Mar 28;395(10229):1038. PMID: 32171076; PMCID: PMC7270627. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRichardson S, Hirsch JS, Narasimhan M, et al.: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 May 26; 323(20): 2052–2059. Erratum in: JAMA. 2020 May 26;323(20):2098. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGupta N, Ish P, Kumar R, et al.: Evaluation of the clinical profile, laboratory parameters and outcome of two hundred COVID-19 patients from a tertiary centre in India. Monaldi Arch. Chest Dis. 2020 Nov 9; 90(4). PubMed Abstract | Publisher Full Text\n\nLin S, Mao W, Zou Q, et al.: Associations between hematological parameters and disease severity in patients with SARS-CoV-2 infection. J. Clin. Lab. Anal. 2021 Jan; 35(1): e23604. Epub 2020 Nov 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshazli RM, Toraih EA, Elgaml A, et al.: Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients. PLoS One. 2020 Aug 21; 15(8): e0238160. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAgrawal A, Tyagi P, Mahavar S, et al.: Study of hematological and biochemical parameters in a cohort of Indian COVID-19 patients admitted in a tertiary care centre. Int. J. Adv. Med. 2020 Dec; 7(12): 1840–1845. Publisher Full Text\n\nHemmat N, Derakhshani A, Bannazadeh Baghi H, et al.: Neutrophils, crucial, or harmful immune cells involved in coronavirus infection: a bioinformatics study. Front. Genet. 2020 Jun 9; 11: 641. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFeng X, Li S, Sun Q, et al.: Immune-inflammatory parameters in COVID-19 cases: a systematic review and meta-analysis. Front. Med. 2020 Jun 9; 7: 301. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChaplin DD: Overview of the immune response. J. Allergy Clin. Immunol. 2010 Feb 1; 125(2): S3–S23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSakaguchi S, Yamaguchi T, Nomura T, et al.: Regulatory T cells and immune tolerance. Cell. 2008 May 30; 133(5): 775–787. Publisher Full Text\n\nLi T, Lu H, Zhang W: Clinical observation and management of COVID-19 patients. Emerg. Microbes Infect. 2020 Dec; 9(1): 687–690. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXu H, Zhong L, Deng J, et al.: High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int. J. Oral Sci. 2020 Feb 24; 12(1): 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZiegler-Heitbrock L, Ancuta P, Crowe S, et al.: Nomenclature of monocytes and dendritic cells in blood. Blood. 2010 Oct 21; 116(16): e74–e80. Publisher Full Text\n\nGatti A, Radrizzani D, Viganò P, et al.: Decrease of non-classical and intermediate monocyte subsets in severe acute SARS-CoV-2 infection. Cytometry A. 2020 Sep; 97(9): 887–890. PubMed Abstract | Publisher Full Text | Free Full Text\n\nArango Duque G, Descoteaux A: Macrophage cytokines: involvement in immunity and infectious diseases. Front. Immunol. 2014 Oct 7; 5: 491. Publisher Full Text\n\nWang Q, Zhu D: The prognostic value of systemic immune-inflammation index (SII) in patients after radical operation for carcinoma of stomach in gastric cancer. J. Gastrointest. Oncol. 2019 Oct; 10(5): 965–978. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFois AG, Paliogiannis P, Scano V, et al.: The Systemic Inflammation Index on Admission Predicts In-Hospital Mortality in COVID-19 Patients. Molecules. 2020 Dec 4; 25(23): 5725. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKrishnan G, Karanth S, Vidyasagar S, et al.: Covid study dataset. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "285245",
"date": "18 Jun 2024",
"name": "Marc Vasse",
"expertise": [
"Reviewer Expertise Biologiclal markers in COVID-19"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this paper, the authors have analyzed different hematological parameters, including ratios derived from the differential, in order to identify the severity of COVID-19; It is a retrospective study performed on 573 patients, during the first wave of COVID-19. hey observe that lymphopenia and the neutrophil to monocyte ratio is predictive of the severity of the disease. It is a well-written paper. The main problem is that is that the study is not very original, since lymphopenia was very quickly identified as a marker of severity of COVID-19, as were the different differential ratios. In addition, the authors indicate in the discussion that this is the first time that the NMR ratio has been shown as a factor in the severity of COVID-19; This is incorrect, a first article indexed in 2021 by Rizo-Téllez et al (Microorganisms. 2020 Oct 10;8(10):1560. PMID: 33050487) has already described this parameter as predictive. Finally, the question that now arises is: are these markers identified during the first wave in 2020 still relevant?\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": "12245",
"date": "02 Sep 2024",
"name": "Shubhada Karanth",
"role": "Author Response",
"response": "Dear Dr Vasse, thank you for your time and valuable input towards improving our paper. Kindly review the modifications made. After going through the article by Rizo Téllez et al according to your suggestion, we have removed our claim that our study was the first one to consider NMR ratio and have cited the study by Rizo Téllez et al. Regarding the relevance, we feel that though it may not be as relevant as before during the COVID wave, it may still its significance considering that COVID-19 is still prevalent with new variants emergin. In addition, we felt it was important to publish the findings from our center to contribute to the existing data and literature."
}
]
},
{
"id": "291337",
"date": "02 Jul 2024",
"name": "Yogesh Kumar",
"expertise": [
"Reviewer Expertise Neurophysiologist."
],
"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 addresses a timely and relevant issue with potential clinical impact. It provides valuable insights into the use of hematological parameters for predicting COVID-19 severity. With minor revisions to enhance the clarity and robustness of the findings, it would be suitable for publication. The study's novelty lies in its focus on easily accessible hematological parameters and their potential to predict COVID-19 severity, particularly in an Indian context. This is significant given the limited resources in many healthcare settings in India and other similar regions. The introduction could benefit from a more detailed discussion of previous studies that have explored similar parameters, providing a more robust rationale for the current study. The mention of the resurgence with the JN1 variant could be elaborated to explain its relevance to the study's timing and context. The method of calculating the Systemic Immune Inflammatory Index (SII) should be clearly defined. The limitations section should be expanded to discuss the impact of the single-center design and the lack of external validation in more detail. The discussion could benefit from a more thorough exploration of the clinical implications of the findings, particularly in the context of resource-limited settings.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12246",
"date": "02 Sep 2024",
"name": "Shubhada Karanth",
"role": "Author Response",
"response": "Dear Dr Kumar, we would like to thank you for your time and valuable input. We have tried our best to consider your points. Kindly consider reviewing them. Comment :The introduction could benefit from a more detailed discussion of previous studies that have explored similar parameters, providing a more robust rationale for the current study. Reply: We have included a more detailed discussion Comment: The method of calculating the Systemic Immune Inflammatory Index(SII) should be clearly defined Reply: We have added the method of calculating SII Comment: The mention of the resurgence with the JN1 Variant could be elaborated to explain its relevance to the study’s timing and context. Reply: We have elaborated on the resurgence of JN1 and its relevance as suggested. Comment: The limitations section should be expanded to discuss the impact of the single-center design and the lack of external validation in more detail Reply: We have added the points under limitations Comment: The discussion could benefit from a more thorough exploration of the clinical implications of the findings, particularly in the context of resource-limited settings Reply: We have provided a more detailed exploration of the clinical implications"
}
]
}
] | 1
|
https://f1000research.com/articles/13-517
|
https://f1000research.com/articles/13-709/v1
|
27 Jun 24
|
{
"type": "Research Article",
"title": "The Relationship Between Mental Health and Periodontal Disease: Insights from NHANES Data ",
"authors": [
"Eman AlJoghaiman"
],
"abstract": "Introduction and aim Periodontal disease, initiated by dental biofilm and influenced by various local and systemic factors, includes stress as a potential contributor to its progression. Despite associations with severe forms like acute necrotizing ulcerative gingivitis, a comprehensive large-sample study linking stress to periodontal disease is lacking. This study aims to investigate the relationship between mental health and periodontal disease.\n\nMaterials and Methods Leveraging data from the National Health and Nutrition Examination Survey (NHANES), relevant information was extracted. Mental health was the exposure variable, and periodontal disease, assessed through indices following Eke et al.'s definition, served as the outcome. Covariates impacting periodontal disease were considered, and demographic and disease status analyses employed the Rao-Scott chi-squared test. A logistic regression model assessed mental health's impact on periodontal disease.\n\nResults Logistic regression indicated higher odds of periodontal disease among individuals feeling bad about themselves for more than half of the day (OR 1.170, 95% CI 0.533-2.474), though statistical significance was not reached. Periodontitis prevalence significantly varied based on marital status, with 6.6% of married and 10.8% of unmarried subjects affected. Notably, a statistically significant difference in periodontitis prevalence existed between subjects with health insurance (8.3%) and those without (16.5%).\n\nConclusion Within study limitations, it is concluded that no significant difference exists in periodontal status between individuals with compromised mental health and those without. The findings underscore potential associations between mental health, marital status, and access to health insurance with periodontal disease.",
"keywords": [
"Stress",
"mental health",
"periodontal disease",
"NHANES"
],
"content": "Introduction\n\nPeriodontal disease is a multifaceted condition influenced by various factors. Its distinctive characteristics, site-specific progression involving complex etiological factors, and the impact of risk factors have continually spurred researchers to delve deeper into unraveling the intricacies of the disease process.1 While the disease typically begins with dental biofilm, transitioning from gingivitis to periodontitis, it's important to emphasize that not all instances of gingivitis evolve into periodontitis. Furthermore, there's notable variation in the prevalence of periodontitis within a given population, with some individuals showing no signs, others exhibiting slow progression, and some experiencing a more rapid advancement.2 Additionally, on an individual level, not every site displays clinical attachment loss and signs of periodontal disease; certain sites may present severe clinical loss of attachment coupled with bone loss.3\n\nThe diverse manifestations of periodontal disease may arise due to the intricate nature of factors influencing its progression. Both local and systemic factors can exert an influence on the development of the disease.4 Numerous systemic factors that contribute to the progression of the disease have been thoroughly elucidated. These encompass diabetes, hormonal fluctuations during puberty, pregnancy, and menopause, as well as genetic factors and conditions.5 Stress and psychological factors are also recognized contributors, impacting the overall periodontal health status and influencing disease progression.6\n\nPsychological stress refers to the emotional and physiological response individuals undergo when confronted with challenging life events. These events may include exams, adapting to new work conditions, marital conflicts, financial instability, or even profound situations like the loss of a loved one. The intensity of these situations surpasses an individual's ability to cope effectively, triggering emotional and physiological reactions. It is a significant modifiable risk factor impacting both mental and physical well-being.7,8\n\nThe term “stress” encompasses any physical or psychological event perceived as capable of causing harm or emotional distress. Stress is a ubiquitous factor in nearly all chronic diseases. Psychosocial stress is subject to modification by individual perceptions and coping strategies, involving the release of specific products through various pathways: the hypothalamic-pituitary-adrenal axis, leading to glucocorticosteroids; the autonomic nervous system, resulting in the release of catecholamines; and the hypothalamic-pituitary-gonadal axis, leading to the release of sex hormones.9 Exposure to stress during critical periods is known to alter hormonal and immune systems. The emotional or psychological burden may directly influence immune activities through nerve messenger substances or indirectly through hormones. The oral cavity, as the gateway for systemic components, is not immune to the effects of stress.10\n\nIn the pathophysiological models proposed by Genco et al. (1998), the role of stress as a risk factor for periodontal disease is thoroughly explained. Two models are presented, one detailing the direct effects and the other describing the indirect effects. The primary model posits that psychosocial stressors set off a sequence of events involving the release of corticotrophin-releasing hormone through the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and the central nervous system. These physiological responses negatively impact the immune-inflammatory cells, increasing the susceptibility to infection and, specifically, periodontal disease. The second model outlines the indirect impact of stress on health-risk behaviors such as inadequate oral hygiene, smoking, overeating, and particularly a high-fat diet, which can result in immunosuppression due to heightened cortisol production. Another potential behavioral consequence influenced by stress and inadequate coping is depression. The interplay of all these factors contributes to the progression of periodontal disease.9,11\n\nThe connection between stress and periodontal disease has long been established. Stress is linked to acute necrotizing ulcerative gingivitis, with immune-compromised conditions and poor oral hygiene as contributing factors for this acute condition.12 Stress and depression can compromise periodontal resistance, fostering opportunistic microbial growth, reducing saliva flow, and impairing gingival blood flow.13 Elevated levels of epinephrine and non-epinephrine induced by stress alter blood flow and oxygen requirements. Changes in the host response, particularly in neutrophil function, create an environment conducive to bacterial growth, including species like Prevotella intermedia and other spirochetes, leading to necrotizing ulcerative gingivitis.14 This pathogenic process is supported by increased clinical cases observed during stressful periods, such as exams in students and in individuals with demanding occupations.15 The literature also reflects a similar correlation between stress and severe periodontitis.16 Furthermore, in individuals experiencing stress, the virus is believed to reside in connective tissue, contributing to periodontal disease progression alongside other microbial complexities.17\n\nWhile studies spanning four decades exist, the number of investigations correlating stress and periodontal disease remains limited. The challenge lies in the varied definitions used to measure stress, encompassing different types of stress, psychological disorders, and various subcategories. These complexities make it challenging to clearly understand the link between stress and periodontal disease. Various types of psychological and psychosocial factors, such as high work stress, job dissatisfaction or unemployment, family status, and the impact of major life events, have been studied and found to be related to periodontal disease.18–20 However, none of these studies distinctly define this association.\n\nIn a study by Genco et al. (1999), psychosocial stress factors, coupled with financial worries, were associated with adult periodontal disease, highlighting both as risk indicators.21 Another study correlating patients with inadequate stress behavior strategies (defensive coping) with periodontal disease identified these individuals as being at a higher risk for severe periodontal disease. However, the necessity for further investigations was emphasized to elucidate their role in the progression of periodontal disease.22\n\nOccupational stress emerges as a potential risk factor for periodontal disease, as evidenced by a study conducted among police personnel. The experimental group, characterized by higher occupational index scores and serum cortisol levels, exhibited elevated plaque scores and bleeding indices compared to the control group.23 Another study by Vyas (2018) explored the correlation between stress, measured by cortisol levels, in two groups of 25 patients each with chronic periodontitis and a healthy periodontium. Significant differences were observed in plaque, probing depth, clinical attachment level, and cortisol levels, leading to the conclusion that psychosocial stress may be associated with periodontal destruction through both behavioral and physiological mechanisms.24 Despite these findings highlighting the impact of stress on periodontal disease, the direct effects remain somewhat unclear. Furthermore, existing studies underscore the need for further research to establish this impact on a larger population, considering other controlled variables. Consequently, the present study seeks to investigate the relationship between mental health (self-perception) and periodontal disease.\n\n\nMethods\n\nThe National Health and Nutrition Examination Survey (NHANES) is a comprehensive cross-sectional survey conducted in the United States, designed to offer a nationally representative overview of non-institutionalized individuals residing in households. Participants in this survey undergo a series of assessments, which include completing a questionnaire, undergoing medical and dental examinations, and participating in various laboratory tests. The protocols for collecting oral health data in the NHANES 2011–2012 and NHANES 2013–2014 cycles received approval from the Centers for Disease Control and Prevention National Center for Health Statistics Research Ethics Review Board. All survey participants provided written informed consent before publishing their information. Our study utilized data from key sections of the NHANES, encompassing demographic information, examination results, questionnaire responses, and limited access data. Specifically focusing on individuals aged 18 years and older who underwent a dental examination, we implemented exclusion criteria to exclude edentulous subjects from our analysis. This strategy ensures a thorough and targeted evaluation of oral health within a diverse and nationally representative sample of the U.S. population.\n\nExposure variable:\n\nMental health\n\nOutcome variable:\n\nPeriodontal disease\n\nFor this investigation, we used the NHANES complete periodontal examination data to calculate periodontal disease indices using definition of periodontal disease (1). According to the definition, periodontal disease was classified as follows: Severe periodontitis: >=2 interproximal sites with loss of attachment (LOA) >=6 mm (not on the same tooth) and >=1 interproximal site with probing depth (PD) >=5 mm; Moderate periodontitis: >=2 interproximal sites with LOA >=4 mm (not on same tooth), or >=2 interproximal sites with PD>=5 mm (not on same tooth); Mild periodontitis: >=2 interproximal sites with LOA >=3 mm, and >=2 interproximal sites with PD >=4 mm (not on same tooth) or one site with PD >=5 mm and finally, no periodontitis group whose has no evidence of mild, moderate, or severe periodontitis.26\n\nCovariate variable:\n\nTo ensure a comprehensive examination and control for potential influencing factors, our analysis incorporates a diverse set of covariates. These covariates play a crucial role in minimizing the impact of potential confounders, enabling a more precise scrutiny of the relationship between the exposure and outcome. The extensive list of covariates comprises age, sex, race/ethnicity, education, socioeconomic status, poverty/income ratio, marital status, occupation, smoking habits, alcohol consumption, BMI, HbA1C, dental insurance coverage, dental visit frequency, and for mental health assessment.\n\nAge is divided into six groups: (18-30), (31-40), (41-50), (51-60), and over 60 years. Gender is categorized as either female or male. Race and ethnicity are classified as non-Hispanic White, non-Hispanic Black, Mexican American and other Hispanic, and non-Hispanic Asian. Poverty indices are categorized into low, middle, and high. Marital status is indicated as yes or no. Occupation is categorized as working and non-working. Dental visits are classified as regular and not regular. Dental insurance coverage is delineated as yes or no. Smoking status is divided into never, former, and current smokers. Alcohol consumption is classified as alcohol drinker and non-alcohol drinker.\n\nBy meticulously examining and accounting for these covariates, our objective is to obtain results that reflect the true relationship between the exposure and outcome, minimizing the confounding effects of other variables.\n\nThe data were derived by consolidating information from demographic records, health questionnaires, clinical examinations, and limited access data sourced from NHANES (2011–2012) and corresponding files from NHANES (2013–2014). To ensure unbiased point estimates and accurate variance estimation, given the complex sampling design of NHANES, appropriate sampling weights were applied. SAS version 9.4, survey procedures were utilized, following the guidelines set by the National Center for Health Statistics and the Centers for Disease Control and Prevention.\n\nTo analyze the demographics and disease status of the study population, the Rao-Scott chi-squared test was employed, taking into consideration the survey design complexities. Additionally, a logistic regression model was utilized to assess the influence of mental health on periodontal disease. The significance level was established at p ≤ 0.05, ensuring a stringent evaluation of the relationships within the study. These methodological approaches contribute to the robustness and reliability of our findings.\n\n\nResults\n\nThe demographic characteristics of the study subjects are presented in Table 1, with weighted percentages. Among the 2764 subjects, more than a quarter (29.1%) were aged over 60 years, 52% were females, 42.1% identified as non-Hispanic white, 38.7% reported a high household level, and over half (54.1%) held either an associate or college degree. A majority of subjects had some form of health insurance, and the majority had visited the dentist within the 12 months preceding the survey.\n\na Weighted row percentages.\n\nThe subjects were categorized based on the severity of periodontitis, as outlined in Tables 2 and 3, distinguishing between no, mild, moderate, and severe cases. Significant differences in the prevalence of periodontitis were observed based on subjects' education levels. However, no significant differences were noted in the prevalence of periodontitis based on the subjects' mental health. Notably, the prevalence of periodontitis varied significantly according to subjects' marital status, with approximately 6.6% of married subjects and 10.8% of unmarried subjects experiencing some form of periodontitis. A statistically significant association was found.\n\na Weighted row percentages.\n\n* By Rao-Scott chi-square test.\n\na Weighted row percentages.\n\nUnadjusted odds ratios (OR) were computed through logistic regression, controlling for all confounders, and are presented with a 95% confidence interval (CI) in Table 4. The logistic regression analysis indicated that the odds of periodontal disease were higher among those who reported feeling bad about themselves for more than half of the day compared to those who reported not feeling that way at all (OR 1.170, 95% CI 0.533-2.474). However, this association was not statistically significant (p>0.05).\n\n\nDiscussion\n\nThe primary objective of this study was to examine the relationship between mental health (self-perception) and periodontal disease. The study findings revealed no discernible difference in the prevalence of periodontitis between individuals with mental health issues and those without. However, it is noteworthy that the odds of periodontal disease were somewhat higher among those who reported feeling bad about themselves for more than half of the day, though this difference did not reach statistical significance. Additionally, male participants exhibited a higher likelihood of periodontal disease compared to female participants. Furthermore, lacking insurance coverage was significantly associated with the prevalence of periodontitis.\n\nThe study findings presented here cannot be directly compared with other studies to date due to variations in the measures used to assess stress and psychosocial conditions. Nevertheless, common factors across these studies include stress as a factor and the outcome variable, which is periodontal disease.\n\nMonteiro da Silva et al. (1998) found no significant difference between psychosocial stress and periodontal disease.27 Similarly, Solis et al. (2004) reported no association between depression, hopelessness, psychiatric symptoms, and established or severe periodontitis.28 Castro et al. (2006) also concluded that there was no significant association between periodontitis and the analyzed psychosocial factors.29 The present study aligns with the findings of Shende et al. (2016), where the oral hygiene and periodontal status of individuals with mild anxiety and depression were not different from those without anxiety and depression.30 Thus, this study does not demonstrate stress as a causative factor for periodontal disease, despite observing a difference in the periodontal status of individuals with or without normal mental health, which was not statistically significant.\n\nThe current study's results are consistent with Genco et al.'s (1998) findings, indicating that various measures of stress, including life events and daily strains, were not correlated with periodontal disease. Only financial strain showed a significant association with greater attachment loss and alveolar bone loss after adjusting for variables such as age and smoking. Subjects with higher financial strain and those with depression had a significantly higher risk for periodontal disease.11\n\nOne intriguing observation in the present study was the lower prevalence of periodontal disease and related findings in individuals with dental insurance compared to those without insurance. The possession of dental insurance appears to contribute to a sense of mental well-being, potentially reducing financial-related stress and mitigating the negative impact on periodontal disease. This aligns with the findings of Genco et al. (1998), who demonstrated a correlation between financial strain and poor periodontal health.11 Similarly, a study exploring the relationship between mental health and oral health in older individuals in Australia highlighted that the availability of free treatment or provision of dental insurance offers a sense of comfort in daily life, potentially shielding against mental health issues.31 Ng and Leung (2006) also support this perspective, suggesting that individuals with higher mean clinical attachment level values tended to have higher scores on job and financial strain scales compared to periodontally healthy individuals.32\n\nThe findings of the present study diverge from those reported by Mahendra et al. (2011), Reshma et al. (2013), Vyas et al. (2018), and various other animal and human studies.23,24,33 These studies employed diverse stress measures, including cortisol levels and other stress assessment methods. Discrepancies between the present study's findings and those of the aforementioned studies could arise from differences in methodology, the type of assessment employed, considered co-variables, and the demographic characteristics of the study participants. Many studies focused on specific groups exposed to stress, such as police personnel or older individuals, whereas our study encompassed a broader sample, considering individuals from various backgrounds in relation to mental health. The diverse nature of the study population may contribute to the variations observed in the results.\n\nThe current investigation has notable strengths, including its reliance on data from a large-scale population-based survey with a robust sampling and weighting system. This survey encompassed a diverse range of participants, including both females and males, various age groups, individuals with different socioeconomic statuses, and those with and without insurance. The inclusion of these variables, which are not often considered collectively in previous studies, enhances the reliability of the associations found within this research. However, there are limitations to consider. Firstly, mental health status was assessed based on self-reported answers from the participants, which may introduce subjectivity and potential bias into the study outcomes. The broad and complex nature of assessing mental health on a single-point measure or limited parameters may not fully capture the true mental health status of individuals. Additionally, the cross-sectional design of the study limits the ability to infer causality in the observed associations. The study does not confirm the outcome, and the link between stress-associated odds of periodontal disease and behavioral or pathophysiological changes remains to be determined.\n\nMoreover, the study acknowledges the potential bidirectional relationship between oral health concerns and mental health status. For instance, the appearance of teeth, mouth, or dentures, as well as problems with them, might impact social interaction, potentially contributing to mental health issues such as feelings of hopelessness and depression. Controlling for these variables in a study investigating the relationship between mental health status and periodontal disease becomes challenging, and the true measured outcome may be affected.\n\nTo enhance future research, prospective studies with a focus on biochemical and physiological mechanisms by which psychosocial stress contributes to periodontal destruction are needed. These studies could establish the biological rationale for the observed relationship. Furthermore, refining the definition of stress and employing a standardized protocol to assess stress and associated factors would contribute to clearer comparisons of periodontal status among individuals.\n\n\nConclusion\n\nIn conclusion, within the constraints of this study, it can be deduced that there is no statistically significant difference in the periodontal status between individuals with compromised mental health and those without such issues. The findings suggest that mental health, as assessed through self-reported responses, may not be a robust predictor of periodontal disease in the studied population. Despite observing higher odds of periodontal disease among individuals who reported feeling bad about themselves for more than half of the day, this difference did not reach statistical significance.\n\n\nEthics and consent\n\nThe protocols for collecting oral health data in the NHANES 2011–2012 and NHANES 2013–2014 cycles received approval from the Centers for Disease Control and Prevention National Center for Health Statistics Research Ethics Review Board. All survey participants provided written informed consent before publishing their information. https://www.cdc.gov/nchs/nhanes/irba98.htm",
"appendix": "Data availability\n\nAljoghaiman, Eman (2024). The Relationship Between Mental Health and Periodontal Disease: Insights from NHANES Data. figshare. Dataset. https://doi.org/10.6084/m9.figshare.25662735 34\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nSlots J: Periodontology: past, present, perspectives. Periodontol. 2013; 62(1): 7–19. PubMed Abstract | Publisher Full Text\n\nSchätzle M, Löe H, Bürgin W, et al.: Clinical course of chronic periodontitis. I. Role of gingivitis. J. Clin. Periodontol. 2003; 30(10): 887–901. Publisher Full Text\n\nNomura Y, Morozumi T, Nakagawa T, et al.: Site-level progression of periodontal disease during a follow-up period. PLoS One. 2017; 12(12): e0188670. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHajishengallis G, Chavakis T: Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat. Rev. Immunol. 2021; 21(7): 426–440. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHajishengallis G, Chavakis T, Lambris JD: Current understanding of periodontal disease pathogenesis and targets for host-modulation therapy. Periodontol. 2020; 84(1): 14–34. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhang J, Lin S, Luo L, et al.: Psychological stress: neuroimmune roles in periodontal disease. Odontology. 2023; 111(3): 554–564. PubMed Abstract | Publisher Full Text\n\nKrishnan V, Nestler EJ: The molecular neurobiology of depression. Nature. 2008; 455(7215): 894–902. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWarren KR, Postolache TT, Groer ME, et al.: Role of chronic stress and depression in periodontal diseases. Periodontol. 2014; 64(1): 127–138. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGundala R, Chava V, Reddy R: Role of stress in periodontal disease. Indian J Dent Adv. 2012; 4(1): 763–771.\n\nReed RG, Raison CL: Stress and the immune system. Environmental influences on the immune system. 2016; pp.97–126. Publisher Full Text\n\nGenco RJ, Ho AW, Kopman J, et al.: Models to evaluate the role of stress in periodontal disease. Ann. Periodontol. 1998; 3(1): 288–302. Publisher Full Text\n\nPitzurra L, Loos BG: Stress and periodontitis. Ned. Tijdschr. Tandheelkd. 2020; 127(6): 358–364. Publisher Full Text\n\nParwani R, Parwani SR: Does stress predispose to periodontal disease? Dent. Update. 2014; 41(3): 260–272. 7-8, 71-2. PubMed Abstract | Publisher Full Text\n\nGunepin M, Derache F, Trousselard M, et al.: Impact of chronic stress on periodontal health. J. Oral. Med. Oral Surg. 2018; 24(1): 44–50. Publisher Full Text\n\nLopez R, Fernandez O, Jara G, et al.: Epidemiology of necrotizing ulcerative gingival lesions in adolescents. J. Periodontal Res. 2002; 37(6): 439–444. PubMed Abstract | Publisher Full Text\n\nRosania AE, Low KG, McCormick CM, et al.: Stress, depression, cortisol, and periodontal disease. J. Periodontol. 2009; 80(2): 260–266. PubMed Abstract | Publisher Full Text\n\nSedghi LM, Bacino M, Kapila YL: Periodontal Disease: The Good, The Bad, and The Unknown. Front. Cell. Infect. Microbiol. 2021; 11: 766944. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMarcenes WS, Sheiham A: The relationship between work stress and oral health status. Soc. Sci. Med. 1992; 35(12): 1511–1520. Publisher Full Text\n\nLocker D, Leake JL: Risk indicators and risk markers for periodontal disease experience in older adults living independently in Ontario, Canada. J. Dent. Res. 1993; 72(1): 9–17. PubMed Abstract | Publisher Full Text\n\nCroucher R, Marcenes WS, Torres MC, et al.: The relationship between life-events and periodontitis. A case-control study. J. Clin. Periodontol. 1997; 24(1): 39–43. PubMed Abstract | Publisher Full Text\n\nGenco RJ, Ho AW, Grossi SG, et al.: Relationship of stress, distress and inadequate coping behaviors to periodontal disease. J. Periodontol. 1999; 70(7): 711–723. PubMed Abstract | Publisher Full Text\n\nWimmer G, Janda M, Wieselmann-Penkner K, et al.: Coping with stress: its influence on periodontal disease. J. Periodontol. 2002; 73(11): 1343–1351. PubMed Abstract | Publisher Full Text\n\nMahendra L, Mahendra J, Austin RD, et al.: Stress as an aggravating factor for periodontal diseases. J. Clin. Diagn. Res. 2011; 5: 889–893.\n\nVyas M: Study on Correlation of Stress and Periodontal Status. JAMDSR. 2018; 6(7): 76–78.\n\nAljoghaiman E, Helmi H: Do more pregnancies increase the risk of periodontal disease?2023.\n\nEke PI, Page RC, Wei L, et al.: Update of the case definitions for population-based surveillance of periodontitis. J. Periodontol. 2012; 83(12): 1449–1454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMonteiro da Silva AM, Newman HN, Oakley DA, et al.: Psychosocial factors, dental plaque levels and smoking in periodontitis patients. J. Clin. Periodontol. 1998; 25(6): 517–523. PubMed Abstract | Publisher Full Text\n\nSolis AC, Lotufo RF, Pannuti CM, et al.: Association of periodontal disease to anxiety and depression symptoms, and psychosocial stress factors. J. Clin. Periodontol. 2004; 31(8): 633–638. PubMed Abstract | Publisher Full Text\n\nCastro GD, Oppermann RV, Haas AN, et al.: Association between psychosocial factors and periodontitis: a case-control study. J. Clin. Periodontol. 2006; 33(2): 109–114. Publisher Full Text\n\nShende AS, Bhatsange AG, Waghmare AS, et al.: Determining the association between stress and periodontal disease: A pilot study. J Int Clin Dent Res Organ. 2016; 8(2): 111–114. Publisher Full Text\n\nChiva A, Stears D: Promoting the health of older people: The next step in health generation. Citeseer; 2001.\n\nNg S, Leung W: Association between dental anxiety and periodontal attachment loss. J. Dent. Res. 2006.\n\nReshma AP, Arunachalam R, Pillai JK, et al.: Chromogranin A: Novel biomarker between periodontal disease and psychosocial stress. J. Indian Soc. Periodontol. 2013; 17(2): 214–218. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAljoghaiman E: The Relationship Between Mental Health and Periodontal Disease: Insights from NHANES Data. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "306426",
"date": "13 Aug 2024",
"name": "Morenike Folayan",
"expertise": [
"Reviewer Expertise epidemiology and oral health"
],
"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 Relationship Between Mental Health and Periodontal Disease: Insights from NHANES Data\nThanks for this very important study generated from a secondary analysis of a large database. Please find below suggestions to strengthen the manuscript Abstract\nPlease include clearly that this was a secondary data analysis of the NHANEs data Include information on the period the data was collected Please provide details on the covariate variables extracted What kind of analysis was conducted with the Rao-Scott chi-squared test. Please avoid making readers assume what was done. What demographic variables were included in the analysis What disease status is been referred too? How was mental health measured for this study? What is the sample size for this study? This information should be included in the result section For the report, please report the descriptive variables before the inferential analysis reports. Authors noted a significant difference in periodontal status by marital status and by health insurance status but there is no report on the CI or the p value of these observations. There is also no clarity about how the results of these tests of associations answer the study objectives as the objective had Mental health as the dependent variable. Is ‘feeling bad about themselves for more than half of the day’ the measure of mental health for this study? The conclusion that ‘The findings underscore potential associations between mental health, marital status, and access to health insurance with periodontal disease’ is not valid based on this study results.\nINTRODUCTION\nA comprehensive introduction The introduction is missing on the conceptual framework that suggest that first suggests that self-perception is a mental health issue, and that there are suggestive links between self-perception (about what) and periodontal diseases. Please address this concisely in the introduction.\nMETHODs\nPlease provide explicit details on how mental health was measured. Please be explicit about the periodontal index used for this study. I think what is listed as covariates are defined as confounders. These needs to be clarified please. What informed the age categorisation? There is no justification for the age categorisation nor is the interpretation and application of the findings meaningful based on this age categorisation. Secondly, since this data is large and likely not be skewed, it is best to treat age as a continuous variable. Please how were these variables measured - education, socioeconomic status, poverty/income ratio, marital status, BMI, HbA1C, dental insurance coverage, dental visit frequency, and mental health assessment Please how was the data on poverty indices collected before being categorized into low, middle, and high? Please did the authors check for collinearity between the variables such as education, socioeconomic status, poverty/income ratio? This statement is not clear: ‘To analyze the demographics and disease status of the study population, the Rao-Scott chi-squared test was employed, taking into consideration the survey design complexities’. The Rao-Scott chi-squared test is a test of association. Not sure how this can be an analytic tool for ‘the demographics and disease status of the study population’ The authors wrote - ‘Additionally, a logistic regression model was utilized to assess the influence of mental health on periodontal disease’. This was a cross sectional study and so the data cannot give information on influence. All it can suggest are risk indicators based on the results of the associations.\nResults\nPlease for the results, write the figures and the percentage in brackets Please do not round up the figures to report a quarter etc. Please be precise with the results. You can round up in the discussion. Please can you report the study participants as participants rather than subjects The asterisks in the Table 2 suggests that Rao-Scott chi-square test as not applied to all variables Table 2 also suggests that the variables listed in the methodology were treated as co-variates and not confounders. Please be clear with your methodology and the use of terminologies. The test of association cannot measure effect. Please the title to the section is misleading Please in the narrative on tables 2 and 3, please include information on the determinants of the report of significant associations Please be specific on the percentage and type of periodontal disease referred too. The table did not report on ‘some forms’ of periodontal diseases Table 4 is not clear – what were the confounding variables adjusted for in this table.\nIn view of the non-clarity of the methodology and results, I am unable to review the discussion until this is clarified. The authors are encouraged to use the TROBE guidelines to guide the review and the structuring of the paper.\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?\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? Partly",
"responses": [
{
"c_id": "12600",
"date": "08 Nov 2024",
"name": "Eman AlJoghaiman",
"role": "Author Response",
"response": "Dear Reviewer, We would like to express our sincere gratitude for your insightful review and valuable suggestions regarding our manuscript. We have carefully revised the manuscript and provided detailed responses below to your comments one by one. Please let us know if you have any further questions. Thank you for your time. Reviewer 1: Thanks for this very important study generated from a secondary analysis of a large database. Please find below suggestions to strengthen the manuscript. Comment: Abstract: Please include clearly that this was a secondary data analysis of the NHANEs data -Response: Added Comment: Include information on the period the data was collected -Response: Added Comment: Please provide details on the covariate variables extracted -Response: Added Comment: What kind of analysis was conducted with the Rao-Scott chi-squared test. Please avoid making readers assume what was done. -Response: It is a chi-square test used for association. Thank you Comment: What demographic variables were included in the analysis -Response: All demographic variables included are present in the material method section below because listing them here will be difficult because of word limitation for abstract. Comment: What disease status is been referred too? -Response: Periodontal disease Comment: How was mental health measured for this study? -Response: Added in the material method section Comment: What is the sample size for this study? This information should be included in the result section -Response: Added Comment: For the report, please report the descriptive variables before the inferential analysis reports. -Response: Corrected Comment: Authors noted a significant difference in periodontal status by marital status and by health insurance status but there is no report on the CI or the p value of these observations. There is also no clarity about how the results of these tests of associations answer the study objectives as the objective had Mental health as the dependent variable. -Response: Periodontal status is the dependent variable, and details are added in the result section. Thank you Is ‘feeling bad about themselves for more than half of the day’ the measure of mental health for this study? -Response: Yes Comment: The conclusion that ‘The findings underscore potential associations between mental health, marital status, and access to health insurance with periodontal disease’ is not valid based on this study results. -Response: Our findings suggest trends in periodontal disease prevalence linked to mental health, marital status, and access to health insurance. However, the absence of statistically significant findings calls for caution in interpreting these relationships. We recommend that future studies further investigate these potential associations to provide a clearer understanding INTRODUCTION Comment: A comprehensive introduction -Response: Modified. Thank you Comment: The introduction is missing on the conceptual framework that suggest that first suggests that self-perception is a mental health issue, and that there are suggestive links between self-perception (about what) and periodontal diseases. Please address this concisely in the introduction. -Response: Based on the reviewer’s comment regarding the The introduction is missing on the conceptual framework authors have revise the introduction. Thank you METHOD Comment: Please provide explicit details on how mental health was measured. -Response: Added Comment: Please be explicit about the periodontal index used for this study. -Response: Added Comment: I think what is listed as covariates are defined as confounders. These needs to be clarified please. -Response: We listed them as covariates…. Comment: What informed the age categorisation? There is no justification for the age categorisation nor is the interpretation and application of the findings meaningful based on this age categorisation. Secondly, since this data is large and likely not be skewed, it is best to treat age as a continuous variable. -Response: Age categorization was done to check the variability in the different age groups. Comment: Please how were these variables measured - education, socioeconomic status, poverty/income ratio, marital status, BMI, HbA1C, dental insurance coverage, dental visit frequency, and mental health assessment -Response: Thank you for the comment, authors have listed all categories about the measurements in table 1. Comment: Please how was the data on poverty indices collected before being categorized into low, middle, and high? -Response: Based on the poverty income ratios, categories were created to represent different socioeconomic status groups. Here's a common approach: Below Poverty Line: Participants with a poverty income ratio less than 1.0 are considered below the poverty line. Near Poverty: Participants with a poverty income ratio between 1.0 and 1.25 are often categorized as near-poverty. Low-Income: Participants with a poverty income ratio between 1.25 and 2.0 are typically categorized as low-income. Middle-Income: Participants with a poverty income ratio between 2.0 and 3.0 are considered middle-income. High-Income: Participants with a poverty income ratio greater than 3.0 are categorized as high-income. Comment: Please did the authors check for collinearity between the variables such as education, socioeconomic status, poverty/income ratio? -Response: The authors appreciate your feedback and will consider using collinearity diagnostics in future studies to improve the rigor of our findings. Our investigation focused on ensuring that our regression models were robust and reliable. While we did not directly collect collinearity statistics, we were aware of the possibility of multicollinearity when selecting and incorporating variables in our models. Comment: This statement is not clear: ‘To analyze the demographics and disease status of the study population, the Rao-Scott chi-squared test was employed, taking into consideration the survey design complexities’. The Rao-Scott chi-squared test is a test of association. Not sure how this can be an analytic tool for ‘the demographics and disease status of the study population’ -Response: The lines are Rephrased. Comment: The authors wrote - ‘Additionally, a logistic regression model was utilized to assess the influence of mental health on periodontal disease’. This was a cross-sectional study and so the data cannot give information on influence. All it can suggest are risk indicators based on the results of the associations. -Response: Thank you for your suggestion. Results Comment: Please for the results, write the figures and the percentage in brackets -Response: Done Comment: Please do not round up the figures to report a quarter etc. Please be precise with the results. You can round up in the discussion. -Response: Thank you Comment: Please can you report the study participants as participants rather than subjects -Response: Done, Thank You Comment: The asterisks in the Table 2 suggests that Rao-Scott chi-square test as not applied to all variables -Response: Corrected, Thank you Comment: Table 2 also suggests that the variables listed in the methodology were treated as co-variates and not confounders. Please be clear with your methodology and the use of terminologies. -Response: Corrected Comment: The test of association cannot measure effect. Please the title to the section is misleading -Response: Corrected Comment: Please in the narrative on tables 2 and 3, please include information on the determinants of the report of significant associations -Response: Corrected Comment: Please be specific on the percentage and type of periodontal disease referred too. The table did not report on ‘some forms’ of periodontal diseases -Response: Corrected Comment: Table 4 is not clear – what were the confounding variables adjusted for in this table. -Response: All demographical characteristics. Comment: In view of the non-clarity of the methodology and results, I am unable to review the discussion until this is clarified. The authors are encouraged to use the TROBE guidelines to guide the review and the structuring of the paper. -Response: Thank you for your valuable review"
}
]
},
{
"id": "317918",
"date": "16 Sep 2024",
"name": "Junaid Ahmed",
"expertise": [
"Reviewer Expertise Forensic Odontology",
"TMJ disorders",
"Oral Cancer",
"3D 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\n1.The inclusion & exclusion criteria needs to be listed more elaborately 2.The authors have not mentioned their source of demographic data including the country from where the data is sourced. 3..Was the NHANES data previously published by the government?.The authors need to clarify. 4.Have the authors taken the necessary permission to publish the data from the competent sources? 5.The study setting in which the objectives of the present research is mentioned is not clear in the manuscript. 6.The authors need to mention the sample size of the data and whether any methodology was utilized for sample size estimation. 7.The self reported mental health status is a big limitation in the present study and any direct relationship between mental health & periodontal disease cannot be inferred from the present study. 8.Quality of written english needs to be improved and a few incoherent sentences needs to be rephrased. 9.A few comments have been highlighted in the attached manuscript\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12598",
"date": "08 Nov 2024",
"name": "Eman AlJoghaiman",
"role": "Author Response",
"response": "Dear Reviewer, We would like to express our sincere gratitude for your insightful review and valuable suggestions regarding our manuscript. We have carefully revised the manuscript and provided detailed responses to your comments, which are included alongside the revised version. Thank you very much for your time and consideration. Dr. Eman"
},
{
"c_id": "12601",
"date": "08 Nov 2024",
"name": "Eman AlJoghaiman",
"role": "Author Response",
"response": "Dear Reviewer, We would like to express our sincere gratitude for your insightful review and valuable suggestions regarding our manuscript. We have carefully revised the manuscript and provided detailed responses below to your comments one by one. Please let us know if you have any further questions. Thank you for your time. Reviewer comment 1: The inclusion & exclusion criteria needs to be listed more elaborately Author response: Added in the attached manuscript. Thank you Reviewer comment 2: The authors have not mentioned their source of demographic data including the country from where the data is sourced. Author response: The National Health and Nutrition Examination Survey (NHANES) is a comprehensive cross-sectional survey conducted in the United States, designed to offer a nationally representative overview of non-institutionalized individuals residing in households. Reviewer comment 3: Was the NHANES data previously published by the government?. The authors need to clarify. Author response: Yes, it is published and publicly available for other to re-use the data. The source of the data is provided in the method section. Thank you Reviewer comment 4: Have the authors taken the necessary permission to publish the data from the competent sources? Author response: Yes, the data is available freely. Thank you Reviewer comment 5: The study setting in which the objective of the present research is mentioned is not clear in the manuscript. Author response: Can you please specify what exactly should be added? Reviewer comment 6: The authors need to mention the sample size of the data and whether any methodology was utilized for sample size estimation. Author response: No sample size was calculated because authors utilized whole data available in the website. Thank you Reviewer comment 7: The self reported mental health status is a big limitation in the present study and any direct relationship between mental health & periodontal disease cannot be inferred from the present study. Author response: Noted thank you Reviewer comment 8: Quality of written English needs to be improved and a few incoherent sentences needs to be rephrased. Author response: Thank you for the comment, we have done English proofread and rephrased the sentences for more readability. Reviewer comment 9: A few comments have been highlighted in the attached manuscript Author response: Thank you for the comments."
}
]
}
] | 1
|
https://f1000research.com/articles/13-709
|
https://f1000research.com/articles/13-359/v1
|
23 Apr 24
|
{
"type": "Review",
"title": "Holistic approaches to living well with endometriosis",
"authors": [
"Jessica Desai",
"Sophie Strong",
"Elizabeth Ball",
"Jessica Desai",
"Elizabeth Ball"
],
"abstract": "Endometriosis is a common chronic condition for which there is currently no cure. Those suffering from endometriosis-related pelvic pain (ERPP) may struggle with side effects and/or risks presented by conventional medical and surgical treatment strategies, or not get pain relief. Increasing numbers of endometriosis patients wish to explore holistic management with fewer side effects, however it is important that medical professionals maintain an evidence-based practice for recommended treatments. We present up-to-date evidence of holistic strategies used for managing ERPP including nutritional strategies, body and mind therapies, acupuncture, traditional Chinese medicine (TCM) and the use of adjunct devices such as phallus length reducers and transcutaneous electrical nerve stimulation (TENS).\nRecent findings\nNutrition: Gluten-free, low-nickel and high intake of omega-3 polyunsaturated fatty acids diets improve ERPP. Low FODMAP (fermentable oligo-, di-, monosaccharides and polyols) is helpful in those with concurrent irritable bowel syndrome. Body and mind: Cognitive behaviour therapy (CBT) is particularly beneficial in postoperative pain reduction, whilst mindfulness has been shown to reduce pain scores and dyschezia. Progressive muscle relaxation therapy and regular yoga sessions improve ERPP and Quality of life.\nAcupuncture: 15 randomised control trials assessing acupuncture and moxibustion show improved pain scores when compared to those receiving conventional therapies alone. Adjunct devices: TENS improves deep dyspareunia and lessens the number of days pain is experienced.\n\nConclusions Holistic management strategies for ERPP should be incorporated into routine counselling when discussing conservative, medical and or surgical treatments for endometriosis. The growing evidence presented for the use of holistic management strategies gives hope to those patients who cannot have, or don’t respond to conventional approaches and as an adjunct alongside standard treatments.",
"keywords": [
"Endometriosis",
"holistic treatment for endometriosis",
"complementary treatment for endometriosis",
"chronic pelvic pain"
],
"content": "Introduction\n\nEndometriosis, an inflammatory women’s health condition affecting about 10% of the female population,1 can cause infertility and chronic pelvic pain (CPP) with acute flares. Pain centralisation is thought to play a role for many patients.2 The mainstay of treatment has been laparoscopic excision or ablation of implants/affected organs. Hormonal or non-hormonal medical therapies can replace or complement this, along with pain relief.\n\nHowever, in our experience at a busy tertiary endometriosis centre in London, many women with endometriosis-related pelvic pain (ERPP) have adopted holistic approaches to manage pain and improve their quality of life (QOL). Recent developments also call us to reassess and contextualise traditional treatments, to look further afield for more comprehensive approaches, which support patient autonomy and empowerment toward living well with endometriosis.\n\n1. A systematic review (SR) of surgical outcomes for endometriosis3 showed that 11.8% of patients reported no pain improvement. Women with isolated surface endometriosis in particular, may not benefit from surgery,4 which is currently the focus of randomised control trial (RCT) ESPriT2 (NCT04081532).\n\n2. The coronavirus disease 2019 (COVID-19) pandemic transformed how women seek advice on endometriosis. ‘Hormonophobia’ appears to be on the rise on social media platforms, with increasing numbers of women sharing negative experiences of hormonal contraceptives, reducing the willingness to try them.5\n\n3. Antidepressants and Gabapentin, previously prescribed as neuromodulators are not as effective as previously thought.6\n\nIn front of this backdrop and with an understanding that living with chronic conditions can be eased by holistic approaches and self-management,7 we present recent advances in this field.\n\nNumerous SRs support the role of nutrition in managing chronic pain conditions.8,9 Optimising diet quality with a high intake of anti-inflammatory nutrients reduces pain severity by modulating the body’s inflammatory response.10 Gut microbiome dysbiosis in inflammatory pain conditions such as endometriosis is hypothesised to cause incorrect immune responses resulting in pain from central sensitisation pathways. Probiotics and FODMAP diets (omitting fermentable oligo-, di-, monosaccharides and polyols), are beneficial in treating visceral pain.11 More research into dietary effects on endometriosis is recommended,12 as many studies to date have small population sizes with heterogeneity between intervention groups.\n\nA SR (one RCT and five observational studies) of low FODMAP, gluten-free and low-nickel diets as well as high intake of omega-3 polyunsaturated fatty acids (average treatment dose palmitoylethanolamide 400 mg & polydatin 40 mg twice daily for 3 months)13–15 reported that all diets, with the exception of low FODMAP reduced pain.16 Those with concurrent irritable bowel syndrome (IBS) may benefit the most from low-FODMAPs; observational data (n=160) demonstrated symptom improvement compared to patients with IBS alone (72% vs. 40%, respectively, p = 0.001).17\n\nCompared to controls, endometriosis patients may have a higher rate of nickel allergic contact mucositis (odds ratio: 2.474; 95% confidence interval: 1.023~5.988; p = 0.044),18 causing IBS-like symptoms. Reducing nickel-rich foods e.g. tomatoes, whole wheat, and soy, resulted in significant improvement of CPP (p < 0.05) in a prospective 3-month observational study of 31 women with endometriosis and gastrointestinal symptoms.19\n\nKrabbenborg et al.20 observed 157 women with endometriosis assessing which dietary modifications patients had already implemented improved their QOL using the EHP-30 score. The most used diets were the endometriosis diet (self-selecting nutrients to omit thought by the individual to worsen their symptoms), gluten free, low-FODMAP, low-lactose and weight loss diets. Although EHP-30 scores did not significantly alter with dietary modification, pain reduction was noted in 71.3% of patients, with gluten-free showing the greatest impact. Dietary modifications have a greater impact with longer adherence.\n\nIn a placebo-controlled triple-blind RCT (n = 120), garlic extract (400 mg daily over 12 weeks) showed a significant reduction in ERPP (p < 0.05). Purported mechanisms are reduction in oxidative stresses, prostaglandin production, endometriosis cell proliferation and increased oestrogen elimination.21\n\nEndometriosis severity may be associated with both low and high BMI.22 The association between BMI and endometriosis severity might be more complicated than a simple correlation. A confounding factor for both endometriosis and obesity may be systemic inflammation.23\n\nIt is tempting to speculate whether maintenance of a normal BMI is beneficial for symptom control, but studies designed to assess change in weight for ERPP are lacking.\n\nBody & mind therapies\n\nPoor mental health may result secondary to the multifactorial impact endometriosis has on physical, sexual, and psychological well-being.24 Strategies such as cognitive behavioural therapy (CBT), yoga and relaxation techniques can be valuable. Increasing evidence suggests psychosocial factors, such as preoperative pain catastrophising independently impact pain experience, severity of symptoms and recurrence of endometriosis.25,26 Patient awareness and self-uptake of psychological approaches for ERPP are increasingly popular, with 93.8% of women sampled in a cross-sectional survey distributed via The Endometriosis Network Canada (n = 434) utilising at least one psychological management strategy.27\n\nCBT\n\nCBT is recognised as an effective treatment for chronic pain and associated mental health conditions, including CPP.28 Current research interest is evidenced by the publication of three RCT protocols assessing efficacy of CBT29,30 and yoga with CBT31 on QOL of patients with endometriosis. Boersen’s RCT30 aims to recruit 100 patients undergoing endometriosis surgery, assessing benefits of CBT in postoperative care.\n\nWu et al.32 assessed the benefits of CBT plus usual care compared to usual care alone in post-surgical endometriosis patients with a case-control study (Intervention group n = 48, Control group n = 48), utilising one CBT session before and six sessions post-surgery. During a 6-month follow-up, participants provided a score on the depression, anxiety, and stress (DASS-21). Anxiety scores improved significantly (p = 0.0091).\n\nAuthors suggest patient education played a large role in self-management of ERPP following CBT.\n\nMindfulness\n\nMindfulness is a psychological technique that draws on awareness and non-judgemental acceptance of present personal experience. The mindfulness-based stress reduction (MBSR) programme, was first developed by Kabat-Zinn33 as an adjunct to treatment for chronic pain, through relating physical and psychological conditions.\n\nMoreira et al.34 performed an RCT to assess the impact of mindfulness on CPP. They adapted the MBSR programme, forming a brief mindfulness-based intervention (bMBI, n = 31, usual care controls n = 32) which had a reduced intensity and reduced duration (4-weeks instead of 8-weeks). Formal meditation was practised around the theme of ‘reconceptualising pain.’ The intervention group showed reduced pain scores & unpleasantness and dyschezia.\n\nHansen et al.35 found that psychological intervention, with a mindfulness focus, did not reduce perception of pain, but did improve QOL in a three-armed RCT. Participants were randomised to three groups: mindfulness and acceptance-based intervention (n = 20), non-specific psychological intervention that did not include mindfulness (relaxation and guided physical therapy) (n = 19), or a waitlist control that included usual treatment (n = 19). All participants received usual treatment which included analgesia. The ten-week programme developed (MY-ENDO), combined Kabat-Zinn’s MBSR programme and acceptance with commitment therapy. There was no statistically significant reduction in ERPP between the MY-ENDO group and non-specific intervention group (p = 0.144, d = 0.59). Psychological intervention significantly improved QOL-subscales ‘control and powerlessness’ (p = 0.019, d = 0.78), ‘emotional well-being’ (p = 0.003, d = 1.01), and ‘social support’ (p = 0.042, d = 0.66).\n\nQOL was improved through the positive effects on bowel symptoms, specifically diarrhoea (P = 0.035, d = 0.25), within the two intervention groups, thought to be due to physical activity undertaken.\n\nFurther studies are needed to determine whether psychological interventions in general improves QOL or whether there is a need for a mindfulness aspect to the intervention.\n\nYoga\n\nYoga has a long tradition in managing chronic pain. In an AB-design pilot study of 42 women by Ravins et al.,36 participants underwent eight-weeks of conventional therapy followed by eight-weeks of 90-minute endometriosis yoga sessions, bi-weekly. EHP-30 scores and numerical pain rating scale were lower following the completion of the yoga sessions (p = 0.001).\n\nGonçalves’ RCT37 randomly allocated 40 women; an intervention group who practised 90-minutes of yoga bi-weekly for 8 weeks (n = 28) and a control group who did not practise yoga (n = 12). Daily pain was significantly lower among the intervention group (p = 0.0007). EHP-30 domains were assessed at the time of presentation and again at 8-week follow up; pain (p = 0.0046), well-being (p = 0.0009), and image (p = 0.0087) from the central questionnaire, and work (p = 0.0027) and treatment (p = 0.0245) from the modular questionnaire were significantly different. One limitation of this study was the high loss to follow up, with only 57% of participants in the intervention group completing the full yoga-programme, highlighting the challenges faced of adhering to regular yoga practice.\n\nSimilar findings were echoed by Saxena et al.38 in a randomised case-control study of 60 women with CPP. The intervention group (n = 30) who received yoga therapy with conventional therapy (non-steroidal anti-inflammatory drugs, NSAIDs) were compared with the control group (n = 30) who received NSAIDs alone. Pain scores through VAS score and QOL by the World Health Organization quality of life-BREF (WHOQOL-BREF) questionnaire were assessed at the start of the study and again at an 8-week follow up. The yoga-practising group showed a significant decrease in pain intensity (p < 0.001) and improvement in the QOL with a significant increase (p < 0.001) in physical, psychological, social, and environmental domain scores of WHOQOL-BREF.\n\nEnriched environments (consisting of enlarged space, increased physical activity and social interactions) suppresses the development of endometriosis in mice through attenuated adrenergic signalling, enhanced autophagy, and reduced leptin levels.39 Extrapolating this to humans, offering group outdoor physical activities such yoga to optimise environmental enrichment showed significantly less ERPP and perceived stress, improved mood and emotional wellbeing QOL compared with control participants in a recent RCT by Flores.40\n\nProgressive muscle relaxation (PMR)\n\nPMR improved anxiety and depression (p < 0.05), and health-related QOL (p < 0.05) for patients with endometriosis in a study of 100 women receiving Gonadotrophin-releasing hormone (GnRH) agonist treatment. Participants were randomly assigned either to a control group or PMR group, who received 12 weeks of PMR training.41\n\nPsychological and physical interventions positively impact on QOL in patients with ERPP. However, there remains a lack of high-powered trials in mind and body therapies. Consideration must be taken for the barriers to accessing psychological interventions. Patients should not feel their pain is less validated if a physiological approach is offered. Smart-phone applications are nowadays suggested to simplify access to Mindfulness. However, those approaches require co-development with stakeholders to be acceptable and used regularly.42\n\nPelvic floor muscle physiotherapy\n\nPelvic floor muscle dysfunction (specifically levator ani hypertonia and incomplete relaxation) contributes to ERPP with deep infiltrative endometriosis (DIE).43–45\n\nPelvic floor physiotherapy (PFP), with 3D/4D trans-perineal ultrasound, increased levator hiatus area (LHA) which in turn improved dyspareunia and pelvic floor muscle relaxation (PFMR) reduced ERPP. Following a successful pilot study,46 Forno et al. used trans-perineal ultrasound to assess LHA before and after PFP in an RCT of 34 women.47 Participants were assigned to a no intervention group (n = 17), or the treatment group which involved five PFP sessions (n = 17). Physiotherapy sessions involved the Thiele massage, using digital pressure to elongate and relax muscles, restoring normal tone. PFMR improved on maximum Valsalva manoeuvre in the intervention group compared to the control (20.0 ± 24.8% vs –0.5 ± 3.3%, respectively; p = 0.02), and superficial dyspareunia pain scores reduced (p < 0.01).\n\nPrevious studies have shown acupuncture to be a suitable tool in reducing ERPP, and is considered a safe therapy with minimal side effects.48,49 Several recent case studies have shown symptomatic improvement with acupuncture.50,51 Yan et al. published a protocol for SR and meta-analysis of RCTs on acupuncture benefits for endometriosis symptoms. ESHRE guidelines52 acknowledge that acupuncture may be a beneficial tool, however the studies that were available at that time were limited and not free from bias.\n\nWang et al.53 recently published a systematic review of 15 RCTs (sample sizes between 10 and 54), which assessed the effectiveness of acupuncture and/or moxibustion for the treatment of endometriosis. Compared with sham acupuncture, actual acupuncture was more effective at reducing dysmenorrhoea VAS pain score (mean difference [MD] − 2.40, 95% CI [− 2.80, − 2.00]; moderate certainty evidence), pelvic pain VAS score (MD − 2.65, 95% CI [− 3.40, − 1.90]; high certainty evidence) and dyspareunia VAS scores (MD − 2.88, [− 3.83, − 1.93]), lessened the size of ovarian cyst (MD − 3.88, 95% CI [− 7.06, − 0.70]), and improved QOL. These promising results suggest that acupuncture is an effective adjunct to treating ERPP.\n\nIn a multicentre, randomised, single-blind, placebo-controlled trial54 assessing the effects of acupuncture on endometriosis related symptoms (n = 106), acupuncture was delivered to the intervention group (n = 51) as 30-minute sessions once daily, three times a week, starting one week before expected onset of menstruation, for a total duration of 12-weeks. The control group (n = 53) received sham acupuncture. Lower VAS scores were seen in the intervention group at 12 weeks for dysmenorrhoea (-2.82 (-3.47, -2.18) and QOL, (EHPscore) -18.88 (-31.88, -5.87)), but not for pelvic pain and dyspareunia. At 24 weeks no statistical benefits were seen, suggesting acupuncture is a suitable immediate therapy for endometriosis related dysmenorrhoea, however the effects of acupuncture may not be sustainable over a long period of time and repeated therapy would be necessary.\n\nPhallus length reducing devices\n\nThe Ohnut© device is a phallus length reducer worn over the penis or penetrating object with the intention to reduce endometriosis-associated deep dyspareunia. The effectiveness of this device is currently being assessed in a pilot RCT of 40 participants by Zhang55 who will be randomised into an intervention group or a waitlist control group.\n\nTranscutaneous electrical nerve stimulation (TENS)\n\nA TENS unit passes a current through electrodes placed on the skin for targeted pain relief via the gate control theory.56 Its use has been shown to reduce pain in primary dysmenorrhoea57 and CPP.58,59\n\nMira et al.60 conducted a multicentre RCT of 101 participants with DIE. The study aimed to identify whether the addition of a TENS unit to hormonal therapy (intervention group; n = 53) would provide a greater therapeutic benefit than hormonal treatment alone (control group; n = 48). The TENS device was used twice a day, 20 minutes per day, for 8 weeks. CPP improved in the intervention group (VAS decreased from 7.11 ± 2.40–4.55 ± 3.08, p < 0.001, 36% decrease), whereas it did not in the control group (VAS from 7.33 ± 2.09–7.06 ± 2.33, p = 0.554, 3.68% decrease). A greater improvement in deep dyspareunia was found in the intervention group, 32.67% reduction vs. 13.84% reduction in the control group. There was a decrease in the number of days participants experienced pain from the first week to the eighth week (from 3.27 to 2.22, p = 0.028, 32.11% decrease), which was not identified in the control group (from 4.55 to 4.07, p = 0.203, 10.54% decrease). This study was conducted over a relatively short time interval, therefore due to the chronic nature of endometriosis, further research is needed to assess whether benefits from TENS units are sustained longer-term.\n\nA cross sectional survey61 of 113 women with pelvic, perineal pain, dyspareunia or endometriosis was conducted to gather information regarding patient cannabis use. 26/113 (23%) participants reported cannabis use, of which only 5/26 obtained cannabis through a medical programme, 25 had complete data and were analysed. 15/25 (60%) used a combination of cannabidiol (CBD) and tetrahydrocannabinol (THC). There was no significant difference between the demographics of cannabis users and nonusers. Overall, 24/25 (96%) of participants reported improvement in symptoms such as pain, depression and sleep disturbance with the use of cannabis. It is important to note that participants from both groups also utilised alternative medications and therapies, and therefore reported symptom improvement cannot be confidently solely attributed to cannabis use.\n\nTraditional Chinese medicine (TCM)\n\nZhao et al.62 performed a non-blinded RCT of 320 patients undergoing endometriosis surgery to investigate the effects of TCM (activating blood circulation and removing blood stasis treatment based on syndrome differentiation; n = 131) and Western medicine (GnRH agonist or progesterones; n = 141) on QOL postoperatively.\n\nPre-treatment WHOQOL-BREF scores, a QOL assessment tool with four domains including physical health, psychological, social relationships and environment, showed no significant difference between the two groups (p > 0.05), however post-treatment scores in the TCM group were significantly improved (p < 0.05) and the scores of 4 items (mobility, activities of daily living, sexual activity, QOL score) were also statistically significantly better (p < 0.05).\n\nFlower et al.63 published a Cochrane review assessing the effects of Chinese herbal medicine (CHM) for endometriosis, however only 2 RCTs were included (n = 158), neither of which assessed CHM vs. placebo. The first showed no significant different in ERPP between CHM and gestrinone administration post laparoscopic treatment (95.65% vs. 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). Combined oral CHM and herbal enema provided better improvement in dysmenorrhoea than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). There was no significant difference in lumbosacral pain, rectal discomfort, or vaginal nodule tenderness between CHM and danazol. Flower reports a paucity of robust studies assessing the effects of CHM and that the current studies available have been too small to apply statistical analysis.\n\n\nDiscussion\n\nThe previous cornerstones of endometriosis care have been shaken. Neuromodulators are less effective than assumed,6 a meaningful proportion do not get pain relief from surgery3 and ⅓ do not respond to progesterone. Complementary, self-management and lifestyle approaches are moving from fringe interest into mainstream endometriosis care.\n\nA historic RCT64 has shown multimodal holistic approaches yield superior outcomes to early laparoscopy in CPP.\n\nCurrent endometriosis centre accreditation weights bowel surgery heavily but patient education and signposting to holistic evidence-based care is left to enthusiastic HCPs, specialist nurses and patient charities, resulting in care inequities. Accreditation hinges on a multidisciplinary team of surgeons/urologists, but not with pelvic pain physiotherapists, nutritionists and psychologists.\n\nNumerous calls for more research into complementary approaches need to be answered by appropriate funding.\n\nWithin a patient journey, complementary approaches could be used in the following models as a primary approach or in conjunction with routine treatment.4\n\n1. Future women’s health hubs can identify DIE, likely to respond to surgery with specialised scanning even before referral to secondary and tertiary care. Models initiating this in the community would improve patient journeys and shorten the delay in endometriosis patients accessing care.\n\n2. Peri-operatively in the context of pre- and rehabilitation: surgery should no longer be seen in isolation but embedded in education and self-care. Clinicians observe patients recover faster and better from endometriosis surgery if they go into surgery having practised pre-habilitation.\n\n3. An adjunct to hormonal, surgical and pain-relieving western approaches.\n\n4. In the future, complementary and self-care techniques may be used in prevention of disease recurrence, whereas today the only evidence base is in hormonal manipulation65 but future evidence may enable clinicians to recommend preventive approaches.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nSmolarz B, Szyłło K, Romanowicz H: Endometriosis: Epidemiology, Classification, Pathogenesis, Treatment and Genetics (Review of Literature). Int. J. Mol. Sci. 2021; 22(19). PubMed Abstract | Publisher Full Text | Free Full Text\n\nZheng P, Zhang W, Leng J, et al.: Research on central sensitization of endometriosis-associated pain: a systematic review of the literature. J. Pain Res. 2019; 12: 1447–1456. PubMed Abstract | Publisher Full Text\n\nSingh SS, Gude K, Perdeaux E, et al.: Surgical Outcomes in Patients With Endometriosis: A Systematic Review. J. Obstet. Gynaecol. Can. 2020; 42(7): 881–888.e11. Publisher Full Text\n\nBall E, Karavadra B, Kremer-Yeatman BJ, et al.: Systematic review of patient-specific pre-operative predictors of pain improvement to endometriosis surgery. Reprod. Fertil. 2021; 2(1): 69–80. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nFraga MV, Oliveira Brito LG, Yela DA, et al.: Pelvic floor muscle dysfunctions in women with deep infiltrative endometriosis: An underestimated association. Int. J. Clin. Pract. 2021; 75(8): e14350. PubMed Abstract | Publisher Full Text\n\nda Silva JP , de Almeida BM , Ferreira RS, et al.: Sensory and muscular functions of the pelvic floor in women with endometriosis - cross-sectional study. Arch. Gynecol. Obstet. 2023; 308(1): 163–170. Publisher Full Text\n\nArena A, Degli Esposti E, Cocchi L, et al.: Three-Dimensional Ultrasound Evaluation of Pelvic Floor Muscle Contraction in Women Affected by Deep Infiltrating Endometriosis: Application of a Quick Contraction Scale. J. Ultrasound Med. 2022; 41(12): 2973–2979. PubMed Abstract | Publisher Full Text\n\nDel Forno S, Arena A, Alessandrini M, et al.: Transperineal Ultrasound Visual Feedback Assisted Pelvic Floor Muscle Physiotherapy in Women With Deep Infiltrating Endometriosis and Dyspareunia: A Pilot Study. J. Sex Marital Ther. 2020; 46(7): 603–611. Publisher Full Text\n\nDel Forno S, Arena A, Pellizzone V, et al.: Assessment of levator hiatal area using 3D/4D transperineal ultrasound in women with deep infiltrating endometriosis and superficial dyspareunia treated with pelvic floor muscle physiotherapy: randomized controlled trial. Ultrasound Obstet. Gynecol. 2021; 57(5): 726–732. PubMed Abstract | Publisher Full Text\n\nMira TAA, Buen MM, Borges MG, et al.: Systematic review and meta-analysis of complementary treatments for women with symptomatic endometriosis. Int. J. Gynaecol. Obstet. 2018; 143(1): 2–9. PubMed Abstract | Publisher Full Text\n\nPayne JA: Acupuncture for Endometriosis: A Case Study. Med Acupunct. 31. United States: Copyright 2019, Mary Ann Liebert, Inc., Publishers; 2019; pp. 392–394.\n\nMartin BR: Multimodal Care for Headaches, Lumbopelvic Pain, and Dysmenorrhea in a Woman With Endometriosis: A Case Report. J. Chiropr. Med. 2021; 20: 148–157. 20. United States: © 2022 by National University of Health Sciences. Publisher Full Text\n\nYan Q, Li J, Zeng J: The role of acupuncture in the treatment of women with pain in endometriosis: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021; 100(49): e27582. Publisher Full Text\n\nBecker CM, Bokor A, Heikinheimo O, et al.: ESHRE guideline: endometriosis. Hum. Reprod. Open. 2022; 2022(2): hoac009. Publisher Full Text\n\nWang Y, Coyle ME, Hong M, et al.: Acupuncture and moxibustion for endometriosis: A systematic review and analysis. Complement. Ther. Med. 2023; 76: 102963. Publisher Full Text\n\nLi PS, Peng XM, Niu XX, et al.: Efficacy of acupuncture for endometriosis-associated pain: a multicenter randomized single-blind placebo-controlled trial. Fertil. Steril. 2023; 119(5): 815–823. PubMed Abstract | Publisher Full Text\n\nZhang SXJ, MacLeod RGK, Parmar G, et al.: Ohnut Versus a Waitlist Control for the Self-management of Endometriosis-Associated Deep Dyspareunia: Protocol for a Pilot Randomized Controlled Trial. JMIR Res. Protoc. 2023; 12: e39834. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTeoli D, An J: Transcutaneous Electrical Nerve Stimulation. StatPearls. Treasure Island (FL): StatPearls Publishing. Copyright © 2023, StatPearls Publishing LLC; 2023.\n\nArik MI, Kiloatar H, Aslan B, et al.: The effect of TENS for pain relief in women with primary dysmenorrhea: A systematic review and meta-analysis. Explore (N.Y.). 2022; 18(1): 108–113. PubMed Abstract | Publisher Full Text\n\nBridger C, Prabhala T, Dawson R, et al.: Neuromodulation for Chronic Pelvic Pain: A Single-Institution Experience With a Collaborative Team. Neurosurgery. 2021; 88(4): 819–827. Publisher Full Text\n\nGuy M, Foucher C, Juhel C, et al.: Transcutaneous electrical neurostimulation relieves primary dysmenorrhea: A randomized, double-blind clinical study versus placebo. Prog. Urol. 2022; 32(7): 487–497. PubMed Abstract | Publisher Full Text\n\nMira TAA, Yela DA, Podgaec S, et al.: Hormonal treatment isolated versus hormonal treatment associated with electrotherapy for pelvic pain control in deep endometriosis: Randomized clinical trial. Eur. J. Obstet. Gynecol. Reprod. Biol. 2020; 255: 134–141. Publisher Full Text\n\nCarrubba AR, Ebbert JO, Spaulding AC, et al.: Use of Cannabis for Self-Management of Chronic Pelvic Pain. J. Womens Health (Larchmt). 2021; 30(9): 1344–1351. PubMed Abstract | Publisher Full Text\n\nZhao RH, Liu Y, Tan Y, et al.: Chinese medicine improves postoperative quality of life in endometriosis patients: a randomized controlled trial. Chin. J. Integr. Med. 2013; 19(1): 15–21. PubMed Abstract | Publisher Full Text\n\nFlower A, Liu JP, Lewith G, et al.: Chinese herbal medicine for endometriosis. Cochrane Database Syst. Rev. 2012; 2012(5): CD006568. Publisher Full Text\n\nPeters AA, van Dorst E , Jellis B, et al.: A randomized clinical trial to compare two different approaches in women with chronic pelvic pain. Obstet. Gynecol. 1991; 77(5): 740–744. PubMed Abstract\n\nZheng Q, Mao H, Xu Y, et al.: Can postoperative GnRH agonist treatment prevent endometriosis recurrence? A meta-analysis. Arch. Gynecol. Obstet. 2016; 294(1): 201–207. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "271069",
"date": "02 Jul 2024",
"name": "D Raimondo",
"expertise": [
"Reviewer Expertise endometriosis"
],
"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 abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding.\nIntroduction: The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2])\nMethods: The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies.\nResults: The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies.\nConclusions: The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact.\nGraphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal..\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": "12726",
"date": "08 Nov 2024",
"name": "Jessica Desai",
"role": "Author Response",
"response": "We thank you for the suggestions and have made the following adjustments to our paper: Abstract: The abstract is well-structured and provides a clear overview of the topic. However, it could benefit from a concluding sentence that highlights the clinical significance of the findings to enhance reader understanding. - Abstract concluding sentence adjusted Introduction: The introduction is comprehensive and provides adequate context on endometriosis and the challenges associated with its treatment. However, it could benefit from emphasizing more recent research, particularly from the last two to three years. Please discuss on the iatrogenic risk of endometriosis surgery and not only on the risk of recurrence (i.e. Ref [1,2]) - Please refer to reference 6 and 7 cited in the amended submission Methods: The methodology section is detailed and rigorous but could use some clarifications. Inclusion and Exclusion Criteria: Provide more details on the criteria used to include or exclude specific studies. Search Methodology: Describe the databases used and the search terms applied more specifically. Quality Assessment: Describe the metrics or tools used to evaluate the quality of the included studies. - Inclusion and exclusion criteria, search methodology and quality assessment sections added to paper Results: The results are well-presented and supported by a solid evidence base. However, some sections could benefit from more synthesis to improve readability. Nutrition: The information is detailed and pertinent, but a summary table could help visualize the effects of different dietary interventions better. Acupuncture: The acupuncture section is thorough but could benefit from a discussion on the limitations of the cited studies. - Limitations of paper reference 62 has been added Conclusions: The conclusions effectively summarize the key points of the article. However, reinforcing the message on the importance of integrating holistic strategies into clinical practice could enhance the impact. - Conclusion has been amended with statement on the importance of integration into clinical practice Graphs and Tables: Including more graphs and tables to visualize key data could improve the manuscript's comprehensibility and visual appeal.. - Please refer to Table 1"
}
]
},
{
"id": "292395",
"date": "22 Jul 2024",
"name": "Philippa Saunders",
"expertise": [
"Reviewer Expertise Reproductive biologist",
"specialising in women's health conditions including endometriosis. Translational research focused on improving range of treatments for chronic pelvic pain including self management strategies."
],
"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\nEndometriosis is an incurable disorder and as the authors correctly state patients are often keen to try non-medical approaches to manage symptoms including chronic pain, bloating and fatigue. Some approaches including physiotherapy are often included in multidisciplinary care and information on patient websites includes a wide range of complementary therapies some of which are discussed in this review [https://www.endometriosis-uk.org/].\nThe authors are to be commended on bringing together information about a very wide range of potential interventions and their assessment that many individuals with symptomatic endometriosis are keen to explore self management and alternative therapies as part of their care plan is something increasingly reported by health care professionals. The section entitled ‘Recent findings’ makes some dogmatic statements and it was not clear they were backed up by the latest data – this was particularly true of nutrition which is a fast moving field.\nGiven the importance of the topic it is of concern that there appears to be an overall lack of ‘balance’ in the paper with a lot of emphasis in the first section placed on a systematic reviews – REFs 1-5, 8,9,12. In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?]\nIt is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. Authors are referred to a number of recent reviews related to the impact of diet, inflammation and the gut brain axis as sources of information. Additional References Esprit2 trial has a published protocol [Ref -1]. Reference 6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7]\nAdd more details from Ref 64 – this paper is from 1991 – any follow up papers?\n\nIs the topic of the review discussed comprehensively in the context of the current literature? No\n\nAre all factual statements correct and adequately supported by citations? No\n\nIs the review written in accessible language? Yes\n\nAre the conclusions drawn appropriate in the context of the current research literature? No",
"responses": [
{
"c_id": "12727",
"date": "08 Nov 2024",
"name": "Jessica Desai",
"role": "Author Response",
"response": "We thank you for the suggestions and have made the following adjustments: In some parts of the text it is hard to know if the results discussed relate to individuals with CPP or those with CPP/Endo so careful re-reading and clarification of is advised (examples include yoga, TENS, mindfulness). [table of mind and body therapies?] - Clarification has been made on relation to CPP/endometriosis throughout the text It is recommended that the authors assemble information from relevant high quality original information from trials in tables – this would be more useful to the reader than simple text. - Please see Table 1 Esprit2 trial has a published protocol [Ref -1]. - Espirit2 trial protocol has now been referenced, please see reference 5 Reference 6 is to a protocol – the trial has been completed and the correct reference is [Ref -2] - Reference amended In section on nutrition it would be useful to mention GWAS and other data that support patient experience of IBS-like symptoms in association with endometriosis (includes abdominal bloating [Ref-3], diarrhoea etc). Recent paper [Ref-3] - Please see use of reference 23 in our paper No mention of botox for treatment of pelvic floor pain although there are reports it is effective · [Ref -4] - Section on botulinum toxin added to paper The section on cannabinoids is very brief which seems at odds with the widespread use of CBD in management of chronic pain, in some countries they are prescribed and there are several trials for endometriosis CPP underway – add more references. [Ref 5-7] - CBD section has been expanded, please see references 69, 70 Add more details from Ref 64 – this paper is from 1991 – any follow up papers? - Section expanded, please refer to reference 76"
}
]
}
] | 1
|
https://f1000research.com/articles/13-359
|
https://f1000research.com/articles/13-1147/v1
|
07 Oct 24
|
{
"type": "Study Protocol",
"title": "Psychological well-being of travellers on long-distance shipping voyages: A systematic review protocol",
"authors": [
"Audifax Kpeno",
"Twinkle Rout",
"Pratap Kumar Sahu",
"Nachieketa Khamari Sharma",
"Surjeet Sahoo",
"Deepak Kumar Pattanaik",
"Twinkle Rout",
"Pratap Kumar Sahu",
"Nachieketa Khamari Sharma",
"Surjeet Sahoo",
"Deepak Kumar Pattanaik"
],
"abstract": "The psychosocial well-being of every individual is as important as the well-being of long-distance voyages, especially that they have to spend longer hours and days travelling to their destinations with all the experiences of adventure and adversities characterizing the journey. The aim of this systematic review is to explore the psychosocial well-being of long-distance travellers on board shipping vessels to gain an understanding of their psychological and social well-being with the objective of ameliorating the adversities associated with these travels. A systematic review will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (2020) statement. The databases to be searched for the data will be limited to Scopus, Web of Science, and Advanced Google Scholar using keywords selected by the reviewers. Meta-analysis, narrative synthesis, or both will be used depending on the extent of heterogeneity across eligible observational studies included in the review. Some specific countries will be selected for data extraction, and only data published in English will be included. It is expected that the findings from this review will bring to bear if these categories of travellers are prone to risks that affect their psychosocial wellbeing and if so discovered. This protocol was registered with the PROSPERO. PROSPERO registration number: CRD42024517277(08/03/2024)",
"keywords": [
"Psychosocial",
"well-being",
"mental-health",
"shipping voyages",
"Seafarers"
],
"content": "Introduction\n\nThe role of seafarers is peculiar in that their work is not restricted by time; they are constantly working both onshore and offshore. Hence, they find their social lives circumscribed,1 predisposing them to a myriad of psychological and physical challenges.2 Seafarers are often onboard a ship for several long hours faced with adverse weather conditions such as “high pitched noises, vibrations, cold spells, high temperatures and unstable moisture conditions”3 which does not augur their physical health.\n\nSettling on a definition for long distance travel has been described as challenging4 in a white paper where long-distance travel has been defined broadly as “out-of-town” trips. These trips have been limited to intercity or inter-regional trips and may not involve overnight stays.4 However, for the purpose of our review, long-distance voyages are defined to include maritime journeys that involve the transportation of goods of people across vast stretches of the ocean, typically spanning significant distances between distant ports or destinations. In addition to this definition, these voyages often entail extended durations at sea and may traverse multiple continents or regions.\n\nSea travel or travel by ocean on long-distance shipping voyages is a journey characterized by both adventure and adversity. Notwithstanding all the turbulence associated with sea travel, the sea is seen as a temporary home for those who have to undertake long-distance travel. An exploration of the psychological well-being of those who call the sea their temporary home cannot be overly emphasized, as it will help bring out the complexities associated with shipping voyages. This will shed light on the various dimensions that shape their mental and emotional states amidst the challenges of maritime life.\n\nAt the crust of this journey of exploration lies the concept of well-being, defined as a multidimensional construct that serves as a compass guiding individuals towards a life of satisfaction, happiness, and overall quality.5 Rooted in both subjective experiences and objective indicators, well-being includes both internal and external factors that shape one’s perception of life satisfaction and fulfilment.5 As travellers embark on their maritime journeys, their well-being is linked to their ability to overcome the challenges of life at sea while maintaining a sense of inner equilibrium and contentment.\n\nComplementing the exploration of well-being is the examination of the concept of psychosocial well-being, which encompasses the mental, emotional, and social dimensions of health. Embedded within this construct are psychological factors such as self-esteem and coping mechanisms, social factors such as social support and interpersonal relationships, and emotional factors such as mood regulation and stress management.6 As travellers face the challenges of long-distance shipping voyages, their psychosocial well-being serves as a guide, providing support and direction to cope with the challenges and changes that come with living and working on a ship, influencing their ability to adapt, connect, and thrive amid the vast expanse of the open sea.\n\nThis review seeks to achieve the following objectives: to assess the prevalence of psychosocial issues among travellers on long-distance shipping voyages; to identify the factors contributing to psychosocial challenges among travellers; and to examine the impact of psychosocial issues on the well-being and performance of travellers to evaluate existing interventions and support systems for promoting psychosocial well-being among travellers. We intended to answer the following research questions:\n\nQ1: What are the subjective experiences of seafarers during long-distance voyages and how do they perceive and cope with the challenges they encounter?\n\nQ2: What role do social support networks play in mitigating psychosocial challenges among seafarers and how do these networks operate within the maritime environment?\n\nQ3: What are the key factors influencing psychosocial well-being among seafarers, including work-related stressors, voyage duration, and interpersonal relationships?\n\n\nMethods\n\nThis systematic review will be conducted considering the standard reporting format of the preferred reporting items for systematic review and meta-analysis (PRISMA, 2020) protocol guidelines.\n\nWe established specific eligibility criteria to inform the inclusion of studies in the review. Our criteria were designed to ensure that the included studies focused on individuals engaged in long-distance shipping voyages and investigated psychosocial factors, experiences, or interventions related to this context. Studies that capture individuals, such as seafarers, crew members, and maritime workers employed in long-distance shipping voyages, are included. For example, studies exploring the impact of isolation, confinement, cultural adaptation, job stress, social support, mental health services, and coping mechanisms among individuals on long-distance shipping voyages were considered eligible.\n\nOn the other hand, we will exclude studies that focus solely on populations not directly related to long-distance shipping voyages, such as studies on short-distance maritime workers or land-based occupations. Additionally, studies focusing solely on passengers or tourists rather than crew members or maritime workers were excluded from our review.\n\nFurthermore, to ensure that the selected studies align with the objectives of our review, we included studies that measured various aspects of psychosocial well-being, including but not limited to mental health, emotional well-being, job satisfaction, social connectedness, quality of life, stress, burnout, resilience, and coping strategies among individuals engaged in long-distance shipping voyages. This encompasses the exploration or measurement of factors such as depression, stress, anxiety, social support, and coping mechanisms, aligning with the objectives of this review. Additionally, eligible studies should measure the prevalence of psychosocial well-being among shipping voyages and address the aspects of job satisfaction and quality of life related to long-distance voyages. Studies lacking relevant psychosocial well-being outcomes or measures, as well as those focusing solely on organizational factors, technical aspects, or non-psychosocial aspects of maritime work, were excluded from our review.\n\nThe outcomes of this review will include measures of depression, anxiety, social support, job satisfaction, and QoL. Studies that provide acceptable standard definitions for these concepts were considered. Definitions for depression and anxiety should not deviate widely from those given by Beck,7 as this definition is considered the most acceptable. Quality of life should be defined by the World Health Organization (WHO). It should encompass an individual’s subjective life experiences, including their physical, mental, social, and emotional well-being.8 Studies that have operationalized these constructs with standardized scales, including but not limited to the HAM-A and HAM-D for anxiety and depression, respectively, the Patient Health Questionnaire (PHQ),9 Job Descriptive Index (JDI),10 Job In General (JIG) scale,11 and Minnesota Satisfaction Questionnaire (MSQ)12 will all be included in this review.\n\nPrimary studies that used qualitative or quantitative methods will be included in the review. This allowed a broad range of studies to be included. Mixed-methods studies are also eligible for inclusion, as they can provide valuable insights by combining qualitative and quantitative approaches.\n\nThis review will include all studies that used participants who have had long-distance shipping voyages, regardless of gender or geographical orientation. However, it will exclude children below the age of 15, as they may not be able to corroborate their experience well enough to inform generalization.\n\nThis review includes studies conducted in India, Denmark, the United Kingdom, Sweden, Ireland, Germany, South Africa, Norway, and the Czech Republic. These countries were selected because of their high shipping voyage rate. Particular attention of the reviewers is paid to India because we intend to leverage the results of this review to conduct primary research within the Indian shipping voyage space.\n\nThe researchers intended to develop search strategies for eligible literature using keywords related to maritime activities and mental health. Databases, such as Scopus and Web of Science, will be searched using keywords. These databases were selected as they are considered to hold large volumes of data worldwide, so the potential of covering most of the studies is very high. Advanced Google search engines will also be searched to capture other data that otherwise might not have been indexed in these two major databases (Scopus and Web of Science). Dissertations and theses were excluded because the researchers intended to work with only published records.\n\nThis systematic review focuses exclusively on published records and peer-reviewed journal articles. Unpublished theses and dissertations will be excluded from the review owing to potential limitations in access, quality control, or potential bias in unpublished work. All searches will be limited to studies published in English and will involve only human subjects. It is anticipated that this review will be completed in September 2024. That is, the expected end-year search for the data will end in 2024.\n\nThe literature search will employ Boolean Operators (AND and OR) along with side keywords for each of the databases to be searched. For instance, psychosocial OR “well-being” OR “mental-health” OR “Shipping Voyages” OR Seafarers; for the first phase of the search; the other phase will combine keywords such as psychological AND “shipping voyages” AND Seafarers. This formula was applied to both databases from which the search was carried out. The search was limited to countries in the study setting.\n\nThe search was conducted in two phases. The initial phase will focus on identifying studies conducted within India, given the specific context and relevance of the topic to this geographic region, as well as the fact that the researcher intends to rely on the findings of this review to carry out an original study. Subsequently, a broader search will be carried out to capture relevant literature from other named countries, as indicated in the study setting, to ensure comprehensive coverage of the available evidence.\n\nThe statement for Reporting Literature Searches in Systematic Reviews (PRISMA-S)13 will be relied upon as a guide for reporting our search results. The two authors (AK and TR) will carry out the search independently, and AK and PD will compile the search results and remove duplicates.\n\nAt this stage of the review, three authors, AK, TR, and PD, will independently screen the titles and abstracts of the identified records using eligibility criteria. Subsequently, they will independently screen the full text of other records for which decisions could not be reached after their titles and abstracts were screened. On one hand, through a one-on-one interaction between PD, AK and TR, a discussion will be held to resolve any discrepancies that would arise during the screening process. After reaching an agreement on the records to be included by these three authors, NKS and SS will give a final validation to these records owing to their expertise in maritime and Psychological research respectively.\n\nTo ensure that the findings of all the records extracted are free from the risk of bias, based on reliable and unbiased evidence, two of the reviewers, NKS and PKS, will use the Cochrane Collaborations’ Risk of Bias tool14 to systematically evaluate the risk of bias in the extracted records. This must be performed to meet the standard set for the systematic review protocol. In a systematic review, minimizing bias is a core component of the review,15 and one of the most preferred means to achieve this is by employing the most appropriate tools. Many tools exist for the execution of this process. However, the Cochrane Collaboration Risk of Bias tool is the most preferred and widely used tool. This affords researchers the opportunity to consider plausible limitations of the studies to be included in the review in order to obtain reliable conclusions.\n\nTo determine the reliability and credibility of the individual documents, a quality assessment was performed by two authors with several years of experience in the field of psychiatry. One performed the initial assessment, and the other crosschecked. The quality rating was premised on the following criteria: “Selection bias,” “random sequence generation,” “allocation concealment,” “reporting bias,” “other bias,” “performance bias,” “detection bias,” “data collection methods” and “attrition bias”.11 Each of the articles included in the study was assessed for bias using the Cochrane Collaboration Risk of Bias tool.\n\nOur choice of approach for data synthesis is informed by the degree of heterogeneity observed. We will use meta-analysis, narrative synthesis, or both. Meta-analysis, a statistical method employed when combining results of large samples of data (records) to be included in a study, provides, to a larger extent, the reliability or precision of the estimates on any treatment effects.16 Meta-analysis involves pooling data from individual studies, analyzing them collectively, and often calculating a weighted average effect size.16 On the other hand, narrative synthesis involves a qualitative approach to synthesize evidence from multiple studies. Here, rather than pooling data and collecting statistical analyses, narrative synthesis focuses on summarizing and interpreting findings from individual studies in a narrative format. It includes the description of patterns, themes, and discrepancies across studies, providing a qualitative understanding of the topic under investigation.16\n\nThe researchers’ choice of any or both of these methods is contingent on the outcome of the selected records. However, in the event where heterogeneity will be observed among studies, it will be incumbent to use narrative synthesis, since the application of meta-analysis in this situation will be challenging as the studies will be too different to be combined. In the same instance of heterogeneity prevalence, the researcher will follow the three-step approach to narrative synthesis to synthesize the results included in the study.17 These steps include organizing the description of the studies into logical categories, analyzing the findings within each of the categories, and synthesizing the findings across all included studies.17 Tables and graphs are used to support narrative synthesis or qualitative summary.\n\n\nDiscussion\n\nThis discussion will focus on three thematic areas: beginning with the implications for this planned review, the significance of the topic, and addressing the research objectives of the review.\n\nThis systematic review has significant implications for research, practice, and policies in several areas. From a research perspective, the findings of this review have the potential to advance knowledge in maritime health and occupational psychology. Identifying factors contributing to psychosocial challenges among travellers can guide future research efforts to explore causal mechanisms, risk factors, and protective factors associated with well-being in this population. Additionally, the review highlights gaps in the literature and opens further investigation into the understudied aspects of psychosocial well-being among travellers.\n\nIn terms of practice, the review findings can inform the development of interventions and support strategies aimed at promoting the well-being of travellers on long-distance shipping voyages. This review will delve into synthesizing effective practices and identifying areas for improvement to guide shipping companies, healthcare providers, and other stakeholders in their implementation of effective strategies to address psychosocial challenges such as isolation, stress, and cultural differences. From a policy perspective, this review provides valuable insights into the regulatory frameworks and guidelines needed to ensure the health and well-being of travellers in the maritime industry.\n\nThis review will shed light on the potential impact of psychosocial issues on the health, safety, and performance of individuals in this population, as well as the broader implications for maritime industry stakeholders, regulatory agencies, and policymakers. Applied psychology research has extensively explored stress-related factors within transportation contexts, including those related to drivers and commuters. While much of this research has centered on terrestrial transportation, there are parallels to be drawn with voyages on long-distance shipping. The maritime environment, characterized by prolonged periods away from home, isolation, and the demands of shipboard life, presents unique psychosocial challenges for individuals. Understanding the impact of these stressors on voyagers’ well-being and performance is crucial for ensuring the safety and efficiency of maritime operations. Psychological factors, such as personality disposition, attitudes towards voyage destinations, and coping mechanisms, play significant roles in shaping the experiences of travellers. Moreover, issues such as fatigue, boredom, and loss of alertness can have profound effects on the operational effectiveness and safety at sea. By addressing these psychosocial issues, this review aims to provide insights that will guide maritime industry stakeholders in making informed policy decisions to support voyagers’ well-being and enhance operational outcomes.\n\nThis review systematically examines the prevalence of psychosocial issues among travellers on long-distance shipping voyages by reviewing existing evidence from relevant studies to provide insights into the frequency and scope of these issues within the target population. Through a thorough examination of the literature, this review identifies the factors that contribute to psychosocial challenges among travellers. We will synthesize findings from diverse studies, including qualitative research, observational studies, and quantitative analyses, to gain an appreciable understanding of the contributing factors, such as isolation, confined living spaces, job stress, and cultural differences. This review will assess the impact of psychosocial issues on the well-being and performance of travellers by synthesizing evidence on relevant outcomes, such as mental health, emotional well-being, job satisfaction, and job performance. As we analyzed the reported associations between psychosocial challenges and these outcomes, this review will provide insights into the broader implications for individual health, safety, and organizational effectiveness.\n\nThe PRISMA-P Checklist for the systematic review protocol18 has been attached as an extended data. This protocol was registered with the PROSPERO. Prospero registration number: CRD42024517277\n\n\nDisclosure\n\nAll authors have approved the final article.\n\n\nEthics and consent\n\nEthical approval and consent were not required\n\n\nStrengths and limitations of the review\n\n\n\n• The review will be reported in accordance with the PRISMA frame protocol\n\n• This review will add to the few reviews, if not the first of its kind, regarding the psychosocial well-being of long-distance travellers.\n\n• This review will examine three senior experienced researchers contributing to the data extraction and inclusion process to ensure that the evidence that will be adduced will stand the test of time.\n\n• The exclusion of some of the databases in the data extraction process may hinder the inclusion of records that might not have been indexed in the three databases employed.\n\n\nDisclosure\n\nAll authors have approved the final article.\n\n\nAvailability of data\n\nThis is a protocol, and there were no data at this stage of the study.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZENODO: Prisma – P Checklist for Psychological well-being of travelers on long-distance shipping voyages: A systematic review protocol, https://doi.org/10.5281/zenodo.13838158 18\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgement\n\nThe authors are highly grateful to the research members of IMS and SUM Hospital, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, for providing support during the work.\n\n\nAcknowledgement\n\nThe authors are grateful to the faculty members of Siksha O Anusandhan (Deemed to be University), Bhubaneswar for their valuable contributions.\n\n\nReferences\n\nJensen HJ, Oldenburg M: Potentially traumatic experiences of seafarers. J. Occup. Med. Toxicol. 2019; 14(1): 4–9.\n\nOldenburg M, Baur X, Schlaich C: Occupational risks and challenges of seafaring. J. Occup. Health. 2010; 52(5): 249–256. PubMed Abstract | Publisher Full Text\n\nSlišković A, Penezić Z: Occupational stressors, risks and health in the seafaring population. Rev. Psychol. 2015; 22(1–2): 29–39. Publisher Full Text\n\nAultman-Hall L: Incorporating long-distance travel into transportation planning in the United States. National Center for Sustainable Transportation; 2018.\n\nDiener E, Lucas RE, Oishi S: Advances and open questions in the science of subjective well-being. Collabra. Psychol. 2018; 4(1): 1–49. Publisher Full Text\n\nTokunaga RS, Rains SA: An Evaluation of Two Characterizations of the Relationships Between Problematic Internet Use, Time Spent Using the Internet, and Psychosocial Problems. Hum. Commun. Res. 2010; 36(4): 512–545. Publisher Full Text\n\nRemes O, Francisco J, Templeton P: Biological, Psychological, and Social Determinants of Depression: A Review of Recent Literature. Brain Sci. 2021; 11(12). PubMed Abstract | Publisher Full Text | Free Full Text\n\nKarimi M, Brazier J: Health, Health-Related Quality of Life, and Quality of Life: What is the Difference? PharmacoEconomics. 2016; 34(7): 645–649. Publisher Full Text\n\nFord J, Thomas F, Byng R, et al.: Use of the Patient Health Questionnaire (PHQ-9) in Practice: Interactions between patients and physicians. Qual. Health Res. 2020; 30(13): 2146–2159. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVan HD, Nhung DTH, Linh TM: Identifying work-related factors influencing job satisfaction using job descriptive index questionnaire: a study of IT companies in Hanoi. J. Int. Econ. Manag. 2021; 21(1): 63–85. Publisher Full Text\n\nLopes S, Chambel MJ, Castanheira F, et al.: Measuring job satisfaction in Portuguese military sergeants and officers: Validation of the job descriptive index and the job in general scale. Mil. Psychol. 2015; 27(1): 52–63. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVigan FA, Giauque D: Job satisfaction in African public administrations: a systematic review. Int. Rev. Adm. Sci. 2018; 84(3): 596–610. Publisher Full Text\n\nOláh J, Krisán E, Kiss A, et al.: PRISMA statement for reporting literature searches in systematic reviews of the bioethanol sector. Energies. 2020; 13(9): 1–35. Publisher Full Text\n\nMinozzi S, Cinquini M, Gianola S, et al.: The revised Cochrane risk of bias tool for randomized trials (RoB 2) showed low interrater reliability and challenges in its application. J. Clin. Epidemiol. 2020; 126: 37–44. PubMed Abstract | Publisher Full Text\n\nCooper C, Booth A, Varley-Campbell J, et al.: Defining the process to literature searching in systematic reviews: A literature review of guidance and supporting studies. BMC Med. Res. Methodol. 2018; 18(1): 1–14.\n\nCochrane A, Higgins NM, Fitzgerald O, et al.: Early interventions to promote work participation in people with regional musculoskeletal pain: A systematic review and meta-analysis. Clin. Rehabil. 2017; 31(11): 1466–1481. PubMed Abstract | Publisher Full Text\n\nJohnson BT, Hennessy EA: Systematic reviews and meta-analyses in the health sciences: Best practice methods for research syntheses. Soc. Sci. Med. 2019; 233(3): 237–251. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKpeno A, Rout T, Sahu PK, et al.: & Nachieketa KS. PRISMA-P Checklist for the Systematic Review Protocol: Psychosocial Well-Being of Travellers on Long-Distance Shipping Voyages: A systematic review protocol 2024. Zenodo. Publisher Full Text"
}
|
[
{
"id": "332927",
"date": "24 Oct 2024",
"name": "Giulio Nittari",
"expertise": [
"Reviewer Expertise Telemedicine",
"telepharmacy",
"epidemiology",
"neurodegeneration 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\nOverall a good evaluation of the topic selected. some more elaboration and editing is necessary to complete the manuscript. In the introduction section, all stressful factors should be mentioned: objective and subjective ones, and then focus to the ones of study. (can use reference: Ref 1\nlimitations of study should include except from gender discrepancies, also age discrepancies. Control group should be edited to follow the study group especially in respect of female to male ratio, so as to have a valid conclusion at the end Possible treatment/management in order to reduce death anxiety should be expanded also in a paragraph to include frequent psychological consults both on board/telemedicine and off-board, and also a mention of telemedicine to combat the covid pandemic.\n\nSome good articles for this section can include:\n1. Ref 2 2. Ref 3\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? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
},
{
"id": "332925",
"date": "24 Oct 2024",
"name": "Francesco Buscema",
"expertise": [
"Reviewer Expertise Organizational Health Psychology",
"Seafarers Health",
"Psychosocial Risk Evaluation."
],
"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 carefully reviewed your manuscript. I believe the topic of this systematic review is highly relevant and important for bridging a significant gap in the literature. However, to ensure the manuscript meets the highest standards for indexing, I would like to suggest some revisions. Protocol Structure: If this manuscript is intended as a protocol, please ensure it adheres to the Guidelines for Preparing a Study Protocol article. The main body of the manuscript should focus on presenting the \"Protocol\" itself. Introduction Section: While the Introduction section generally aligns with the manuscript's objectives, I recommend a comprehensive revision for two primary reasons: 1) Clarity and Grammar and 2) References 1) Please review the section for grammatical errors and inconsistencies to enhance clarity. 2) Ensure that all claims and statements are supported by relevant references. Terminology: When discussing individuals working on ships, please use the term \"seafarers\" rather than \"travellers.\" Seafarers are professionals engaged in maritime work and not simply travelers. Eligibility Criteria: To provide a clear understanding of the studies included in your review, please be more specific about the eligibility criteria. The phrase \"for example\" implies that there are other studies not explicitly listed. Please also clarify the specific types of seafarers included in your review. The term \"seafarers\" can encompass a wide range of workers, such as deck officers, engineers, and catering personnel. Exclusion Criteria: Please provide a more detailed explanation of the exclusion criteria. What specific psychosocial well-being outcomes or measures are excluded, and how do you define \"organizational factors,\" \"technical aspects,\" or \"non-psychosocial aspects of maritime work\"? QoL: Please specify the definition of QoL that you will be using in your review. Eligibility Criteria for Studies: Consider adding the following sentence to the paragraph related to eligibility criteria: \"Studies that provide clear and acceptable definitions for these concepts were considered.\" Definition of QoL: If you intend to use the WHO's definition of QoL, please state this explicitly. Other Scales: If you are including scales beyond those explicitly mentioned, please provide a more comprehensive list. PRISMA-P Checklist: Please ensure that the PRISMA-P Checklist in the attachment accurately reflects all search strategies conducted, including those using databases other than Scopus.\nI believe that addressing these points will significantly enhance the quality and clarity of your manuscript.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? No\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1147
|
https://f1000research.com/articles/13-307/v1
|
22 Apr 24
|
{
"type": "Research Article",
"title": "Neck pain and distance learning: A pain in the neck for university students during COVID-19",
"authors": [
"Awab Musaad Mohamed",
"Mohamad Abdulkafi Abbara",
"Sara Alaaeldin Bashier",
"Danya Aasim Elkhidir",
"Amal Hussein",
"Anu Vinod Ranade",
"Awab Musaad Mohamed",
"Mohamad Abdulkafi Abbara",
"Sara Alaaeldin Bashier",
"Danya Aasim Elkhidir",
"Amal Hussein"
],
"abstract": "Objective The shift to online learning during COVID-19 led to increased musculoskeletal discomforts and impacted students’ quality of life. Neck pain, once a minor issue, has become more prevalent due to prolonged electronic device use in new learning methods. This study aims to measure the prevalence of neck pain among University of Sharjah (UOS) students during the COVID-19 online learning period and to investigate the factors that provoked it.\n\nMethods This cross-sectional study used an online survey distributed to UOS students via social media from February 16 to March 12, 2021. Demographic data, Neck Disability Index (NDI) assessments, and pain management information were gathered and analyzed using SPSS 24 through univariate and bivariate methods.\n\nResults The prevalence of neck pain during COVID-19, among 325 UOS students was found to be 62.7%, 64.41% of which had neck pain at the time of doing the survey. The mean NDI percentage point was 19.19%. The most common location of pain was the back of the neck 38.77%). Participants reported prolonged sitting (81.23%) while leaning forward as the most prevalent cause of their neck pain. Bivariate analysis showed that the most significant factors affecting the NDI were lifting, personal care, headaches, concentration, sleeping, recreational activities, reading, anxiousness, depression, and work. Moreover, subjects who did not seek medical attention treatment had significantly higher NDI scores as compared to those who did (83.89 vs 125.80, p=0.002).\n\nConclusion By determining the prevalence of neck pain among UOS students, this research can attract attention to the importance of postural changes and time spent in e-learning on neck pain, and the gaps of previously published articles can be filled. Future studies about neck pain and additional preventative measures should be catalyzed in the UAE.",
"keywords": [
"Neck pain",
"COVID-19",
"E- learning",
"musculoskeletal disorders"
],
"content": "Introduction\n\nNeck pain is a common condition that affects a significant proportion of the population. Despite its prevalence, it can have a substantial negative impact people’s lives, including their ability to work, sleep and participate in daily activities.1 The global prevalence of neck pain was 3551.1 per 100 000 people in 2017 with a DALY (disability adjusted life years) prevalence of 352.0 per 100 000 people.2 Chronic neck pain presents a significant burden on societies all over the world.3 Neck pain and other forms of chronic pain in general burdens the workers, increases sickness absence, and decreases productivity.4 Furthermore, it can exacerbate other co-existing conditions such as migraines,5 making it more challenging to manage these conditions effectively. Neck pain may lead to muscle morphology such as hypertrophy or atrophy, alteration in muscle fiber type, and reduced muscle strength.6\n\nIn 2018, 440 randomly chosen medical students at Jazan University in Saudi Arabia reported a prevalence of neck pain of 53.5%.7 According to other studies, using laptops and smartphones which many university students depend on all the time, has been identified as a significant risk factor of neck pain.8\n\nStudents in the United Arab Emirates (UAE) commonly experience musculoskeletal disorders (MSP) as one of the primary occupational health concerns.\n\nA study conducted in February 2020 among 368 dental students from Ajman University and Ras Al Khaimah College of Dental Sciences reported a prevalence of MSP 48.5% and 68.3% in the past week and year, respectively based on responses to questionnaire.9 The most frequent occupational health hazards faced by newly graduated dentists working in Abu Dhabi, Dubai and Sharjah, as reported in a study conducted on 733 individuals, are musculoskeletal disorders (MSP) at 68% and percutaneous injury at 42%.10\n\nThe prevalence of neck pain among 80 radiologists in the United Arab Emirates, comprising of male and female radiologists from nationalities, found a significant rise in the prevalence of neck pain after they started working in the radiology department in 2017. Also, the neck pain surpassed other common work-related symptoms such as back pain, knee pain and vision issues. The researchers speculated that poor body mechanics such as improper posture, repetitive movements and inadequate support may contribute to the development of neck pain.11\n\nThe COVID-19 pandemic, which was officially declared on March 11, 2020, has brought about extraordinary challenges in various aspects of life. Outbreaks have led to increased unemployment as well as compromise in education, physical and mental health, resulting in a profound impact on the world.12,13\n\nEducation was one of the fields that has been extremely affected during the COVID-19 pandemic with schools and universities globally have transitioned to distance education.14\n\nBlended and hybrid learning have continued to gain popularity and increase in value beyond the pandemic, mainly due to the necessity for novel and innovative teaching techniques, the potential of cloud-based applications, enhanced collaboration, and creativity.15 Additionally, lack of adherence to good ergonomic practices during online learning at home has led to an increase in reported cases of back pain and fibromyalgia pains.16 Unlike in the classroom, students are not obligated to follow proper ergonomics at home and take online classes while sitting on beds or sofas. These inappropriate prolonged sitting and studying posture have led to the development of musculoskeletal discomfort and complaints including neck pain.17,18 It is hypothesized that utilizing these devices may cause indirect tension in the neck muscles, eventually leading to neck pain and discomfort.6 According to a Hong Kong research, using electronic devices is associated with musculoskeletal disorders, particularly in the neck and shoulder region.11\n\nStudies have indicated that a lack of knowledge regarding effective strategies for pain management among university students can result in negative consequences for their musculoskeletal pain, leading to a decline in quality of life and potentially significant socioeconomic issues.19 Furthermore, students experiencing musculoskeletal pain, such as low back pain, may have poorer academic performance and higher levels of absenteeism compared to those without pain.20,21\n\nAlthough research has investigated the association between neck pain and electronic device use among university students, limited research has focused during the COVID-19 pandemic. University students may be more susceptible to neck pain due to the high demands of their academic work, which often require long periods of concentration in front of electronic devices. Furthermore, it is well-established that poor posture, such as slouching or holding the head in a forward position, can place significant stress on the neck and lead to pain and discomfort. However, despite the high prevalence of neck pain, there is limited research on the factors that may contribute to it, especially among the UAE population, and specifically among university students. Therefore, it is vital to investigate the potential risk factors for neck pain among university students, including the amount of time spent on electronic devices, the type of devices used, and the posture adopted during use.\n\nSuch research can provide valuable insights into the prevalence and potential causes of neck pain among this population and help to inform interventions and preventative measures to reduce the incidence of neck pain and improve the overall health and well-being of students.\n\nGaining insight into the factors that increase the likelihood of neck pain in university students can help create interventions such as modifying workstations, increasing breaks, setting reminders to adjust posture, and practicing exercises to improve posture and reduce muscle tension.\n\n\n\n• To measure the prevalence of neck pain among UoS students during online learning.\n\n• To identify factors that are associated with the intensity of the neck pain and to evaluate the psychosocial impact related to neck pain (interference of pain with daily activities and obligations, anxiousness, or depression).\n\n\nMethods\n\nThe study utilized an observational cross-sectional design using STROBE guidelines. The data was collected through questionnaires from a specific target population, which are the UoS students aged between 18-24. The accessible population was limited to students who were available on social media platforms since the questionnaire was posted online. Non-probability volunteer sampling was the chosen sampling method due to the challenges in accessing a vast number of UoS students and young adults during the study period. Moreover, the online questionnaire was disseminated through various social media platforms, and participation was voluntary.\n\nOur sample size (n) was determined to be 400 based on a 50% prevalence (P) and a 5% margin of error (ME), using the formula n=4P(1-P)/SE2.\n\nAll UoS students aged 17-24 studying in the Sharjah campus and able to do the survey.\n\nParticipants who reported neck pain prior to March 7th, 2020, which was determined based on their responses in the questionnaire; those who attributed their neck pain to events unrelated to online learning; individuals with recent trauma or surgery, and those with disabilities.\n\nThe expected prevalence of neck pain was set at 50% as no previous studies in the UAE had been found to address the issue. Using 50% as the expected prevalence, the highest possible value, ensured that the minimum required sample size could be achieved. However, the research team ensured that the questionnaire was made available to the largest possible number of individuals to reach the minimum required sample size and to increase the accuracy of the study.\n\nFor this study, a self-administered questionnaire was utilized to gather data. It consisted of the Neck Disability Index (NDI) questionnaire, designed to assess the impact of neck pain on daily functioning22,23 as well as additional questions exploring other factors associated with neck pain. Questionnaire was disseminated across various social media platforms, including WhatsApp, Facebook, Instagram, and others.\n\nComprising of five sections, the questionnaire consisted of 27 questions covering demographics, pain history, impact on daily activities and mental health, e-learning environment, and management. Most of the questions were close ended, designed to simplify the survey. Nevertheless, three questions were open-ended to provide participants the opportunity to provide comprehensive answers.\n\nPrior to commencing data collection, a pilot study involving 10-15 subjects was carried out in the 2020/2021 academic year. Upon receiving ethical approval, the questionnaire was distributed via social media platforms by each researcher during the spring semester of 2020/2021. Furthermore, the researchers invited their close friends and colleagues to participate, as they were part of the target population.\n\nSPSS 24 (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp.) was used to analyze the data, employing univariate analysis to generate descriptive statistics, such as frequency and measures of central tendency, as well as bivariate analysis to examine variable relationships. The SPSS license was obtained through the institutional SPSS software license of the University of Sharjah.\n\nInferential statistical tests, such as Chi-square, t-test, and Pearson correlation, were utilized based on the type of variables, with a significance level set at 5%.\n\nThe study obtained ethical clearance from the University of Sharjah research and graduate research ethics committee (REC-21-02-11-02-S) approval date 14.02.2021, with participation being voluntary, anonymous, and risk-free. Data collected were confidential and used exclusively for research purposes.\n\n\nResults\n\nTable 1 indicates that a vast majority of the participants, accounting for 98.15%, were University of Sharjah (UoS) students residing in various locations, including different emirates in the UAE and overseas. Of these, 96.31% (313 participants) fell within the age range of the study, which was 18 to 24 years. The prevalence of neck pain among UoS students in general was 62.7%, most participants scored above 60 in the NDI (70.46%) (Table 2).\n\n* Location of the student while filling the survey.\n\nAccording to the participants’ responses, the leading causes of neck pain were attributed to incorrect sitting posture and prolonged sitting. Nearly half (47.43%) of the participants experiencing neck pain described it as the worst pain imaginable (Figure 1A). Regarding the pain location, 38.77% identified location A (Figure 1B) at the back of the neck as the primary area, while 32.92% chose location F, representing the right lower trapezius, as the source of pain.\n\nAccording to the Neck Disability Index (NDI) results, a significant majority of participants were able to lift only light weights (60%) (Figure 2A), needed assistance with personal care (85.71%) (Figure 2B), and reported having constant headaches (47.52%) (Figure 2C). Despite feeling slightly anxious due to neck pain (47.51%) (Figure 3A), the participants did not report experiencing depression because of it (50.84%) (Figure 3B).\n\nFurthermore, the findings revealed that 51.00% faced difficulty concentrating on their day-to-day activities (Figure 3C), 54.92% of the participants were unable to work (Figure 4A), and 25.74% managed to drive their vehicle with slight neck pain (Figure 4B). Moreover, the participants reported experiencing disturbed sleep (54.92%) (Figure 5A), difficulty engaging in recreational activities (55.77%) (Figure 5B), and inability to read (51.00%) (Figure 5C). These results demonstrate the gravity of the subjects’ neck pain and its impact on their daily routine and tasks.\n\nRegarding the online learning component, 39.56% of participants reported spending 11 to 20 hours per week on online learning (Figure 6A), with the laptop being the primary device used. The participants’ most common sitting positions (Figure 6B) were position 2 (32%), where they lean forward onto the device, and position 4 (28%), involving arching the neck and not using the chair to support the back. Positions 1, 3, and 5 were selected by 24%, 23%, and 10% of the participants, respectively.\n\nMerely 32.77% of the participants attempted to mitigate their pain through either medication or exercises (7.38% and 6.77%, respectively). The study revealed that neck pain is often dismissed and considered trivial, as evidenced by 91.48% of the participants not seeking medical assistance to alleviate their pain, and of those who did, only 26.14% were prescribed medication.\n\nThe Kruskal-Wallis test results revealed that various lifestyle factors had a substantial impact on the Neck Disability Index (NDI), including lifting, personal care, headaches, anxiousness and depression, work, concentration, sleep, recreational activities, and reading (p>0.005). Notably, driving did not have a significant effect on the NDI score (p=0.186) since most of the participants (58.09%) did not drive. Additionally, participants who did not seek medical attention or receive medical treatment had significant NDI scores (p=0.002).\n\n\nDiscussion\n\nThis study indicates that the prevalence of neck pain among University of Sharjah students during the COVID-19 pandemic-related lockdown period was 62.7%. Of these students, 47.43% experienced neck pain as the worst pain comprehendible. The analysis of the study supports the theory that prolonged sitting for long periods (11-20 hours per week) in front of electronic devices could be a significant cause of neck pain during the unprecedented era of online learning.8,24,25 The prevalence of neck pain among undergraduate students in this study is higher than countries, such as Ethiopia (49.2%),26 India (46.9%),27 Singapore (74%)28 and Taiwan (52%)29 and lower than a study conducted in China (72.9%).30 However, the findings is in accord with a study conducted in Brazil (66.7%),31 Pakistan (69%)32 and Malaysia (65.1%). The observed variability in the prevalence rate of NP across studies could be attributed to disparities in multiple factors, including the geographical setting of the study, the size of the sample population, the methodology employed for sampling, and the assessment instruments utilized.\n\nSeveral studies have established a clear association between the duration of device usage and the occurrence of musculoskeletal pain.33,34 These findings consistently indicate that as the amount of time spent using devices increases, the risk of developing musculoskeletal injuries also rises. In a study by Berolo et al. (2011) 84% of respondents reported pain in various body regions, with the right hand and thumb being the most frequently affected.33\n\nA study conducted in Australia, among the medical undergraduates, showed neck as the most frequently affected region by musculoskeletal pain.35 Likewise, a study in Thailand reported a significant prevalence of neck pain (46%) among undergraduate students, with various risk factors identified as contributors to persistent neck pain.36 Another study by Alzhrani et al. (2019) 80.1% of participants reported musculoskeletal discomfort, with the most commonly affected areas being the neck (64.7%), back (53.8%), and dominant shoulder (38.8%).37 In similar study by Blair et al. (2015,) 67.9% of participants experienced musculoskeletal symptoms with 70.5% reporting discomfort in the neck (86.4%), lower back (75.9%), and right/left shoulders (76.2%).38 Likewise, Olayinka et al. (2013) found that 75.7% of participants reported shoulder complaints.39 Eugenia et al. (2016) also reported that 49.9% of respondents experienced upper limb musculoskeletal symptoms, particularly in the neck and shoulder regions40 which is comparable to the findings of the present investigation, where 38.77% reported back of the neck and 32.92% right lower trapezius. Extended use of electronic devices can lead to “text neck,” characterized by prolonged neck flexion, which can cause inflammation in neck ligaments, muscles, and nerve irritation. If not addressed, this condition can result in permanent arthritic damage and an increased spinal curvature.18 Our findings add to the growing body of research showing that using electronic devices while studying and adopting bad head position can worsen musculoskeletal pain.41\n\nAlso neck pain can significantly disrupt daily activities, potentially hindering individual participation and causing work-related disabilities. Previous reports have conclusively demonstrated the link between neck pain and headaches.42,43 This study also reveals a simultaneous relationship between activities that induce neck pain, unsteadiness, and headaches among university students. The coexistence of neck pain and headache may stem from the compression of the lesser and greater occipital nerves by posterior cervical muscles, with their fascial attachments at the occipital ridge causing local perineural inflammation.44 Furthermore, this study shows a significant correlation between the neck disability index and various lifestyle factors, including lifting, personal care, recreational activities, in addition to symptoms like anxiety and depression. These factors also impacted the students’ ability to work, perform daily chores, and drive.\n\nMaysoun et al. noted that students using electronic devices in Jordan exhibited severe to extremely severe symptoms of stress, anxiety, and depression, along with moderate to severe insomnia.45 A systematic review and meta-analysis comparing the central processing of pain between individuals with non-traumatic neck pain and healthy subjects revealed that symptoms of depression, which are processed at the spinal, cortical, and brainstem levels, manifest as increased sensitivity to pain in the peripheral regions.46\n\nAdditionally, studies from China have indicated that mood disorders are more commonly coexistent with neck pain compared to other mental disorders. Specifically, major depressive disorder exhibited a notably higher association with neck pain than other mood-related conditions.47 This suggests the possibility that the neck pain reported by participants in this study might be linked to mental disorders that emerged during the COVID-19 period.\n\nThe rising prevalence of musculoskeletal pain, particularly neck pain among students, calls for urgent preventive measures and proper guidance on posture.\n\nImproper postures like sitting with crossed legs, hunching while walking, and forward neck leaning with rounded shoulders not only lead to neck and shoulder discomfort but can also cause imbalanced spinal pressure, possibly resulting in persistent lower back pain.48,49\n\nIn the present study, most participants leaned forward onto the device or were arching their neck and not using the chair to support the back while sitting.\n\nEffective strategies like exercise can reduce pain intensity, and educational health programs should inform students about the risks of prolonged computer use, though more research is needed to understand pain development and its contributing factors among undergraduates.\n\nThis study also provides new insight into the importance of implementing more breaks for neck exercises in between class times, scheduling automatic reminders to adjust postures on all online learning platforms, and apply other standard practices done to manage neck pain like proper positioning of the computers and laptops, as it has been reported to be effective in improving neck function and quality of life.50\n\nAdditionally, this study fills in the gaps left by earlier studies that concentrated on either back pain or musculoskeletal pain in general and suggests that future studies concentrate on ergonomic factors like posture and study time, as they believed to be the causes of neck pain according to the students.\n\nThe reliability of this data is limited by recall bias. By determining the prevalence of neck pain among UOS students, this research can attract attention to the importance of postural changes and time spent studying on the severity of neck pain, and the gaps of previously published articles can be filled. To further reduce the morbidity of such avoidable pain, additional preventative interventions and future neck pain research should be conducted with relation to the UAE.\n\n\nEthics approval and consent to participate\n\nThe study protocol was approved by the University of Sharjah research and graduate research ethics committee Reference number: REC-21-02-11-02-S approval date 14.02.2021), in agreement with accepted international standards.\n\n\nConsent for publication\n\nWritten consent was taken for publishing the image of the participant.\n\n\nAuthors’ contribution\n\nConceptualization: Amal Hussein & Anu V Ranade.\n\nData curation: Awab Musaad, Mohamed, Sara Alaaeldin Bashier, Danya Aasim Elkhidir, Mohamad Abdulkafi\n\nFormal analysis: Awab Musaad, Mohamed, Sara Alaaeldin Bashier, Danya Aasim Elkhidir, Mohamad Abdulkafi\n\nInvestigation: Awab Musaad, Mohamed, Sara Alaaeldin Bashier, Danya Aasim Elkhidir, Mohamad Abdulkafi\n\nMethodology: Awab Musaad, Mohamed, Sara Alaaeldin Bashier, Danya Aasim Elkhidir, Mohamad Abdulkafi\n\nProject administration: Awab Musaad, Mohamed, Sara Alaaeldin Bashier, Danya Aasim Elkhidir, Mohamad Abdulkafi\n\nResources: Awab Musaad Mohamed, Sara Alaaeldin Bashier, Anu V Ranade\n\nSupervision: Anu V Ranade & Amal Hussein\n\nSoftware: Awab Musaad Mohamed & Amal Hussein\n\nValidation: Amal Hussein & Anu V Ranade\n\nVisualization: Amal Hussein & Anu V Ranade\n\nWriting – original draft: Awab Musaad, Mohamed, Sara Alaaeldin Bashier, Danya Aasim Elkhidir, Anu V Ranade\n\nWriting – review & editing: Anu V Ranade, Awab Musaad Mohamed, Mohamad Abdulkafi",
"appendix": "Data availability statement\n\nAll data generated and analyzed during this study have been deposited in the Zenodo database.\n\nZenodo: Questionnaire and Data of Neck Pain and Distance learning among university Students During COVID-19, DOI: https://doi.org/10.5281/zenodo.10278960. 51\n\nThis project contains the following underlying data:\n\n1. Excel for charts.xlsx\n\n2. Questionaire.pdf\n\nCreative Commons Attribution 4.0 International\n\n\nAcknowledgment\n\nThe authors extend their gratitude to the participants for their cooperation throughout the study, and to the University of Sharjah for providing the opportunity to conduct this research.\n\n\nReferences\n\nRezai M, et al.: The association between prevalent neck pain and health-related quality of life: a cross-sectional analysis. Eur. Spine J. 2009; 18: 371–381. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSafiri S, 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. Br. Med. J. 2020; 368. Publisher Full Text\n\nHäuser W, et al.: Untying chronic pain: prevalence and societal burden of chronic pain stages in the general population-a cross-sectional survey. BMC Public Health. 2014; 14(1): 1–8. Publisher Full Text\n\nPatel AS, et al.: The impact and burden of chronic pain in the workplace: a qualitative systematic review. Pain Pract. 2012; 12(7): 578–589. PubMed Abstract | Publisher Full Text\n\nCalhoun AH, Ford S, Pruitt AP: Presence of neck pain may delay migraine treatment. Postgrad. Med. 2011; 123(2): 163–168. PubMed Abstract | Publisher Full Text\n\nSung Y-H: Suboccipital Muscles, Forward Head Posture, and Cervicogenic Dizziness. Medicina. 2022; 58(12): 1791. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDighriri YH, et al.: Prevalence and associated factors of neck, shoulder, and low-back pains among medical students at Jazan University, Saudi Arabia: A cross-sectional study. J. Family Med. Prim. Care. 2019; 8(12): 3826–3831. PubMed Abstract | Publisher Full Text\n\nBehera P, et al.: Neck pain among undergraduate medical students in a premier institute of central India: A cross-sectional study of prevalence and associated factors. J. Family Med. Prim. Care. 2020; 9(7): 3574–3581. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHashim R, et al.: Prevalence of Musculoskeletal Symptoms Among Dental Students in United Arab Emirates. BMC Musculoskelet. Disord. 2021; 22(1): 1–5. Publisher Full Text\n\nAl-Ali K, Hashim R: Occupational health problems of dentists in the United Arab Emirates. Int. Dent. J. 2012; 62(1): 52–56. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElshami W, et al.: Prevalence of repetitive stress injuries among radiological technologists in United Arab Emirates. Am. J. Diagn. Imaging. 2018; 3(1): 12–12. Publisher Full Text\n\nNicola M, et al.: The socio-economic implications of the coronavirus pandemic (COVID-19): A review. Int. J. Surg. 2020; 78: 185–193. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeeri NC, et al.: The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned? Int. J. Epidemiol. 2020; 49(3): 717–726. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTadesse S, Muluye W: The impact of COVID-19 pandemic on education system in developing countries: a review. Open J. Soc. Sci. 2020; 08(10): 159–170. Publisher Full Text\n\nAkcil U, Bastas M: Examination of university students’ attitudes towards e-learning during the covid-19 pandemic process and the relationship of digital citizenship. Contemp. Educ. Technol. 2020; 13(1): ep291. Publisher Full Text\n\nHawamdeh M, et al.: Low Back Pain Prevalence among Distance Learning Students. Int. J. Environ. Res. Public Health. 2022; 20(1): 342. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang H, et al.: Association of child mental health with child and family characteristics in rural China: a cross-sectional analysis. Int. J. Environ. Res. Public Health. 2021; 18(10): 5107. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKim H-J, Kim J-S: The relationship between smartphone use and subjective musculoskeletal symptoms and university students. J. Phys. Ther. Sci. 2015; 27(3): 575–579. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlmhdawi KA, et al.: Musculoskeletal pain symptoms among allied health professions’ students: Prevalence rates and associated factors. J. Back Musculoskelet. Rehabil. 2017; 30(6): 1291–1301. PubMed Abstract | Publisher Full Text\n\nHasan MM, et al.: Frequency of musculoskeletal pain and associated factors among undergraduate students. Case Reports in Clinical Medicine. 2018; 07(2): 131–145. Publisher Full Text\n\nAl-Hadidi F, et al.: Association between mobile phone use and neck pain in university students: A cross-sectional study using numeric rating scale for evaluation of neck pain. PLoS One. 2019; 14(5): e0217231. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStefanovitch-Lawbuary N, et al.: Reliability and responsiveness of patient-reported outcome measures of neck disability to physical therapy: comparison of the Copenhagen, Northwick Park, and Neck Bournemouth Questionnaires and the Neck Disability Index. J. Manip. Physiol. Ther. 2019; 42(2): 104–107. PubMed Abstract | Publisher Full Text\n\nJovicic MD, et al.: Validation of the Neck Disability Index in Serbian patients with cervical radiculopathy. J. Manip. Physiol. Ther. 2018; 41(6): 496–502. PubMed Abstract | Publisher Full Text\n\nChan LLY, et al.: The prevalence of neck pain and associated risk factors among undergraduate students: A large-scale cross-sectional study. Int. J. Ind. Ergon. 2020; 76: 102934. Publisher Full Text\n\nAyhualem S, et al.: Burden of neck pain and associated factors among smart phone user students in University of Gondar, Ethiopia. PLos One. 2021; 16(9): e0256794. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWeleslassie GG, et al.: Burden of neck pain among medical students in Ethiopia. BMC Musculoskelet. Disord. 2020; 21(1): 1–9.\n\nAhmed S, et al.: Prevalence of text neck syndrome and SMS thumb among smartphone users in college-going students: a cross-sectional survey study. J. Public Health. 2021; 29: 411–416. Publisher Full Text\n\nToh SH, et al.: A prospective longitudinal study of mobile touch screen device use and musculoskeletal symptoms and visual health in adolescents. Appl. Ergon. 2020; 85: 103028. PubMed Abstract | Publisher Full Text\n\nYang S-Y, et al.: Association between smartphone use and musculoskeletal discomfort in adolescent students. J. Community Health. 2017; 42: 423–430. PubMed Abstract | Publisher Full Text\n\nAlZarea BK, Patil SR: Mobile phone head and neck pain syndrome: proposal of a new entity. Headache. 2015; 251: 63.\n\nDe Vitta A, et al.: Neck pain and factors associated in University Students: a cross sectional study. Ciência em Movimento. 2020; 22(43): 89–101. Publisher Full Text\n\nSachdev S, et al.: Prevalence of neck pain among the undergraduate physical therapy students of university of Balochistan, Quetta, Pakistan. J. Nov. Physiother. Rehabil. 2021; 8: 20–23.\n\nBerolo S, Wells RP, Amick BC III: Musculoskeletal symptoms among mobile hand-held device users and their relationship to device use: a preliminary study in a Canadian university population. Appl. Ergon. 2011; 42(2): 371–378. PubMed Abstract | Publisher Full Text\n\nBalakrishnan R, Chinnavan E, Feii T: An extensive usage of hand held devices will lead to musculoskeletal disorder of upper extremity among student in AMU: A survey method. Int. J. Phys. Educ. Sports Health. 2016; 3(2): 368–372.\n\nSmith D, Leggat P: Prevalence and distribution of musculoskeletal pain among Australian medical students. J. Musculoskelet. Pain. 2007; 15(4): 39–46. Publisher Full Text\n\nKanchanomai S, et al.: Risk factors for the onset and persistence of neck pain in undergraduate students: 1-year prospective cohort study. BMC Public Health. 2011; 11(1): 1–8. Publisher Full Text\n\nAlzhrani A, et al.: Handheld mobile devices—how do we use them at work? A university case study. in Proceedings of the 20th Congress of the International Ergonomics Association (IEA 2018) Volume III: Musculoskeletal Disorders 20. Springer; 2019.\n\nBlair B, Gama M, Toberman M: Prevalence and risk factors for neck and shoulder musculoskeletal symptoms in users of touch-screen tablet computers.2015. Reference Source\n\nObembe AO, et al.: Musculoskeletal pain among undergraduate laptop users in a Nigerian University. J. Back Musculoskelet. Rehabil. 2013; 26(4): 389–395. PubMed Abstract | Publisher Full Text\n\nWoo EH, White P, Lai CW: Musculoskeletal impact of the use of various types of electronic devices on university students in Hong Kong: An evaluation by means of self-reported questionnaire. Man. Ther. 2016; 26: 47–53. PubMed Abstract | Publisher Full Text\n\nSmith L, et al.: Prevalence of neck pain and headaches: impact of computer use and other associative factors. Cephalalgia. 2009; 29(2): 250–257. PubMed Abstract | Publisher Full Text\n\nBlaschek A, et al.: Self-reported muscle pain in adolescents with migraine and tension-type headache. Cephalalgia. 2012; 32(3): 241–249. PubMed Abstract | Publisher Full Text\n\nUthaikhup S, et al.: Effectiveness of physiotherapy for seniors with recurrent headaches associated with neck pain and dysfunction: a randomized controlled trial. Spine J. 2017; 17(1): 46–55. PubMed Abstract | Publisher Full Text\n\nBlake P, Burstein R: Emerging evidence of occipital nerve compression in unremitting head and neck pain. J. Headache Pain. 2019; 20(1): 1–7. Publisher Full Text\n\nAtoum M, et al.: Electronic Devices Use Association with Psychological Distress and Sleep among Adolescents. Electron. J. Gen. Med. 2021; 18(6). Publisher Full Text\n\nXie Y, et al.: Comparing central pain processing in individuals with non-traumatic neck pain and healthy individuals: a systematic review and meta-analysis. J. Pain. 2020; 21(11-12): 1101–1124. PubMed Abstract | Publisher Full Text\n\nXu Y, et al.: The comorbidity of mental and physical disorders with self-reported chronic back or neck pain: Results from the China Mental Health Survey. J. Affect. Disord. 2020; 260: 334–341. PubMed Abstract | Publisher Full Text\n\nSchwertner DS, et al.: Young people’s low back pain and awareness of postural habits: A cross-sectional study. J. Back Musculoskelet. Rehabil. 2022; 35(5): 983–992. PubMed Abstract | Publisher Full Text\n\nMartin PE, Nelson RC: The effect of carried loads on the walking patterns of men and women. Ergonomics. 1986; 29(10): 1191–1202. PubMed Abstract | Publisher Full Text\n\nTunwattanapong P, Kongkasuwan R, Kuptniratsaikul V: The effectiveness of a neck and shoulder stretching exercise program among office workers with neck pain: a randomized controlled trial. Clin. Rehabil. 2016; 30(1): 64–72. PubMed Abstract | Publisher Full Text\n\nRanade A: Questionnaire and Data of Neck Pain and Distance learning among university Students During COVID-19. [Data set]. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "275293",
"date": "25 May 2024",
"name": "B.V. Murlimanju",
"expertise": [
"Reviewer Expertise Morphology",
"Clinical Anatomy",
"Neurosurgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript is very interesting and offers a novel information to the scientific community. I could suggest only few changes. 1. The subheadings in the background/introduction could be removed. 2. The recent articles about the ergonomics of a university students can be cited. 3. Any details of the doctors consultation, radiographs, MRI neck taken, usage of cervical collar can be added in the results section. 4. If not advised/used, this can be mentioned. 5. The comparison between male and female need to be added. 6. The conclusion section to be included. This can be a reflection of the objectives.\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? No",
"responses": [
{
"c_id": "12695",
"date": "08 Nov 2024",
"name": "Anu V",
"role": "Author Response",
"response": "Reviewers comment: The subheadings in the background/introduction could be removed. Our response: Removed as suggested .Reviewers comment: The recent articles about the ergonomics of a university students can be cited. Our response: Articles related to ergonomics of a university students are included in the manuscript as per the reviewer’s suggestion. (Enhancing student awareness of postural changes and risk factors, coupled with the implementation of ergonomic practices, can significantly mitigate musculoskeletal symptoms, including neck pain (Kilroy, et al., 2000; Bansode et al., 2016; Naik Prashant et al., 2017)). Reviewers comment: Any details of the doctor’s consultation, radiographs, MRI neck taken, usage of cervical collar can be added in the results section. If not advised/used, this can be mentioned. Our response: Mentioned in the manuscript as suggested (Since the study did not include information regarding the doctor's consultation, radiographs, MRI neck, or the use of a cervical collar, we have incorporated the same in the results section. Reviewers comment: The comparison between male and female needs to be added. Our response: Thank you for raising this important comment. We agree that a comparison between male and female students would have been necessary to investigate whether sex is a factor associated with the prevalence of neck pain and/or its intensity. Yet, as related to the context of this study, knowing that the majority of the student population at the University of Sharjah, from which the study sample was selected, includes females, thus the variation concerning sex distribution is minimal. Sex was not among the measured variables and therefore, conducting this comparison will not be possible at this point due to data anonymity. In response to the reviewer's comment, we have added a statement under the study limitations to reflect this gap. (Limitations: This study is subject to several limitations. Firstly, self-selection bias may have influenced the results, as individuals with neck pain may be more likely to participate in an online survey than those without symptoms. This could potentially contribute to the observed high prevalence of neck pain in the study population. Secondly, the targeted recruitment of University of Sharjah students, friends, and colleagues may have introduced response bias. Lastly, in this study, comparing the prevalence of neck pain between male and female students was not done due to the lack of sufficient diversity in the study population with respect to sex distribution. Therefore, we recommend future research to investigate this association.) Reviewers comment: The conclusion section to be included. This can be a reflection of the objectives. Our response: Included in the manuscript as suggested (This study highlights the significant prevalence of neck pain among University of Sharjah students during the COVID-19 pandemic. Prolonged electronic device use and poor posture were identified as primary causes. The findings underscore the need for preventive measures, including promoting proper posture, encouraging regular breaks, and providing educational resources. Further research is necessary to address this growing health concern.)"
}
]
},
{
"id": "290876",
"date": "04 Jul 2024",
"name": "Tomas Nakazato",
"expertise": [
"Reviewer Expertise Physical Medicine and Rehabilitation. Musculoskeletal Pain."
],
"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 objective of the study is remarkably interesting and worthy, and I appreciate the effort the authors have put into this work; however, I have several observations and found many fundamental flaws.\nAmong the several observations and shortcomings, I would like to highlight some of the most noticeable ones for me.\nINTRODUCTION\nAuthors do not use abbreviations as customary. For example, neck pain may be NC, to avoid repetition and to improve clarity and conciseness of the paper. Some paragraphs are very short; they could be merged for better redaction. Many references discuss musculoskeletal pain in general, rather than specifically focusing on neck pain (Ref. 9, 10, 11, 16, 17, 18, 19, 20), and not related to university students or the young population.\nMETHODS.\nThe study aims to measure the prevalence of neck pain among University of Sharjah (UOS) students during the online learning period for the COVID-19 pandemics and to investigate the factors that caused it. In our opinion, the method to obtain the prevalence was not appropriate, since the authors used a questionnaire posted online on different platforms (Facebook, WhatsApp, Instagram, and “others”). We do not know if the 'others' social media platforms are reliable to collect information. As participants were volunteers, we consider that people with neck pain were more likely to participate than healthy individuals, increasing the sampling bias of neck pain conditions. As researchers called their close friends and colleagues to participate, it may increase the response bias of the study. There is no definition of 'neck pain': the main variable. There is a huge difference between acute and chronic neck pain, neck pain that radiates to the upper limb, neck pain that radiates to the head, etc. Acute neck pain usually resolves spontaneously and does not condition disability in most cases. Radiculopathic neck pain is very different from non-specific neck pain, and so on. The target population was first defined as UoS students aged 18-24. Then, the inclusion criteria comprised all UoS students aged 17-24 studying at the Sharjah campus. Subsequently, in the results authors accounted that 98.15% were UoS students (so 1.85% were not UoS students? And if that was the case, why did the authors include these data?). The authors used a self-administered questionnaire. The problem we see is that it consisted of a \"modified\" Neck Disability Index (NDI), adding additional questions to explore other factors associated with neck pain. We should be very careful if we modify standardized instruments to collect information. We do not know whether this modified NDI was validated. Furthermore, we do not know if it was administered in English or the official language of the UAE. There is a reference (23) on the validation of the Neck Disability Index in Serbian patients and another on the comparison of the NDI vs. other pain questionnaires (22), both of which do not clarify our doubts. These may result in improper answers from participants. In the questionnaire, the authors try to explore the effects of neck pain on the anxiousness and depression of participants. In our opinion, we do not agree to explore complex conditions such as anxiousness and depression with two simple questions. If self-reported, these conditions should be explored with standardized questionnaires evaluating different aspects to conclude if the participant has some degree of anxiousness, anxiety and/or depression in the survey. We checked the drawing to detect the location of the pain in the original questionnaire, which was different from that presented in the manuscript. In our view, the original drawing was not suitable for the appropriate location of neck pain by the participants.\nRESULTS\nFor the reasons mentioned above, we have doubts about many of the results presented in this study. For example, it is very difficult for us to accept that nearly half of the participants experienced neck pain described as the 'worst pain imaginable' (47.43%), more than half of the participants ´could not concentrate at all´ (51.80%) or had 'completely disturbed sleep' (54.92%). These results mean that half of the students were unable to study or even function at all, which seems unrealistic to us. Furthermore, with that level of pain and disability reported, in our opinion, it is not conceivable that 91.48% of participants did not seek medical assistance (most individuals with that level of compromise should have sought at least an online medical consultation, according to our clinical practice). In addition, using the same logic, it is inconceivable that only 32.77% of cases tried to alleviate their pain. “The Kruskal-Wallis test results revealed that various lifestyle factors had a substantial impact on the Neck Disability Index (NDI), including lifting, personal care, headaches, anxiousness and depression, work, concentration, sleep, recreational activities, and reading”. To our knowledge, NDI does not measure anxiousness or depression. This modification was apparently made by the authors and should have been shown separately. We believe that the figures are not presented properly. For example, we do not understand the criterion why Figures 2, 3, 4, and 5 are grouped separately with pie charts named A, B, and C. If results are part of a standardized questionnaire (NDI Score), graphics from this source of data should be presented as a whole (an individual figure with pie charts).\nDISCUSSION\nDiscussion does not highlight the (several) limitations of the study. The only limitation presented was the recall bias. The comparison of the prevalence of neck pain in this study with other countries is inaccurately presented. Same observation as in the Introduction: Some paragraphs are short; they could be merged for better redaction.\nCONCLUSION\nThe conclusion does not reflect the results of the study, but rather contains comments or opinions from the authors.\nStatistical analysis and its interpretation: Based on numerous observations, we deemed a review of statistical analysis and interpretation unnecessary at this time.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": []
},
{
"id": "290872",
"date": "22 Jul 2024",
"name": "Fairus Fariza Zainudin",
"expertise": [
"Reviewer Expertise injury pattern and profiling",
"sports rehabilitation",
"musculoskeletal pain",
"sports concussion",
"Cardiopulmonary resuscitation education."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nTitle: It concisely captures the main focus of the study, using appropriate scientific terminology.\nAbstract: \"Include ethical approval details, participant demographics (age, gender distribution, and faculty representation), and specify whether participants were athletes or non-athletes. Report the mean and standard deviation of NDI scores, both overall and stratified by age groups. Provide information on neck pain severity using validated scales (e.g., VAS or NRS). Briefly describe the methodology for assessing factors affecting neck pain, including questionnaire design. Clarify the NDI scoring system, as the current abstract reports values that exceed 100% (83.89 vs 125.80, p=0.002). In the conclusion, justify the focus on the UAE and articulate the practical implications of this research.\"\nResults: \"Address the inclusion of participants under 18 (n=10) and over 24 (n=2) years of age, as these fall outside the stated inclusion criteria. Consider removing these data points and reassessing the findings. Given the established pattern of increasing neck pain prevalence, consider adopting a more stringent significance level (p < 0.025). Provide a detailed explanation of the NDI scoring system and severity classification, citing relevant normative data. Elucidate the process for selecting neck pain-related factors during the pandemic. Report the results of pilot testing and tester reliability. In Table 2, include mean and standard deviation for NDI scores.\"\nDiscussion: \"Revise the statement on 'rising prevalence' to reflect the cross-sectional nature of this study, acknowledging that trend analysis would require longitudinal data from multiple institutions. Elaborate on the biomechanical and ergonomic factors contributing to prolonged poor posture among students. Reconsider the phrase 'new insight' regarding the importance of breaks for neck exercises, as this is a well-established principle in ergonomics and occupational health. Deepen the discussion by incorporating physiological, behavioral, biomechanical, and psychological perspectives when comparing results to existing literature. Enhance the practical implications section to provide clear, actionable recommendations based on the study 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? 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": "12696",
"date": "08 Nov 2024",
"name": "Anu V",
"role": "Author Response",
"response": "Abstract: Reviewers comment: \"Include ethical approval details, participant demographics (age, gender distribution, and faculty representation), and specify whether participants were athletes or non-athletes. Response: Included in the manuscript as suggested. (This cross-sectional study used an online survey distributed to University of Sharjah students via social media from February 16 to March 12, 2021, following ethical approval. The study participants were young adults aged 18 to 26. Due to the predominantly female demographic of the university student population and pandemic-related restrictions, gender and athletic status were not considered significant variables in this research.) Reviewers comment: Report the mean and standard deviation of NDI scores, both overall and stratified by age groups. Response: Included in the manuscript as suggested (\"Participants who did not seek medical attention had significantly higher levels of neck pain disability, as measured by the NDI. The median NDI score for those who did not seek treatment was 20, with an interquartile range of 16.89. In contrast, the median NDI score for those who did seek medical attention was 34.00, with an interquartile range of 22.\") Reviewers comment: Provide information on neck pain severity using validated scales (e.g., VAS or NRS). Briefly describe the methodology for assessing factors affecting neck pain, including questionnaire design. Response: Since our objective was to identify factors that are associated with the intensity of the neck pain rather than the intensity itself. The question in the questionnaire was added to get a subjective view of how participants express their neck pain intensity. Reviewers comment: Clarify the NDI scoring system, as the current abstract reports values that exceed 100% (83.89 vs 125.80, p=0.002). In conclusion, justify the focus on the UAE and articulate the practical implications of this research. Response: Thank you for bringing this to our notice. The mean rank was reported by mistake. Since the data is skewed in this question, the median and interquartile range were added. Justifications were added to the conclusion as requested. Results: Reviewers comment: \"Address the inclusion of participants under 18 (n=10) and over 24 (n=2) years of age, as these fall outside the stated inclusion criteria. Consider removing these data points and reassessing the findings. Given the established pattern of increasing neck pain prevalence, consider adopting a more stringent significance level (p < 0.025). Provide a detailed explanation of the NDI scoring system and severity classification, citing relevant normative data. Elucidate the process for selecting neck pain-related factors during the pandemic. Report the results of pilot testing and tester reliability. Response: Included as suggested. (NDI scores were found to be skewed. The median is 16% which indicates mild neck pain. The interquartile range is 19.11. Participants who did not seek medical attention had significantly higher levels of neck pain disability, as measured by the NDI. The median NDI score for those who did not seek treatment was 20, with an interquartile range of 16.89. In contrast, the median NDI score for those who did seek medical attention was 34.00, with an interquartile range of 22). Reviewers comment: In Table 2, include mean and standard deviation for NDI scores. Response: As stated earlier, the NDI scores were found to be skewed. The median and interquartile range were added to table 2. Discussion: Reviewers comment: \"Revise the statement on 'rising prevalence' to reflect the cross-sectional nature of this study, acknowledging that trend analysis would require longitudinal data from multiple institutions. Our response: Modified as in the manuscript as suggested (The observed prevalence of musculoskeletal pain, particularly neck pain, among students in this cross-sectional study necessitates further investigation. Longitudinal data from multiple institutions are essential to establish definitive trends and inform comprehensive interventions.) Reviewers comment: Elaborate on the biomechanical and ergonomic factors contributing to prolonged poor posture among students. Reconsider the phrase 'new insight' regarding the importance of breaks for neck exercises, as this is a well-established principle in ergonomics and occupational health. Our response: Modified in the manuscript as suggested (The excessive use of electronic devices can lead to \"text neck,\" a condition characterized by chronic neck flexion. This can result in inflammation of the neck's ligaments, muscles, and nerves, potentially leading to long-term consequences such as permanent arthritic damage and an increased spinal curvature. Biomechanical factors, such as repetitive strain on neck muscles from prolonged forward head posture (Goodarzi et al., 2018), and ergonomic factors, such as the use of poorly designed furniture and inadequate lighting (Eldho & Muthukumar, 2022; Meshram et al., 2021; Brewer, 2006), can contribute to poor posture and exacerbate the development of text neck. These combined factors can increase the risk of musculoskeletal pain and discomfort among students. While the efficacy of incorporating neck exercise breaks is well-established in ergonomics and occupational health literature, this study further underscores its significance in mitigating the negative effects of prolonged sedentary behavior on student health. In addition to regular breaks, implementing strategies such as scheduling automatic reminders to adjust posture on online learning platforms and adopting proper computer and laptop positioning can significantly enhance neck function and quality of life. [50]. These interventions, when combined with neck exercises, can effectively alleviate NP and discomfort among students.) Reviewers comment: Deepen the discussion by incorporating physiological, behavioral, biomechanical, and psychological perspectives when comparing results to existing literature. Enhance the practical implications section to provide clear, actionable recommendations based on the study findings.\" Our response: Incorporated in the manuscript as suggested. (The development of NP is influenced by a multifaceted interplay of factors. Demographic factors, such as age, gender, height, and weight, can predispose individuals to NP. Biomechanical factors, including forceful exertions, repetitive movements, and awkward postures, can exacerbate existing conditions or contribute to the development of new ones. Psychosocial factors, such as job stress, work dissatisfaction, and poor ergonomic practices, and behavioral factors, such as tobacco use, alcohol consumption, physical activity levels, stress management, and sleep hygiene, can all contribute to the risk of NP (McLean SM et al., 2010). Additionally, environmental factors, such as the physical layout of a workplace or the nature of tasks performed, can influence the likelihood of its occurrence (Kanchanomai et al., 2011; Razvi et al., 2018; Kalirathinam et al., 2017; Lee et al., 2018).Biomechanical factors, such as repetitive strain on neck muscles from prolonged forward head posture (Goodarzi et al., 2018), and ergonomic factors, such as the use of poorly designed furniture and inadequate lighting (Eldho & Muthukumar, 2022; Meshram et al., 2021; Brewer, 2006), can contribute to poor posture and exacerbate the development of text neck. These combined factors can increase the risk of musculoskeletal pain and discomfort among students. University students frequently experience significant perceived stress, particularly in the form of academic stressors. These stressors can include academic demands, financial concerns, time pressures, health issues, and self-imposed pressures (Pamela, L. 2009). Studies have linked high levels of mental stress among students to an increased risk of musculoskeletal disorders, such as low-back pain and neck pain (Lundberg U, et al., 2002). Additionally, research has demonstrated that time pressure can increase the activity of various muscles, potentially leading to increased biomechanical load and musculoskeletal disorders. For example, studies have shown that time pressure can increase the activity of the trapezius, infraspinatus, deltoid, and extensor digitorum muscles (Birch et al., 2003), which can contribute to strain and discomfort in the neck, shoulders, and upper back. Conclusion: This study underscores the prevalence of NP among University of Sharjah students during the COVID-19 pandemic. Prolonged electronic device use and poor posture were identified as primary contributors. Given the limited local research in this area, the study focused on the United Arab Emirates. The findings highlight the necessity for implementing preventive measures, raising awareness, and establishing regulations to mitigate the adverse health effects of distance learning. These measures should include promoting proper posture, encouraging regular breaks, and providing educational resources. Further research is imperative to address this emerging health concern.)"
}
]
}
] | 1
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https://f1000research.com/articles/13-307
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https://f1000research.com/articles/9-1224/v1
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12 Oct 20
|
{
"type": "Software Tool Article",
"title": "BioSounds: an open-source, online platform for ecoacoustics",
"authors": [
"Kevin F.A. Darras",
"Noemí Pérez",
"Mauladi -",
"Tara Hanf-Dressler",
"Mauladi -",
"Tara Hanf-Dressler"
],
"abstract": "Passive acoustic monitoring of soundscapes and biodiversity produces vast amounts of audio recordings. However, the management of these raw data presents technical challenges and their analysis suffers from bottlenecks. A multitude of software solutions exist, but none can perform all the data processing needed by ecologists for analysing large acoustic data sets. The field of ecoacoustics needs a software tool that is free, evolving, and accessible. We take a step in that direction and present BioSounds: an open-source, online platform for ecoacoustics designed by ecologists and built by software engineers. Biosounds can be used for archiving and sharing recordings, manually creating and reviewing annotations of sonant animals in soundscapes, analysing audio in time and frequency, and storing reference recordings for different taxa. We present its features and structure, and compare it with similar software. We describe its operation mode and the workflow for typical use cases such as the analysis of bird and bat communities sampled in soundscape recordings. BioSounds is available from: https://github.com/nperezg/biosounds",
"keywords": [
"Soundscape",
"sound analysis",
"ecoacoustics",
"passive acoustic monitoring",
"automated sound recording",
"autonomous recording units",
"spectrogram",
"audio annotation"
],
"content": "Introduction\n\nAutomated, passive recording for biodiversity research has come of age. It presents new opportunities for ecologists, but yields huge amounts of data that are challenging to manage1. The resulting recordings are raw data that require considerable effort to extract the ecological information contained within. To realise the potential of ecoacoustics projects, different software tools are required in different data processing and analysis stages: First, soundscape recordings - comprising all sounds recorded in a landscape2 - need to be archived and made accessible to collaborators, either locally or remotely3. Sometimes, an optional pre-processing stage (e.g., re-sampling, merging and splitting, compressing of recordings) is conducted using audio editing software4. In general, recordings need to be visualized using spectrograms (i.e., sonograms) and played back to detect, identify, and then manually annotate the target sounds (usually sonant animal species)4,5. To our knowledge, no dedicated tool allows for a consistent, structured validation workflow of these manual annotations yet by independent experts. Increasingly, automated detection and classification of sounds is used to facilitate processing large amounts of audio data6. The latter still need to be verified by human experts, who rely either on their own knowledge, or reference recordings found in audio repositories (i.e., reference sound libraries) linking recordings to species identities7. Alternatively to their time-consuming manual annotation, soundscapes can be characterised with automatically computed eco-acoustic indices that can be linked to biodiversity metrics8,9, or with general acoustic feature sets that can be used to detect anomalous sound events in an unsupervised manner10. Finally, in bioacoustics- or behavior-focused studies, but also for the identification of bats, the target sounds need to be analysed further by measuring their properties in the frequency-time-amplitude space11,12. At the time of writing, no software integrates all these different data processing stages into a consistent, integrated workflow, and reference libraries are still scarce for particular species groups1.\n\nSoftware tools that handle audio data need to be built sustainably to benefit a large user base in the research community. While the majority of software is free, few are online-based, many are specialised on specific taxa, and only half of them are open-source (Table 1). It is essential to have free tools that all researchers and practitioners can use, irrespective of their budget constraints. Also, only open-source projects guarantee that they can be continuously developed to keep up with the pace of technological progress, that they stay accessible over time, and that the actual functions are transparent and replicable. Within two years, three out of the 19 reported software tools by Priyadarshani et al.6 appear to have ceased development. Accessibility, which is essential for international collaboration and verification of bioacoustic data13, also requires online solutions that are mostly independent of operating systems or any commercial software. In a nutshell, the field of ecoacoustics requires an open-source, online tool, as this fulfils most requirements: being free, easily maintainable, collaborative and accessible.\n\nWe included only ecoacoustics software tools built specifically for ecoacoustics that can play back audio and represent audio visually in the form of spectrograms. We excluded tools that were not developed in the last 2 years.\n\nWe present BioSounds: an open-source, online platform for ecoacoustics, designed by ecologists and built by software engineers. Currently, BioSounds can be used to manage soundscape and reference recording collections, to manually create and independently review annotations in recordings, and to perform basic sound measurements in time and frequency. BioSounds was originally based on Pumilio3 but the latter has ceased development and Biosounds has considerably expanded since. At the moment of writing, only one other software - Ecosounds - offers similar functions as BioSounds5, and we compare them with each other (Table 2). We detail the structure and functionality of BioSounds in the following and announce our development goals.\n\nWe compared both software tools’ functionalities that are relevant for administrators and normal users. Both tools work with Chrome, Firefox, and Internet Explorer browsers.\n\n\nMethods\n\nCoding languages, libraries, and tools. BioSounds is a web-based application written in PHP 714, Python 2.715, Javascript16, JQuery 3.417, Twig 218, CSS19 and HTML 520. It uses Web Audio API21, Sox 14.422, Lame23 and ImageMagick24 software for sound and image processing, a MySQL25 database for organising the data (Figure 1), a RabbitMQ26 queue for file processing, Plupload 1.5 as a visual file upload tool27, JQuery UI 1.1228, JCrop 0.929, Bootstrap 4.330 and the Symfony 4 process component31 for managing the scripts execution. The Python libraries used are: Numpy32, Pillow33 and Audiolab 0.834. We containerized the project using Docker35, which spares software developers the time for installing libraries, the database, and configuring the server. This setup allows developers to run the project on their machines quickly and free of typical installation issues like library version incompatibilities.\n\nAudio visualization and playback. The core sound visualisation and playback tasks are handled by two distinct components. First, spectrogram images are generated by the Python script ‘sound visualization tool’, which was created for the discontinued ‘Pumilio’ project3. This script generates spectrograms by computing a Fast-Fourier Transform on the waveform of the audio recording. Second, sound playback and speed control use Web Audio API, a high-level application programming interface for processing and synthesizing audio in web applications. It is included in modern browsers to take advantage of the browser resources without requiring any extra media player or library in our project, and we plan to use it for generating spectrograms too.\n\nServer installation. BioSounds is published in a GitHub repository36 and needs to be installed in a web server to run. Instructions and general information regarding the setup for developers and the production server are included in the README file on GitHub. The BioSounds installation for local development (in the developer’s machine) is facilitated by a Docker setup. We provide a set of Docker configuration files that can also aid the server installation, but the final setup should be carried out by the server administrator (or devOps engineer) of the institution. For server installations without Docker, a step-by-step installation guide is provided in the repository.\n\nAccess. We run an online instance of BioSounds for our project SoundEFForTS37, where most of the steps described in the use cases below can be reproduced. This website can host public reference collections (i.e., reference audio libraries) for prospective users, for instance for Chiroptera and Anura. Soundscape collections, due to their larger size, can be integrated up to a manageable size for projects contributing to BioSounds development.\n\nUsers can access BioSounds (both the existing instance and future installations) via a desktop browser with an internet connection. BioSounds works with Windows, Linux, and MacOS operating systems and the most common internet browsers (Firefox, Chrome, Safari).\n\nCollections. BioSounds organises audio recordings (named “recordings” hereafter) within collections. Collections can be accessed through the \"Collections\" drop-down menu. Those that are part of ongoing research projects are only visible to registered users; open collections are public. Collection creation is still handled directly via the database by adding it to the table ´Collection´. Administrators can then upload recordings in most common audio formats into collections. PNG image previews of the spectrograms and MP3s of the audio file are generated after insertion into the database. Audio recordings can be given names that differ from the default file name. Collections can be shown with a gallery view (thumbnails with sound names) or a list view with larger spectrograms and a simple audio player, and comments can be inserted. There are two types of collections in BioSounds: soundscape recording collections (\"soundscape collections\" hereafter) and reference recording collections (i.e., reference audio libraries; named \"reference collections\" hereafter).\n\nSoundscape collections contain field recordings which each encompass a range of sounds from a particular site during a particular time interval. The recordings within are displayed with the gallery view by default, which shows either mono or stereo thumbnails of their spectrograms along with the sound names and the overlaid maximum recorded sound frequency (Figure 2).\n\nReference recording collections link individual recordings to identified sound sources (typically, sonant animal species). They display recordings with a list view by default; an example is shown in the public “Reference collection Anura”. Reference collections can host recordings that are needed for supporting the identification of the animals of particular taxa or regions. The spectrogram in the list view gives a rapid overview of the reference sound, and the embedded audio player can play it back directly (Figure 3). In contrast to soundscape recordings, uploaded reference recordings need to be assigned to animal species, and they can have a vocalisation type and quality rating. Reference collections can be filtered by species and rating.\n\nReference collections can be filtered by species and rating, and additional information regarding the recording is displayed. Reference recordings can be played back directly in list view.\n\nUsers. BioSounds has two registered user classes: normal users and administrators. All registered users can open all recordings inside the spectrogram player, as well as create, view, and edit their own annotations (called \"tags\" in BioSounds) that are linked to sound sources (mostly sonant animal species). Normal users have viewing and reviewing privileges for other users' tags that are set by administrators for single collections. Administrators can view, review, and edit all users' tags. They can also create users, set their tags' color, and define their status (normal user/administrator). Finally, administrators can upload, rename, and delete recordings.\n\nSpectrogram player. Recordings can be opened in the spectrogram player (Figure 4). Spectrograms are visualisations of sound where sound amplitude is shown in color or grayscale tones, time is shown on the X axis, and frequency is displayed on the Y axis. The spectrogram player offers various functionalities for tagging sounds: it is possible to play back sound, filter frequencies, navigate the spectrogram, assign selections to animal species (or other sound sources), and perform basic sound analysis.\n\n1: sound and collection name. 2: annotating/tagging sounds. 3: hiding/showing tags. 4: playback mode. 5: moving window left and right. 6: audio channel selection. 7: overview spectrogram, red rectangle shows current view. 8: playback speed. 9: playback/pause and stop, time position. 10: playback cursor. 11: time (s) and frequency (Hz) coordinates of current view or selection. 12: copying time and frequency coordinates. 13: zooming. 14: continuous playback. 15: frequency filter. 16: utilities: image and audio download, file info. 17: tags of different users shown with different colors. 18: reviewed tags with solid border. 19: not yet reviewed tags with dashed border. 20: tags without detection distance with orange shading. 21: tag species appears on click, with buttons for editing, zooming, and estimating distance.\n\n\nUse cases\n\nSoundscape recordings can be annotated manually and reviewed by expert ornithologists, as exemplified in the collection \"Upland plots dry season 2013\". Users can scan recordings visually and aurally using the built-in reading mode, which zooms to a 60 s long section of the recording, including all frequencies, and enables continuous playback. All avian species can be tagged/annotated based on rectangular spectrogram selections along the frequency and time axes. Species are chosen from the integrated species list, and links to Xeno-canto and Google image searches direct the user to the selected species to support identification (Figure 5). Project-specific reference collections can also be consulted to confirm species identification. Unclear identifications can be marked as uncertain. Coordinates (in time and frequency) are saved automatically based on the boundaries of the selection. Tags can be designated as reference recordings for future inclusion into reference recording collections; comments can be inserted. Tags can be zoomed into and any of the current (filtered or unfiltered) spectrogram views (image or audio) can be downloaded for sharing with collaborators. Distances are estimated in a standardised way using a function that enables full-spectrum viewing and playback of the tags based on a spectrogram of the first 30 s of the tag. Reference audio recordings of test tones emitted at known distances are needed (see recording \"Sound transmission - full spectrum\" in Demo collection) to estimate detection distances in an unbiased way38.\n\nThe right pane is only visible to users with reviewing privileges.\n\nAn advantage of automated acoustic survey data is that they can be validated on multiple levels, yielding accurate datasets39. In BioSounds, it is possible to review tags for validating species identification as well as auxiliary tag data. Administrators can grant tag reviewing privileges to users other than the creator. Users with reviewing privileges can either accept species identifications, revise them by suggesting other species, or reject them by marking the annotation for deletion (Figure 5). Administrators can also check the listening durations of each user for each recording to verify that all recordings have been listened to in entirety, and to extract a measure of the sampling intensity. Finally, it is possible to train users by letting them learn from other users’ annotations after granting them viewing privileges, and thereafter, to test their performance with already annotated recordings where the annotations are invisible to the user being tested. After the validity checks have been run, administrators can export the tag data through a MySQL database administration tool like phpMyAdmin40 for further statistical analysis.\n\nSoundscape recordings that span the ultrasound frequency range (i.e., ultrasoundscapes) can be similarly analysed with the same functions as for the bird community analysis use case, but they present specific challenges regarding the analysis of bat calls. Most importantly, ultrasound is not audible, so that users need to use the playback speed slider to reduce the playback frequency to artificially hear the ultrasound calls. This can be tested with the annotated example recording \"Sample Ultrasoundscape\" that is uploaded in the \"Demo\" collection; any playback rate from 0.05 to 1 can be chosen. To aid in bat call visualisation, the spectrogram settings can also be adjusted by administrators to choose different FFT window sizes.\n\nHowever, bat species identification is more challenging as bat calls from different species can be similar. Thus, we included bat morphospecies (to be exact, morphocall types) named with single letters from A to J into the species list, suffixed with digits to designate different call types from the same species. Exact measurement of bat call features (such as start and end frequency, frequency of maximal energy, as well as call and call interval duration) usually determines the assignment bat calls to specific species: using the clipboard button (Figure 4), users can copy the frequency and time coordinates of the current selection to the clipboard to perform basic sound analysis. The exported values can be readily pasted into spreadsheets, and bat call metrics of interest can be rapidly computed with formulae. For those species that have taxonomically unequivocal calls, the users can refer to the reference collection to corroborate their identifications. Finally, manual distance estimation of bat calls is impractical due to their mobility and the fact that we cannot intuitively estimate the distances of human-inaudible sounds, so that the tags can be marked as having not estimable distances.\n\n\nConclusions\n\nBioSounds can be used to archive, visualise, play back, and share soundscape recordings online with users that have different access privileges. The recordings can be analysed collaboratively for detecting sonant animal species such as birds and bats as to derive measures of their activity for use in ecological studies. BioSounds has already been used successfully to analyse bird communities41 and to measure bat activities42, while performing basic sound analysis. Region- and taxon-specific reference collections can be created, like the anuran calls collection we currently host43.\n\nWe strive to expand the functionality of BioSounds and keep it accessible in the long term. Open access is a requirement for future development and maintenance. However, it is not a guarantee for a sustainable project either, as some of the open-source projects listed by Priyadarshani et al. in 20186 are currently discontinued projects. In Biosounds, we refactored the original Pumilio project, implemented best coding practices, and used development tools, like Docker, all of which facilitate developers’ work and help them engage in collaboration. We welcome new collaborators to support the project development who could become co-authors on subsequent versions of this article. Among others, we plan to develop the following functions:\n\nAutomated detection and classification of vocalisations, using existing tools44,45\n\nComputation of acoustic diversity indices to monitor biodiversity46\n\nDeveloping the sound analysis tool to include the sound amplitude dimension\n\nLinking BioSounds to taxonomic databases for an exhaustive, up-to-date list of sonant animals\n\nManaging and displaying geographic locations of recordings3\n\nDisplaying multiple recordings of single sites on a common time axis to visualise longer soundscapes5\n\n\nData availability\n\nAll the recordings referred to here are accessible in open collections without login on our online instance of BioSounds: https://soundefforts.uni-goettingen.de/biosounds/.\n\n\nSoftware availability\n\nSource code available from: https://github.com/nperezg/biosounds\n\nArchived source code at the time of publication: http://doi.org/10.5281/zenodo.404771147.\n\nLicense: GNU General Public License v3.0 (GPLv3).",
"appendix": "Acknowledgements\n\nWe thank the principal investigators of the B09 sub-project of EFForTS Teja Tscharntke and Ingo Grass for their continued support of BioSounds development through student helper funds, as well as colleagues and students who provided feedback.\n\n\nReferences\n\nGibb R, Browning E, Glover-Kapfer P, et al.: Emerging opportunities and challenges for passive acoustics in ecological assessment and monitoring. Methods Ecol Evol. 2018; 10(2): 169–85. Publisher Full Text\n\nPijanowski BC, Villanueva-Rivera LJ, Dumyahn SL, et al.: Soundscape Ecology: The Science of Sound in the Landscape. BioScience. 2011; 61(3): 203–16. Publisher Full Text\n\nVillanueva-Rivera LJ, Pijanowski BC: Pumilio: a web-based management system for ecological recordings. Bull Ecol Soc Am. 2012; 93(1): 71–81. Publisher Full Text\n\nAudacity Team: Audacity(R): Free Audio Editor and Recorder. 2018.\n\nQUT Ecoacoustics Research Group: EcoSounds. GitHub. [cited 2019 Dec 19]. Reference Source\n\nPriyadarshani N, Marsland S, Castro I: Automated birdsong recognition in complex acoustic environments: a review. J Avian Biol. 2018; 49(5): jav-01447. Publisher Full Text\n\nXeno-canto Foundation: Xeno-canto: Sharing bird sounds from around the world. Xeno-canto Foundation Amsterdam; 2012.\n\nSueur J, Farina A, Gasc A, et al.: Acoustic Indices for Biodiversity Assessment and Landscape Investigation. Acta Acust United Acust. 2014; 100(4): 772–81. Publisher Full Text\n\nSueur J, Aubin T, Simonis C: Equipment Review-Seewave, A Free Modular Tool for Sound Analysis and Synthesis. Bioacoustics. 2008; 18(2): 213. Reference Source\n\nSethi SS, Jones NS, Fulcher BD, et al.: Characterizing soundscapes across diverse ecosystems using a universal acoustic feature set. Proc Natl Acad Sci U S A. 2020 [cited 2020 Jul 8]; 117(29): 17049–17055. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThe Cornell Lab - Center for Conservation Bioacoustics. Raven Pro.\n\nObrist MK, Boesch R: BatScope manages acoustic recordings, analyses calls, and classifies bat species automatically. CJZ Virtual Spec Issues. 2018; 96(9): 939–54. Publisher Full Text\n\nGaunt SLL, Nelson DA, Dantzker MS, et al.: New Directions for Bioacoustics Collections. The Auk. 2005; 122(3): 984–7. Publisher Full Text\n\nPHP: Hypertext Preprocessor. [cited 2020 Aug 24]. Reference Source\n\nPython Programming Language. Python.org. [cited 2020 Aug 24]. Reference Source\n\nJavaScript. MDN Web Docs. [cited 2020 Aug 24]. Reference Source\n\njs.foundation JF-. jQuery: Javascript library. [cited 2020 Aug 24]. Reference Source\n\nTwig - PHP template engine.. Home - Twig - The flexible, fast, and secure PHP template engine, [cited 2020 Aug 24]. Reference Source\n\nCSS: Cascading Style Sheets. MDN Web Docs. [cited 2020 Aug 24]. Reference Source\n\nHTML5. MDN Web Docs. [cited 2020 Aug 24]. Reference Source\n\nWeb Audio API. MDN Web Docs. [cited 2020 Aug 24]. 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Reference Source\n\nEmpowering App Development for Developers | Docker. [cited 2020 Aug 26]. Reference Source\n\nPérez N: BioSounds. 2020 [cited 2020 Aug 24]. Reference Source\n\nBioSounds: SoundEFForTS. [cited 2020 Aug 24]. Reference Source\n\nDarras K, Furnas B, Fitriawan I, et al.: Estimating bird detection distances in sound recordings for standardizing detection ranges and distance sampling. Methods Ecol Evol. 2018; 9(9): 1928–38. Publisher Full Text\n\nDarras K, Batáry P, Furnas BJ, et al.: Autonomous sound recording outperforms human observation for sampling birds: a systematic map and user guide. Ecol Appl. 2019; 29(6): e01954. PubMed Abstract | Publisher Full Text\n\ncontributors phpMyAdmin: phpMyAdmin. phpMyAdmin. [cited 2020 Aug 22]. Reference Source\n\nDarras K, Rahman D, Sugito W, et al.: Birds of primary and secondary forest and shrub habitats in the peat swamp of Berbak National Park, Sumatra [version 2; peer review: 2 approved]. F1000Res. 2018; 7: 229. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDenmead LH, Darras K, Clough Y, et al.: The role of ants, birds and bats for ecosystem functions and yield in oil palm plantations. Ecology. 2017; 98(7): 1945–56. PubMed Abstract | Publisher Full Text\n\nPaoletti A, Darras K, Jayanto H, et al.: Amphibian and reptile communities of upland and riparian sites across Indonesian oil palm, rubber and forest. Glob Ecol Conserv. 2018; 16: e00492. Publisher Full Text\n\nRhinehart T: Open source, scalable acoustic classification for ecology and conservation: opensoundscape. kitzeslab; 2019 [cited 2019 Aug 15]. Reference Source\n\nNoriega F: Tools for annotating and processing bioacoustic recordings: pylotwhale. 2019 [cited 2019 Aug 15]. Reference Source\n\nBuxton RT, McKenna MF, Clapp M, et al.: Efficacy of extracting indices from large-scale acoustic recordings to monitor biodiversity. Conserv Biol. 2018; 32(5): 1174–84. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPerez N, Darras K: BioSounds v1.0.0 (Version v1.0.0). Zenodo. 2020. http://www.doi.org/10.5281/zenodo.4047711"
}
|
[
{
"id": "74102",
"date": "10 Nov 2020",
"name": "Sarab S. Sethi",
"expertise": [
"Reviewer Expertise eco-acoustics",
"bioacoustics",
"ecological monitoring",
"software 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\nIn this study Darras et. al present Biosounds, an open source web-based platform for archiving, exploring, and tagging eco-acoustic data. The tool fulfills an important role, and provides ecologists with a user friendly, powerful tool for managing data acquired from projects deploying acoustics.\nWhilst the paper was generally well written and clear, my line by line recommendations/comments are as follows:\nIntroduction\n“19 reported software tools by Priyadarshani” consider rephrasing to “19 software tools reviewed by…” to ensure it is clear that these tools weren’t developed by Priyadarshani et. al.\n\nTable 1 presents a comprehensive comparison between Biosounds and other tools. However, it is difficult to parse efficiently in its current format, with a large number of factors to consider, and sorting all the options just alphabetically. Maybe sorting from most to least features, or grouping tools in some way would allow for faster comparisons to be made between the offerings. Additionally, wherever it is placed, putting Biosounds in bold would improve the table.\n\nTable 2, whilst again comprehensive, is arguably not too interesting. Picking out the key few differences and presenting them inline in the text may be a clearer way to present this information – readers are perhaps unlikely to read through the entire page long table. The full table could then be left in supplementary materials\nMethods\n“by computing a fast fourier transform” – what are the parameters for this? And why were they chosen? Are they customisable / do they adapt based on recording parameters?\n\n“Soundscape collections, due to their larger size, can be integrated up to a manageable size” – giving an indicative size in GB/TB is crucial for readers to assess whether this tool is suitable for their own projects.\n\n“upload recordings in most common audio formats” – please detail exactly which formats are supported.\n\n“MP3s of the audio file are generated after insertion into the database” – are the original uploaded audio files retained on the server (e.g., in the case of raw WAV files being uploaded)? Can the users download these back at a later date, or only MP3s? How are the MP3s generated (which codec) and at which compression level?\nUse-cases\n“distances are estimated in a standardised way” – how? Using spherical sound absorption assumptions, or by other means? Also, how is distance estimated without knowing the typical source SPL value of a species’ call?\n\n“export the tag data through a MySQL database” – are users (not administrators) also able to access this data? It would also be useful to add CSV export option for those not so comfortable with SQL DBs.\n\n“bat morphospecies …. named with single letters from A to J” – you should either detail how these morphospecies differ (what are the identifying call characteristics that places a bat in B for example), or if irrelevant leave out this level of detail and just mention that morphospecies are supported too.\nI also had a play around with the live demo running at https://soundefforts.uni-goettingen.de/biosounds/. My overall impression was very positive – the site was intuitive to interact with and things generally worked as advertised. I do have a few very minor recommendations below but appreciate that fulfilling these may be more difficult than the suggested manuscript changes:\nOpening the player view for a large file can take some time, and it just seems as if the connection has dropped (until finally the page is ready). This is not an issue when going forward and backward within the collection as there is a loading overlay, which makes it clear what is happening.\n\nWhen loading a large file into the player view the “play” icon is grayed out until some background loading is done. It isn’t clear that this is happening until this is done though – maybe a loading indicator in place of the gray play icon would be clearer.\n\nOnce I’d zoomed in on a part of the spectrogram I couldn’t return to the original, zoomed-out view without refreshing the page. This should be possible.\n\nWhen in the player mode there is no indication of sampling frequency or labels on the spectrogram’s Y axis. This info can be inferred from the frequency selection box values, but it should be more clearly apparent in my opinion as it is such an important piece of information. If an expert is searching for calls from a specific species, frequency labels on the Y axis can make this a lot quicker.\n\nWhen searching through a collection, if you click on a species from the dropdown prompt, the expected behaviour is that the search will be performed. However, instead a search isn’t actually triggered until you click the search button manually.\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": "9312",
"date": "07 Mar 2023",
"name": "Kevin Darras",
"role": "Author Response",
"response": "Thank you for the detailed appraisal of our work. In the meantime, we have deployed a new version (adding project management, acoustic indices, phonies, maps, timelines) and addressed your comments. Introduction: We removed the ambiguous sentence, which was mentioned in the discussion anyway. ecoSound-web is now in bold, and the Table 1 structure follows the classification of purposes announced in the introduction. Table 2 was deleted. Methods: We newly implemented FFT window size settings for the users (globally and per recording) and mention the available values in the text. We removed the uninformative “manageable size” and mention the user self-registration feature (which depends on long-term funding) in the conclusion’s goals. Regarding the SoX audio formats: the list is too long so we prefer to refer to the SoX homepage with a citation, but you can find them at https://sox.sourceforge.net/soxformat.html. We now mention that original audio files are retained on the server, but we don’t provide download features yet (see issue #99 on GitHub). Use cases: We already provide a citation (10.1111/2041-210X.13031) for the standardised estimation of the detection distances but added some more information to make clear that the reference recordings help human listeners to estimate distances. We now offer CSV export functions for the various data tables (tags, recordings, collections, acoustic indices) that are accessible to users with variable privileges instead of the impractical MySQL access option. Finally, the mention about using letters to distinguish morphospecies (we use “sonotypes” instead) was removed too. Regarding general usability comments: Spectrogram computation is still time-consuming as it is computationally demanding, but we implemented on-demand audio loading: the playback button can be clicked, it will become gray while the audio is loaded, and start playback and transform into a pause button. This avoids downloading large files for users who are only tagging visually (e.g., for bat recordings). We have restored the functionality for returning to the previous spectrogram view with an instant back browser button press. However, we decided to keep the time and frequency indications inside the selection boxes only instead of adding scales, as we find that information redundant and haven’t found a best practice implementation yet (but see issue #162). Finally, our new collection search function instantly searches across all the files’ meta-data and does not require a search button press."
}
]
},
{
"id": "74280",
"date": "20 Nov 2020",
"name": "Erin M. Bayne",
"expertise": [
"Reviewer Expertise I am working in very similar areas trying to achieve a similar objective. My group uses ARUs for a multitude of objectives and needed a tool that could do what is described here. We took a different path than Biosounds but what they have developed is an excellent resource I can see drawing from."
],
"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\nBiosounds is a very important step forward in the field of bioacoustics. Being able to manage large volumes of digital audio files and the various data that result is a large task that requires \"big data\" tools. Biosounds is a great step in this direction that continues on from past efforts. I greatly appreciate the efforts the authors have taken to continue developing tools that already existed. Building off of those tools and bringing them together into an easily setup system is a big advance.\nA gap in this particular draft of the paper are other similar efforts that do exist. For example, the group I work with has developed Wildtrax (www.wildtrax.ca) that has been operational for several years in Canada. This online system is used by partner agencies in provincial and federal governments, not for profits, industry, and academia. It has similar processes to Biosounds in the area of bioacoustics while also providing a platform for the storage of digital images taken by remote cameras. Including this effort as part of the comparison seems warranted. The key difference is Wildtrax is a centralized database system with the goal of sharing data amongst users Canada-wide rather than have each group setup their own server etc. It too is in development and has many things in common with the list of things Biosounds would like to see developed. The key difference seems to be that we have centralized the process and focused on users bringing their data to one place rather than managing things individually.\nWhile the rationale for WildTrax and Biosounds are different, it does raise what I think is a very important point that would help expand this paper. How do we use tools like WildTrax and Biosounds to create international collaborations and data sharing standards and where might this repository lie? This paper is an excellent description of a wonderful tool but how users that download and setup servers, etc., should consider sharing/using data together is underemphasized. By providing this type of tool Biosounds provides the infrastructure to help us start developing this vision but I feel this paper should also include at least a section for how we should discuss something greater through shared centralized repositories that build off initiatives like Biosounds and WildTrax. Whether a country by country nodal structure is an option that should be discussed rather than having individual labs, researchers, or local government departments create their own systems is the next step in determining how we can better utilize the amazing power that autonomous recording devices give us. A discussion of how such a process might be facilitated internationally (i.e. through ornithological societies, bat societies, etc.) would help develop the vision that I think Darras et al. and others envision.\nDarras et al must be complemented for developing such a useful tool that will undoubtedly improve the field of bioacoustics immeasurably. It is now up to the bioacoustics and wildlife biology fields to determine the best ways of making this data the most useful for the advancement of science and conservation.\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": "9313",
"date": "07 Mar 2023",
"name": "Kevin Darras",
"role": "Author Response",
"response": "Thank you for your very interesting, complementary appreciation of our work. In the meantime, we have deployed a new version, adding project management, acoustic indices, phonies, maps, and timelines to ecoSound-web. We have discussed the important points you raised in the conclusion with a new paragraph, and we adapted the goals to emphasize inter-operability. These points, together with the need for standards, are also themes in the focus of the first authors’ current research projects and interests, which will be expanded further in the next article iteration and website version (c.f. GitHub issues). Note that we already implemented DOI referencing and the choice of Creative Commons licenses for the recordings."
}
]
}
] | 1
|
https://f1000research.com/articles/9-1224
|
https://f1000research.com/articles/13-1336/v1
|
07 Nov 24
|
{
"type": "Study Protocol",
"title": "Child health, nutrition and gut microbiota development during the first two years of life; study protocol of a prospective cohort study from the Khyber Pakhtunkhwa, Pakistan",
"authors": [
"Muhamamd Shahzad",
"Muhammad Ismail",
"Benjamin Misselwitz",
"Ahsan Saidal",
"Simon C Andrews",
"Khalid Iqbal",
"Hatice Akarsu",
"Ziad Al Nabhani",
"Muhammad Ismail",
"Benjamin Misselwitz",
"Ahsan Saidal",
"Simon C Andrews",
"Khalid Iqbal",
"Hatice Akarsu"
],
"abstract": "Recent evidence suggests that the development of gut microbiota during infancy affects several metabolic, immune, and endocrine pathways in humans. An imbalance in gut microbiota diversity or function, also known as dysbiosis, not only affects early child growth and development, but is also linked with the development of chronic, non-communicable diseases in later life. The Child Health And Microbiome Development Study – Pakistan (CHAMP) study aimed to longitudinally assess gut microbiota development and associated factors (maternal, child, and demographic) during early childhood in populations residing in malnutrition-endemic communities in Pakistan. A prospective cohort of mother-infant pairs (n=70) will be recruited from District Swat, Pakistan, and followed for two years. Complete information about demographic characteristics, anti-natal and post-natal care, dietary intake, feeding practices, and child health will be collected at baseline and 3, 6, 12, 18, and 24 months. Anthropometric measurements (height, weight, mid-upper arm circumference, and head circumference), dry blood spots, and fecal samples were also collected. Ethical approval for the study was obtained from Khyber Medical University, Pakistan. The study is also registered on clincaltrial.gov (Ref no: NCT05793294). The study findings will help researchers understand gut microbiota development, associated factors, and their impact on longitudinal growth in infants during the first two years of life.",
"keywords": [
"Microbiome",
"Infants",
"Growth",
"Vulnerable",
"Malnutrition"
],
"content": "Introduction\n\nInfancy, the period from birth to around two years of age, is a crucial stage in human development, characterized primarily by rapid physical, mental, and emotional growth.1 During this period, many environmental factors such as gestational age, sex, ethnicity, dietary intake, nutritional status, and socioeconomic conditions significantly affect child growth, development, and overall health.2,3 However, to date, these factors, either alone or synergistically, have failed to explain the overall spectrum and variations in children. Recent studies have emphasized that apart from the intersection of environmental factors, the gut microbiome also plays an important role in mediating growth and development, especially during infancy.\n\nThe human fetus is believed to develop in a microbe-free environment.4 However, immediately after birth, the infant gut, especially the distal ileum and colon, is rapidly colonized by different microorganisms (bacteria, fungi, archaea, and viruses) via vertical transmission from maternal body sites such as the vagina, skin, oral cavity, and gut.5 In newborn infants, the gut microbiota exhibits low diversity, consisting mainly of facultative anaerobic bacteria, such as Proteobacteria (e.g., Escherichia and Enterobacter) and Firmicutes (Staphylococcus, Enterococcusand, and Streptococcus).6 Early colonization has a profound influence on the gut environment and subsequent colonization by obligate anaerobes, such as Bifidobacterium, Bacteroides and Clostridium. The relative abundance of Bifidobacteria gradually increases 3 – 4 days after birth and becomes a predominant bacterial genus when the baby is approximately 1 month old.7,8 In healthy growing children, the gut microbiota gradually increases in complexity with a highly diverse microbial composition during and after the first two–three years of life.9 During this period, the patterned ecological assembly of microbes occurs mainly under the influence of delivery mode, type of feeding, complimentary feeding practices, antibiotic use, and geography.9–12 Gut microbiota development during early life affects several metabolic, immune, and endocrine pathways and is thus intimately linked to child growth and development.13 Therefore, any disturbances in the host-microbe coevolution, microbial composition, or functional potential of the gut microbiome, commonly referred to as microbial dysbiosis, can impair immune function, growth, and development in children.\n\nIn recent years, several studies have reported associations between gut microbiome dysbiosis and impaired growth and development in children from different countries across the word. For example, a causal relationship between gut microbiome immaturity, undernutrition, and impaired growth has been reported in 6- and 18-months old children.14 Similarly, a Swedish cohort encompassing 471 children has also reported significantly lower microbial diversity and reduced abundance of Faecalibacterium and Ruminococcus in the gut microbiome of children with slower weight gain compared to normal children.15 Research studies from developing countries, where malnutrition is common, have also reported impaired or immature gut microbiome in malnourished (stunting, wasting, and underweight) children compared to that in healthy controls. In Bangladesh, children with severe acute malnutrition (SAM) exhibit a considerably less diverse gut microbiome, low relative abundance of Bacteroidetes and high relative abundance of Proteobacteria especially the pathogen/pathobiont genera such as Klebsiella, Escherichia, Shigella, and Streptococcus.16 In another study of a group of SAM infants aged 6–24 months, the absolute abundance of B. infantis was considerably lower than that of age-matched healthy infants.17 These findings were also confirmed by studies conducted in other developing countries in Asia and Africa.18–20 Altogether, these findings suggest that an immature/poorly developed gut microbiome in infants and young children is associated with malnutrition and its consequences, particularly impaired growth and development. As a result, a nutritional intervention strategy that does not consider the gut microbiome will fail to ameliorate the long-term consequences of malnutrition, including child health and cognitive development.21 Clinical studies in animals and humans have already demonstrated the positive impact of microbiome-based nutritional interventions on the gut microbiome and ponderal growth.22,23 These findings may have important implications for low- and middle-income countries such as Pakistan, where malnutrition in children is a crucial public health challenge.\n\nPakistan is the 5th most populous country in the world (approximately 250 million people)24 with enormous economic, geopolitical, social, and poverty-related challenges.25 According to the latest national nutrition survey, the prevalence of stunting (40.2%), wasting (17.7%), and micronutrient deficiencies in children under five years of age26 remained unacceptably high. Over the last five years, the country has been placed in the “Serious” category of the Global Hunger Index.27 The consequences of malnutrition are also economically catastrophic with $7.6 billion/annum (~3% of GDP) lost to malnutrition.28 Over the last two decades, there has been virtually no improvement in the overall nutritional status of the Pakistani population, despite efforts from the government and developmental organizations. Without coordinated efforts, it is very unlikely that Pakistan will achieve the UN Sustainable Development Goals to end hunger and all forms of malnutrition by 2030.29 Successful tackling this issue requires cost-effective, culturally relevant, and sustainable nutritional interventions. Keeping in mind the central role of the gut microbiome in mediating malnutrition in children, it is crucial to map the compositional and functional dynamics of the gut microbiome and associated maternal, child, and environment-related factors during early childhood in populations residing in malnourished communities in Pakistan. Therefore, the current study attempts to characterize how the gut microbiome develops in a cohort of children at high risk of malnutrition in the Khyber Pakhtunkhwa province of Pakistan.\n\n\nProtocol\n\nThe primary objective of the CHAMP study is to characterize gut microbiota development and longitudinal growth in infants during the first two years of life. This will be done by assessing the microbial diversity, relative abundance of the dominant microbiota, and interindividual variations in microbial diversity and infant growth patterns. The secondary objective of the study is to investigate the impact of (i) sociodemographic characteristics, (ii) mode of delivery, (iii) maternal factors such as diet and anti-natal and post-natal care, (iv) child dietary intake and feeding practices, and (v) nutritional status of the child on gut microbiota composition at different time points from birth until the child is two years old.\n\n\n\n• Nutritional status: The nutritional status of the child will be measured in terms of weight for age (WAZ), height for age (HAZ), and weight for height (WHZ) according to the WHO reference range.30\n\n• Underweight: Defined as weight for age of the child below two standard deviations (-2SD) from the median weight for age of the reference population.\n\n• Stunting: Child height for age below minus two standard deviations (-2SD) from the median height for the age of the reference population.\n\n• Wasting: Child weight for height below minus two standard deviations (-2SD) from the median weight for height of the reference population.\n\nThe CHAMP study was a population-based, prospective cohort study involving mother-infant pairs (dyads) from District Swat, Pakistan. Swat is located at 34°46′58″ N and 72°21′43″ N in Khyber Pakhtunkhwa province of Pakistan and is home to more than 2.3 million people.31 Because of its geographic location in the Hindukush–Himalayan region, most of the land is occupied by mountains and thick forests. The area is one of the most marginalized and neglected regions of the province, with livestock, agriculture, horticulture, and tourism as the primary sources of income and livelihood of the local population.32 Swat is among the most vulnerable districts in Pakistan and is prone to climate change. Since 2010, the district has been hit by at least three major floods that have significantly disrupted essential services, such as healthcare, sanitation, and access to safe drinking water.33 As a result, the majority of the population, especially children, are at a high risk of malnutrition and its deleterious consequences.\n\nAdministratively, the district is divided into seven administrative units known as Tehsil Municipal Administration units (TMAs). Tehsil Matta was chosen as the study area because it is the second most populated tehsil in Swat district, with the highest number of rural and remote communities. Following a preliminary survey, UC Beha was selected as the study site for several reasons. It is located at a high altitude with the longest adjoining borders with district Dir (Upper), and most of the population lives in agropastoral communities with very limited access to education and healthcare facilities. In winter, access to the area is limited by heavy snowfall and landslides.\n\nDistrict swats are divided into seven administrative units known as Tehsil Municipal Administration units (TMAs). Of these, tehsil Matta was chosen as the study area because it is the second most populated tehsil in Swat district, located at a high altitude with the longest adjoining borders with Dir district (Upper), which has the highest number of rural and remote communities. The Matta tehsil is further divided into union ouncils, which are the primary administrative institutions in Pakistan. In rural areas, union councils are referred to as village councils. Of the 13 village councils in the sampling area, three union councils were randomly selected as the primary sampling unit. Subsequently, the researchers visited the primary health centers and designated vaccination centers within the chosen village councils. Newborn children were identified using the Extended Program for Immunization (EPI) register. Potential participants were appraoched with the help of Lady Health Workers (LHWs), community-based health workers linked to local health facilities. All families in the area were registered with a designated LHW who regularly visited them. Important information, such as the child’s name, father’s name, date of birth, and address, was recorded, and a list of eligible study participants was prepared. Once recruited, each participant will be followed up for two years. The study follows ethical principles involving human subjects as outlined in the declaration of Helsinki. Ethical approval for this study was granted by the Ethics Board of Khyber Medical University, Pakistan ref no DIR/KMU-EB/BR/001-03 dated 11/01/2024.\n\nThe study population included 70 mother-infant pairs (dyads), according to the following criteria:\n\nInclusion criteria\n\n• Apparently healthy infants of both genders aged 0 – 28 days\n\n• Born by natural or caesarean delivery\n\n• Born to parents from district Swat\n\n• Parents/caregivers have no plans to move out of the stud site for at least two years after enrollment in the study.\n\nThe exclusion criteria are:\n\n• Child born to an underage (<18 years old) mother.\n\n• Infants born with severe acute or chronic medical conditions that require hospitalization, prolonged use of medication, or both, or diagnosed with enteropathies.\n\n• Weight of the child is <1500 gm.\n\nEthical approval for the study was granted by the Research Ethics Board of Khyber Medical University. This study was also registered at www.clinicaltrial.gov (NCT05793294).\n\nIn the local (Pashtun) culture, it is not possible to directly contact a potential female study participant without prior consent from the husband/male head of the household. Therefore, at each study site, an initial information session was held with the male parents/guardians with the help of elected local representatives and elders of the community. During the session, complete information about the study objectives, eligibility criteria, and data collection process was presented and explained by the team leader in the local (Pashto) language. A participant information sheet containing all the study details and procedures in an easy-to-understand, local (Pashto), and Urdu (national language of Pakistan) were also provided to the parents during the session. All queries were also answered. Following the session, eligible parents/guardians were invited by trained research assistants to enroll their babies in the study. Once they agreed, the parents were asked to sign a written informed consent form in their preferred language.\n\nCommunity members, funder (NIH Pakistan) or the participants’ parents were not directly involved in developing the study design, conduct, and outcome measures. The study protocol was reviewed and approved by the Office of Research, Innovation, and Commercialization (ORIC) Khyber Medical University and National Institute of Health (NIH), Pakistan. Healthcare professionals (LHWs) involved in the study had close liaison with the community and acted as a bridge between the researchers and participants. They also contributed to the design of the data collection questionnaires, informed consent, and helped ensure confidentiality. However, the individual data were not reported to the participants.\n\nFigure 1 provides an overview of the overall study flow.\n\nWe will collect different data from both mother and infant at baseline and at each time point during the follow-up period. The data collection in this project used an Android version of the KoBoCollect/Toolbox as a data collection instrument. To collect the demographic and socioeconomic information of the study participants, an interviewer administered a structured questionnaire will be used. The questionnaire included information such as name, age, sex, household information, and socioeconomic status. Details about ante-natal and post-natal care will also be recorded using a structured, validated questionnaire adapted from the National Nutrition Survey Pakistan questionnaire.34 These data were recorded only at baseline, that is, at the start of the study.\n\nThe Dietary Quality Questionnaire (DQQ) was used to assess the dietary intake of mothers. This method was chosen because, in Pakistan, there is no validated food frequency questionnaire to assess dietary intake. The DQQ is a standardized and easy-to-use tool to collect food group consumption data required for calculating diet quality indicators, such as Minimum Dietary Diversity for Women (MDD-W). The questionnaire has been validated and implemented across more than 100 countries including Pakistan.35 The DQQ is a list-based method consisting of yes/no responses to 29 food groups consumed by the respondent during the previous day and night (24 hours). The procedure typically requires approximately 5–7 minutes to complete. Information regarding feeding practices of the children will be collected using validated, semi-structured questionnaires based on Infant and Young Child Feeding Practices (IYCF) indicators developed by the Technical Expert Advisory Group on Nutrition Monitoring (TEAM) of the WHO.36 This set of simple, validated, and reliable indicators is widely used to assess IYCF practices across the globe, especially in low- and middle-income countries. The IYCF indicators were assessed by interviewing the mothers or the main caregivers. The mothers will also be interviewed to collect data about the child’s medical history, diarrhea and respiratory tract infection, hospitalization, and use of antibiotics using a structured questionnaire. DQQ, IYCF, and child health record data will be collected at baseline and at each time point during follow-up.\n\nAt baseline and at each time point, the following anthropometric assessment will be performed on each child/infant and their mothers using standard methods.37\n\nHeight/length: Recumbent length will be measured using an infantometer. Before measuring, the measuring board will be placed on a hard, flat surface such as a ground or sturdy table. The mother was asked to place the child gently on the board such that the infant’s head is aligned against the headboard while an assistant straightens the infant body and feet. When the child is position is correct, the researcher moves the foot board firmly against the child’s heels. The length of the child is recorded to the nearest 0.1 cm. The measurement will be repeated twice, and the average of the two measurements is recorded as the final length of the child. Mothers’ height will be recorded using a stadiometer following standard protocols. Briefly, they will be asked to remove shoes and gently stand on stadiometer. To ensure accurate measurement, the mothers will be instructed to stand up against the board, ensuring the Frankfurt plan position in which the back of the head, shoulder blades and buttocks and heels touch the back of the stadiometer. Once ready, the researcher will gently and firmly slide the measuring board’s moveable headpiece down until it touches the crown of the person’s head (compresses the hair). The procedure is repeated twice and the average of the two measurements is recorded as the height of the mother.\n\nWeight: To record the weight of the child, a specialized electronic scale (Secca, UK) will be used. Before weighing the child, the parent will be instructed/helped to remove shoes, socks and heavy clothing except dry clean diapers or underpants from the child. When ready, the child is placed on his/her back on the center of the scale pan with the help of a trained researcher. We wait until the infant is still in the pan and the digital display is no more changing. The weight of the child is recorded to the nearest 0.01 kg. The weight of the mother is measured in kilograms using a calibrated electronic weighing scale. The mothers will be asked to remove shoes, jewellery and extra clothing (dupatta/chaddar) and stand calmly on the scale. The weight will be recorded to the nearest 0.01 kg twice and the average of the two measurement is considered the final weight of the mother.\n\nMid upper arm circumference (MUAC): For infant MUAC measurements, a non-stretchable, numbered and colored MUAC tape will be used. To prepare for the measurement, the infant mother will be asked to sit on a comfortable chair, place the child in her lap and remove any clothing covering the left hand of the child. The mid-point between the tip of the elbow and the shoulder is located by straightening the arm along the axis of the body and forearm at 90-degree forwards. Once the mid-point is marked with a pen, the arm is straightened and the MUAC tape is placed around the arm at the midpoint and the reading is taken to the nearest mm.\n\nHead circumference: The head circumference of the child will be measured using a non-stretchable measuring tap around the most prominent part of head to the middle of the forehead while the hair and soft tissue is compressed. At least two measurements will be recorded and the average of the two will be taken.\n\nDry blood spot: Dry blood spots (DBS) are collected from both the mother and the infant at baseline and during the follow-up by skin puncture of the third or fourth finger of the non-writing hand.38 Before DBS collection, the participants’ hands were first warmed, followed by anterograde massaging of the finger in the direction of blood flow towards the puncture site. The DBS collection site, that is, the palmar side of the tip of the distal phalanx, was cleaned with 70% isopropyl alcohol and punctured using a single-use lacet. The first drop of blood was wiped off with a gauze pad, and subsequent drops were transferred to the marked circles on the surface of the filter paper without touching the surface. After drying, the DBS papers were transferred to a zip-lock bag and stored at -80 °C until further processing in the KMU main lab.\n\nStool: Stool samples are collected from the diapers of infants at each time point. For this purpose, the parents were provided diapers, a specimen collection jar, disposable gloves, a zip lock bag, and an instruction sheet one day before sample collection. The parents were instructed to regularly check their child’s diaper and remove it immediately after the child passed the stool. Stool samples were transferred immediately to the specimen container, placed in a zip-lock bag, and handed over to the research assistant within 4 h of sample collection. The research assistant transferred 400 mg of stool sample into 2 mL screw-top tubes prefilled with DNA shield reagent (Zymo Research USA) and sent it to the main KMU lab at room temperature, where it was stored at -80 °C.\n\nHematological aassessment\n\nDry blood samples will be used to assess the biomarkers of infections, micronutrient deficiencies, and inflammation. For this purpose, commercially available chemiluminscence-based Q-plex Aray kits (Quansys Biosciences) will be used following the manufacturer’s instructions. This assay reliably detects and quantifies histidine-rich protein II (biomarker of malarial infections), C-reactive protein, alpha-1-acid glycoprotein (biomarkers of inflammation), ferritin and soluble transferrin receptor (biomarker of iron deficiency), retinol binding protein (biomarker of vitamin A deficiency), and thyroglobulin (biomarker of iodine deficiency). 39\n\nDNA extraction and 16S rRNA sequencing\n\nBacterial genomic DNA will be extracted from fecal samples (200 mg) stored at -80 °C using a ZymoBIOMICS DNA Miniprep Kit (Zymo Research, Irvine, CA, USA), following the manufacturer’s instructions. Each sample will be quantified using Denovix and quality was checked by PCR of the 16S rRNA gene target and agarose gel electrophoresis. For the amplicon PCR step, 12.5 ng of purified bacterial genomic DNA will be used to amplify the V3-V4 target region according to the manufacturer’s protocol. The amplified samples were then subjected to agarose gel electrophoresis to separate the DNA samples from the primer dimers. Each DNA band was extracted and purified using the QIAquick gel extraction kit (Cat. no. 28705; QIAGEN, Germany). After purification, the concentration of each amplicon PCR will be quantified using Nanodrop. Next, library preparation was performed via indexing PCR and the reaction was subsequently cleaned up and quantified, following the Illumina kit’s guidelines. The concentrations of all samples were then standardized to a minimum of 2.5 nmol. One microliter of DNA from each sample was pooled and sent for high-throughput sequencing on the Illumina Miseq® platform (Illumina, San Diego, California, USA) following the manufacturer’s instructions.\n\nMonitoring and evaluation strategy\n\nThe monitoring and evaluation of the entire project will be conducted at all levels. Data entry will be randomly rechecked for accuracy by re-interviews or re-visits to households participating in the study. The principal investigator oversees the data collectors and enumerators. Bimonthly assessments will be performed by the project team consisting of the project manager, the PI, and the co-PI. In addition, the KMU ORIC team will monitor the overall progress of the project through its own monitoring and evaluation system. Any discrepancy or deviance from the main objectives or lapse in the timeframe and data collection procedures will be handled in close coordination of the project team with the field data collector and support from KMU.\n\nA common issue in longitudinal cohort studies is systemic attrition, which can have a significant impact on the generalizability of the outcome of interest. Study participants may lose interest in the study and therefore decline their participation, especially in long-term cohort studies. Below is a list of the potential reasons for attrition in the current project and mitigation strategies.\n\n1. The first and most important reason might be that some participants left the study district permanently and left the research team unable to track and collect data at different time points. To tackle this issue, we have set our inclusion criteria such that only those participants who are permanent residents of these districts and who confirm that they have no plans to move outside the district permanently will be recruited.\n\n2. Reducing barriers to participation by hiring local research assistants and their training, ensuring anonymity, translating the data collection tools to the local language (Pashto), and pilot testing.\n\n3. A follow-up and reminder strategy was set up by calling the participants before data collection.\n\n4. Tracing via alternative phone numbers and visiting the house physically when participants did not respond.\n\nAll in sillico data processing and analysis will be performed on the IBU Linux Cluster for Rocky Linux 8 from the servers of the University of Bern on a local machine running Ubuntu 20.04.06 LTS (32GB, Intel® Core™ i7-9750H CPU @ 2.60GHz × 12) and within R (4.4.1 2024-06-14) package environments in RStudio (2024.04.2). Sequence reads obtained for each sample were processed for quality using FastQC (v0.11.9) and MultiQC (version 1.11). Further quality checks, read trimming, chimera removal, denoising, and taxonomy assignment (using a trained Naive Bayes kmer classifier) will be performed directly from within the QIIME2 workflow (q2cli version 2024.5.0) using the included DADA2 software. Standard core metrics such as alpha diversity indices (Faith’s richness, Simpson’s evenness, and Shannon index) and beta diversity (Bray-Curtis, weighted UniFrac for the quantitative metrics; jaccard and unweighted UniFrac for the qualitative ones; Aitchison) will be computed with QIIME2, then explored in Qiime2View, and further processed and compared with Phyloseq and qiime2R packages in R. We will use the Emperor biplot plugin, Principal Coordinate Analysis (PCoA), and beta-group-significance plugin to test beta diversity significance and characterize the top bacterial genera that explain the microbiota distributions across the samples.\n\nWe will seek to identify any correlations between the collected metadata and microbiome composition, and identify any gut/oral microbiota trends associated with nutritional status and food diversity. We decorticate the variations in the observed microbiota composition across different groups, such as weight, height, age, and nutritional status. For alpha diversity comparisons, the groups’ significance was computed and tested using Kruskal-Wallis pairwise tests. We will also use the q2-longitudinal plugin to investigate longitudinal and paired sample comparisons, that is, to determine if or how samples change between the different time points and treatments/nutrients. All postprocessing and statistical analyses will be performed in R.\n\nWeight for height, weight for age, and height for age z-score will be calculated using the WHO Anthroplus software and compared with microbiome composition using R.\n\nThe results of the study will be disseminated to the public and academia, including our research team and collaborators, scientists, and the broader research community via participation in scientific conferences, meetings, and publications in peer-reviewed journals.\n\nThe study began in 2024 and will continue until May 2026. As of October 2024, 70/70 (100%) were recruited. Data and samples were collected for the baseline (n=70) and first follow-up periods (3 months; n = 66).\n\n\nDiscussion\n\nThe CHAMP study aimed to longitudinally characterize gut microbiome development in newborn infants during the first two years of life and included 70 mother-infant pairs (dyads) recruited from remote, rural communities of District Swat, Pakistan. This study involved comprehensive data collection regarding dietary intake, nutritional status, infant growth, and morbidities at different time points. Prospective collection of stool samples will allow gut microbiome assessment over time and identify demographic, maternal, and child-related factors affecting its diversity and abundance. The study findings will contribute towards a better understanding of gut microbiome colonization and development, associated factors, and its impact on growth in infants from malnourished areas of Pakistan.\n\nMicrobial colonization of the gut during infancy plays a crucial role in establishing the intestinal barrier and developing the immune system.40 Numerous studies have reported rapid changes in the composition and diversity of the microbiota during the first two years of life in healthy infants. However, the pattern and extent of microbial colonization are largely influenced by feeding practices and nutritional status of infants. A bidirectional relationship exists between the development of the gut microbiome and nutritional status. Malnutrition can affect gut microbiome development and maturation during early childhood, resulting in dysbiosis. As a result, an immature and altered gut microbiome leads to malnutrition owing to impaired energy production, vitamin biosynthesis, and immune dysfunction.41,42 These findings are critical, especially in developing countries such as Pakistan, where childhood malnutrition is a public health issue.34 The CHAMP study will help to dissect the relationships between dietary intake, nutritional status, and gut microbiome phenotypes during infancy and pave the way for developing microbiome-based interventions to tackle the problem of malnutrition in Pakistan.\n\nOur study is the first to characterize gut microbiome development in newborn infants from malnourished areas of Pakistan. The study will greatly help to understand infant growth trajectory in relation to gut microbiome development and provide a conceptual basis for sustainable nutrition recommendations and interventions in the future. The prospective longitudinal nature of the study will help in the collection of detailed data with minimal constraints (six visits in 2 years) and associated risks (no intervention and minimally invasive procedures to collect biological samples). This study will obtain precise data on dietary intake and nutritional status and their short-term and medium-term impacts on gut microbiome development, and vice versa. To gain deeper insights into how these factors, especially dietary intake patterns and socioeconomic status, impact gut microbiome development, we will compare our study results with similar studies conducted in Zimbabwe, a low-income country (The University of Zimbabwe College of Health Sciences (UZ-CHS) Birht Cohort)43 and Switzerland, a high-income country (The Bern Birth Cohort – BeBiCo study).44 Both of these studies involved mother-infant pairs and collected neonatal data on demographics, socioeconomic status, and diet at time points corresponding to our study. These studies also collected fecal samples, which will allow us to compare gut microbiome development in Pakistani infants with infants from Switzerland and Zimbabwe, countries with completely different landscapes in terms of environmental, cultural, and dietary intake patterns.\n\nOur study has some limitations. First, the launch and implementation of a cohort study in remote, difficult-to-access rural areas are challenging, anywhere in the world, including Pakistan. As a result, dropout and attrition in the sample size are expected. Second, the study involved multiple assessments, requiring the mother to travel long distances in mountainous areas to reach the sampling site. The process is time-consuming and potentially burdensome to the mother and infants. However, these issues will be partly addressed by providing compensation for travel and sending advance reminders about follow-up visits using phone calls. Third, due to the self-reported and retrospective nature of the data collection during each visit, response and social desirability bias cannot be fully avoided. Finally, we could only identify the association between growth and gut microbiome development, but no causal relationship because of the non-interventional study design.\n\nThe study follows ethical principles involving human subjects as outlined in the declaration of Helsinki. Ethical approval for this study was granted by the Ethics Board of Khyber Medical University, Pakistan ref no DIR/KMU-EB/BR/001-03 dated 11/01/2024.\n\nIn the local (Pashtun) culture, it is not possible to directly contact a potential female study participant without prior consent from the husband/male head of the household. Therefore, at each study site, an initial information session was held with the male parents/guardians with the help of elected local representatives and elders of the community. During the session, complete information about the study objectives, eligibility criteria, and data collection process was presented and explained by the team leader in the local (Pashto) language. A participant information sheet containing all the study details and procedures in an easy-to-understand, local (Pashto), and Urdu (national language of Pakistan) were also provided to the parents during the session. All queries were also answered. Following the session, eligible parents/guardians were invited by trained research assistants to enrol their babies in the study. Once they agreed, the parents were asked to sign a written informed consent form in their preferred language.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nMuhammad, Shahzad, 2024, “Child health, nutrition and gut microbiota development during the first two years of life; study protocol of a prospective cohort study from the Khyber Pakhtunkhwa, Pakistan”, https://doi.org/10.7910/DVN/ROU3VJ 45\n\nThis project contains the following extended data:\n\n• Data Collection Quarionnaire.doc\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\nBornstein MH: Human Infancy … and the Rest of the Lifespan. Annu. Rev. Psychol. 2013 Sep 13; 65: 121–158. Publisher Full Text\n\nAlur P, Holla I, Hussain N: Impact of sex, race, and social determinants of health on neonatal outcomes. Front. Pediatr. 2024 Apr 9 [cited 2024 Oct 20]; 12. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThahir AIA, Li M, Holmes A, et al.: Exploring Factors Associated with Stunting in 6-Month-Old Children: A Population-Based Cohort Study in Sulawesi, Indonesia. Nutrients. 2023 Aug 1; 15(15): 3420. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDominguez-Bello MG, Costello EK, Contreras M, et al.: Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA. 2010 Jun 29; 107(26): 11971–11975. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFerretti P, Pasolli E, Tett A, et al.: Mother-to-Infant Microbial Transmission from Different Body Sites Shapes the Developing Infant Gut Microbiome. Cell Host Microbe. 2018 Jul 11; 24(1): 133–145.e5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBäckhed F, Roswall J, Peng Y, et al.: Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe. 2015 May 13; 17(5): 690–703. PubMed Abstract | Publisher Full Text\n\nBittinger K, Zhao C, Li Y, et al.: Bacterial colonization reprograms the neonatal gut metabolome. Nat. Microbiol. 2020 Jun; 5(6): 838–847. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHenderickx JGE, Zwittink RD, van Lingen RA , et al.: The Preterm Gut Microbiota: An Inconspicuous Challenge in Nutritional Neonatal Care. Front. Cell. Infect. Microbiol. 2019; 9: 85. PubMed Abstract | Publisher Full Text | Free Full Text\n\nStewart CJ, Ajami NJ, O’Brien JL, et al.: Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018 Oct; 562(7728): 583–588. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBeller L, Deboutte W, Falony G, et al.: Successional Stages in Infant Gut Microbiota Maturation. MBio. 2021 Dec 21; 12(6): e0185721. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlm MR, Dahan D, Carter MM, et al.: Robust variation in infant gut microbiome assembly across a spectrum of lifestyles. Science. 2022 Jun 10; 376(6598): 1220–1223. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXiao L, Wang J, Zheng J, et al.: Deterministic transition of enterotypes shapes the infant gut microbiome at an early age. Genome Biol. 2021 Aug 24; 22(1): 243. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRobertson RC, Manges AR, Finlay BB, et al.: The Human Microbiome and Child Growth - First 1000 Days and Beyond. Trends Microbiol. 2019 Feb; 27(2): 131–147. PubMed Abstract | Publisher Full Text\n\nBlanton LV, Charbonneau MR, Salih T, et al.: Gut bacteria that prevent growth impairments transmitted by microbiota from malnourished children. Science. 2016 Feb 19; 351(6275): aad3311. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRoswall J, Olsson LM, Kovatcheva-Datchary P, et al.: Developmental trajectory of the healthy human gut microbiota during the first 5 years of life. Cell Host Microbe. 2021 May 12; 29(5): 765–776.e3. PubMed Abstract | Publisher Full Text\n\nMonira S, Nakamura S, Gotoh K, et al.: Gut microbiota of healthy and malnourished children in bangladesh. Front. Microbiol. 2011; 2: 228.\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\nCamara A, Konate S, Tidjani Alou M, et al.: Clinical evidence of the role of Methanobrevibacter smithii in severe acute malnutrition. Sci. Rep. 2021 Mar 8; 11(1): 5426. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhan Mirzaei M, Khan MAA, Ghosh P, et al.: Bacteriophages Isolated from Stunted Children Can Regulate Gut Bacterial Communities in an Age-Specific Manner. Cell Host Microbe. 2020 Feb 12; 27(2): 199–212.e5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNabwera HM, Espinoza JL, Worwui A, et al.: Interactions between fecal gut microbiome, enteric pathogens, and energy regulating hormones among acutely malnourished rural Gambian children. EBioMedicine. 2021 Nov; 73: 103644. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMostafa I, Nahar NN, Islam MM, et al.: Proof-of-concept study of the efficacy of a microbiota-directed complementary food formulation (MDCF) for treating moderate acute malnutrition. BMC Public Health. 2020 Feb 17; 20(1): 242. 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.\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\nWorldometer: Countires in the world (by population).2024 [cited 2024 Oct 21]. Reference Source\n\nAfzal M: Brookings. Pakistan: Five major issues to watch in 2023.2023 [cited 2024 Oct 21]. Reference Source\n\nUNICEF: National Nutrition Survey 2018, Key findings report.2019. Reference Source\n\nGHI: Global Hunger Index (GHI) - peer-reviewed annual publication designed to comprehensively measure and track hunger at the global, regional, and country levels. Global Hunger Index 2024 - Pakistan.2024 [cited 2024 Oct 21]. Reference Source\n\nWFP: Malnutrition Costs Pakistan US$7.6 Billion Annually, New Study Reveals - Pakistan|ReliefWeb.2017 [cited 2024 Oct 21]. Reference Source\n\nKinyoki DK, Osgood-Zimmerman AE, Pickering BV, et al.: Mapping child growth failure across low- and middle-income countries. Nature. 2020 Jan; 577(7789): 231–234. Publisher Full Text\n\nWHO: The WHO Child Growth Standards. 2018 [cited 2024 Oct 21]. Reference Source\n\nPakistan Bureau of Statistics: Final Results (Census-2017)|Pakistan Bureau of Statistics.2017 [cited 2023 Apr 18]. Reference Source\n\nKhan SR, Khan SR: Assessing poverty–deforestation links: Evidence from Swat, Pakistan. Ecol. Econ. 2009 Aug 15; 68(10): 2607–2618. Publisher Full Text\n\nBazai NA, Alam M, Cui P, et al.: Dynamics and Impacts of Monsoon-Induced Geological Hazards: A 2022 Flood Study along the Swat River in Pakistan. Natural Hazards and Earth System Sciences Discussions. 2024 Jul 16; pp. 1–27.\n\nUNICEF Pakistan: National Nutrition Survey 2018.2018 [cited 2024 Oct 22]. Reference Source\n\nGlobal Diet Quality Project: Dietary Quality Questionnaire - Pakistan.2024 [cited 2024 Oct 22]. Reference Source\n\nWHO: Indicators for assessing infant and young child feeding practices: definitions and measurement methods.2021 [cited 2024 Oct 22]. Reference Source\n\nUSAID: Food and Nutrition Technical Assistance III Project (FANTA): Module 6 - Protocols and Equipments.2018 [cited 2024 Oct 22]. Reference Source\n\nGrüner N, Stambouli O, Ross RS: Dried Blood Spots - Preparing and Processing for Use in Immunoassays and in Molecular Techniques. J. Vis. Exp. 2015 Mar 13; 97: 52619. Publisher Full Text\n\nBrindle E, Lillis L, Barney R, et al.: Measurement of micronutrient deficiency associated biomarkers in dried blood spots using a multiplexed immunoarray. PLoS One. 2019 Jan 8; 14(1): e0210212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHoughteling PD, Walker WA: Why is initial bacterial colonization of the intestine important to the infant’s and child’s health?. J. Pediatr. Gastroenterol. Nutr. 2015 Mar; 60(3): 294–307. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIddrisu I, Monteagudo-Mera A, Poveda C, et al.: Malnutrition and Gut Microbiota in Children. Nutrients. 2021; 13(8). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMillion M, Diallo A, Raoult D: Gut microbiota and malnutrition. Microb. Pathog. 2017 May; 106: 127–138. Publisher Full Text\n\nDuri K, Gumbo FZ, Munjoma PT, et al.: The University of Zimbabwe College of Health Sciences (UZ-CHS) BIRTH COHORT study: rationale, design and methods. BMC Infect. Dis. 2020 Oct 2; 20(1): 725. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCecchini L, Barmaz C, Cea MJC, et al.: The Bern Birth Cohort (BeBiCo) to study the development of the infant intestinal microbiota in a high-resource setting in Switzerland: rationale, design, and methods. BMC Pediatr. 2023 Nov 10; 23(1): 560. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMuhammad S: Child health, nutrition and gut microbiota development during the first two years of life; study protocol of a prospective cohort study from the Khyber Pakhtunkhwa, Pakistan. Harvard Dataverse. 2024. Publisher Full Text"
}
|
[
{
"id": "358559",
"date": "05 Feb 2025",
"name": "Ryan Marsh",
"expertise": [
"Reviewer Expertise Gut microbiome research (Cystic Fibrosis)",
"utilising multi-omics."
],
"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,\nMany thanks for the opportunity to review this work. Please find below my comments to each section of the report.\nIs the rationale for, and objectives of, the study clearly described? (YES)\nThe Study Protocol presented here by Shahzad and colleagues undoubtedly addresses the warranted need to further understand early life microbial dynamics across infants from malnourished areas of Pakistan. Elucidating the relationships between the microbiome and early lifestyle factors will no doubt increase favourable outcomes throughout development in children from such regions.\nI have no qualms with the study rationale, and the body of literature cited for this work is of high quality and relatable to the study background.\nIs the study design appropriate for the research question? (PARTLY)\nOverall, I am happy with the study design, which provides a logical narrative. I understand that sampling may have already begun, but I would double check tense usage throughout just to be consistent and to amend any potential language errors.\nI understand a variety of questionnaires will be/are being used by the researchers to collect the relevant demographic information. Some clarity would be appreciated on the following:\nStudy Procedures, Data collection: First paragraph reads at the end: “These data were recorded only at baseline, that is, at the start of the study”. Does this refer only to the original demographic/socio-economic data, and not the ante-natal and post-natal care information? If the latter is included, I would highly recommend the authors specify examples of what this may encompass, as I believe elements of these may overlap with other questionnaires poised by the authors, such as antibiotic usage.\nAs for other areas of the sampling:\nIn-person sampling: It would be good to set or specify if there is a time-standardisation here upon arrival, as the limitations describe the burdensome journey that will have to be made by participants. This would be applicable to dry blood spot testing if this is to commence following this journey, which may skew data on inflammatory outcomes etc.\nSample collection: Given the authors highlight the potential translocation of bacterial taxa from various anatomical sites between mother and newborn, which specifies the gut of the (line 10, Introduction), it would have been very interesting to investigate the microbiota of the mother as close to the infants’ baseline sample as possible, to decipher if common seeding patterns that associate with favourable growth outcomes etc. Not sure if this can be feasibly integrated given the original ethical approvals put in place, but food for thought no doubt.\nAre sufficient details of the methods provided to allow replication by others? (PARTLY)\nOverall, I am happy with the methods provided.\nFor the proposed approach for investigation into microbial communities utilising 16S rRNA amplicon sequencing on the Illumina Miseq® platform, I would ask for the following information, as to more clearly allow methods to be replicated by others:\nDNA extraction and 16S rRNA sequencing: “Next, library preparation was performed via indexing PCR and the reaction was subsequently cleaned up and quantified, following the Illumina kit’s guidelines”. Can you please elaborate on which kit in particular is used for the second-step PCR and subsequent library clean-up, or was this done manually whilst referring to Illumina’s “16S Metagenomic Sequencing Library Preparation” document? If possible, I would also highly recommend the researchers quantify DNA using fluorometric approaches, such as the Qubit fluorometer if manually adjusting and normalising as hinted in the protocol, to ensure adequate sampling read depth across all participants.\nDNA extraction and 16S rRNA sequencing: Given that V3-V4 region is the target of interest, I am assuming that this will be performed using 2 × 300 bp, V3 chemistry? I would always recommend highlighting this if possible. From personal experience I have found that the reverse read (R2) can significantly drop-off on these kits. As the background literature cites differences at the genus level across the microbiome across infants from both developed, and developing studies, I might suggest V2 Chemistry targeting the V4 region (2 × 250 bp) to increase robustness of read depth and quality across samples, if genus-level comparisons are sufficient for the authors.\nDNA extraction and 16S rRNA sequencing: Mention of sequencing controls (and any positive mock community controls) would be useful.\nAs for the wider interpretations and considerations of the results/data:\nData analysis: The authors describe the relationships they are looking to explore between microbiota diversity and community composition with participant demographics they are looking to collect. Within the “data collection” section the protocol, it states: “The mothers will also be interviewed to collect data about the child’s medical history, diarrhea and respiratory tract infection, hospitalization, and use of antibiotics using a structured questionnaire”. I would anticipate the researchers to also investigate relationships between antibiotic usage and microbiota structure, but there is no specific mention of this (unlike nutritional status, food diversity, height, weight, age, etc..). Perturbation of intestinal microbial communities following antibiotic administration is well documented, which is of heightened importance during the developmentally critical age window (0-2 years) of the infants in this study. Additionally, I understand from the literature, that over-the-counter dispensation of antibiotics can be common in Pakistan which may increase the likelihood of a significant perturbation events to the intestinal microbiota.\n\nGeneral formatting (PARTLY)\nType errors:\n“ouncils” should read “councils” – Sampling technique paragraph, line 4.\n“measuring tap” should read “measuring tape” – Anthropometric assessment paragraph, line 1.\n“Hematological aassessment” – error in title of this section in the Laboratory analysis.\n\nOverall, I would advocate for the acceptance of the study protocol once these minor changes are implemented. I look forward to reading the final indexed study. Great work so far, and good luck moving forward!\nBest, Dr. Ryan Marsh\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? Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1336
|
https://f1000research.com/articles/13-1333/v1
|
07 Nov 24
|
{
"type": "Research Article",
"title": "Incentives in prescribing, dispensing and pharmaceutical spending: A scientometric mapping.",
"authors": [
"Tocaruncho-Ariza L. H",
"Riascos-Ochoa J",
"Jimenez-Barbosa W. G",
"Riascos-Ochoa J",
"Jimenez-Barbosa W. G"
],
"abstract": "Introduction Health systems worldwide are struggling to ensure the affordability of medicines. Prescription, dispensing, and pharmaceutical expenditures are key variables that highlight the need to understand how global scientific evidence is generated against factors (implicit and non-explicit) that influence these variables.\n\nObjectives To provide a panorama of scientific production on drug prescription and dispensing, and its relationship with pharmaceutical expenditure in health systems worldwide.\n\nMethods A five-stage scientometric mapping was performed based on a systematic search of 8 databases. The five stages are: i) retrieval, ii) migration, iii) analysis, iv) visualization and v) interpretation.\n\nResults A corpus of evidence from 103 systematic literature reviews was obtained, screened and sifted, visualizing the countries, authors, databases, journals, institutions and time periods that contributed most to evidence generation. Central research themes are identified and phenomena related to article publication are discussed.\n\nConclusions The analysis reveals a clear leadership of the United Kingdom and the United States in scientific production on prescribing, dispensing and pharmaceutical expenditure in health systems worldwide. This scientific production is mainly focused on financing policies, pharmaceutical incentives and interventions, and rational use of medicines. There is also evidence of the scarcity of scientific production in Latin American publications and authors, which could generate interest for future research.",
"keywords": [
"Health systems",
"Drug financing",
"Price regulation",
"insurance",
"drug cost"
],
"content": "key points\n\nUsing the technique of scientometric mapping, our study characterizes the current state of global scientific production related to prescribing, dispensing, and pharmaceutical spending incentives in health systems worldwide in a rigorous and visually practical manner, providing a global and rapid overview of the dynamics of scientific literature production.\n\nIt also identifies, among other things, the main lines of publication, thematic leaders and representative authors, making it useful for other researchers or public policy makers.\n\n\n1. Introduction\n\nAffordability of medicines has been the focus of developing countries and global organizations, but it has now become a global issue.1 In recent decades, a number of events have concerned stakeholders in different healthcare systems around the world. For example, publicly funded pharmaceutical expenditures, drug shortages, technological pressures due to new drugs, effects of the COVID-19 pandemic (shortages of raw materials or derived pathologies), and economic availability. These phenomena have created uncertainty about the financial sustainability of health systems.\n\nGovernments are developing strategies to reduce the impact of these phenomena on the efficient provision of health services. However, those strategies that involve expenditure rationalization are the most worrisome because they seem to work only for a period of time and then lose their effectiveness. This behaviour is not new, and the World Health Organization (WHO) has called for a sincere and transparent dialogue between the actors in the pharmaceutical chain in order to achieve fairer prices.1\n\nInstead of “looking for” conventional market analysis factors such as frequency and price, or those related to a holistic and etiological approach to prescribing, we delve into factors related to philosophical and anthropological concepts such as ethics, customs, power relations, professional autonomy, moral risk,2 unfair competition, conflicts of interest, promotional incentives, handouts, loyalty strategies, asymmetric information, or any other factor that influences the actors in the drug chain and affects the sustainability of a health system.\n\nThese last factors become more relevant considering that a health system that obeys its coverage and efficiency in spending should mitigate the failures in achieving its objectives and strive for its sustainability and market equity. Also, the health system should evaluate the regulation of the health authority from a scenario where all stakeholders are satisfied.3\n\nTo characterize define the behavior of these additional factors, it is necessary to first observe how the evidence around the world on these topics is generated. Scientometric becomes a useful tool to perform this characterization. Scientometric is a technique that visualizes the quantitative aspects of the scientific literature and it is used as a tool for the development of scientific policies of countries and organizations.4\n\nScientometric mapping is a research method based on statistical and visualization methods to represent critical points and trends in a specific field. Therefore, it is proposed to take advantage of scientometric mappings that focus on the metrological characteristics of evidence and determine aspects such as publications, journals, countries, institutions, authors, keywords, and central research topics by defining representations of possible connections in a dynamically and continuously evolving scientific evidence system.5–7\n\nIn light of the above, the following research question arises.\n\nWhat are the characteristics of the production of scientific literature on prescribing and dispensing incentives and their relationship to pharmaceutical expenditures experienced by health systems worldwide?\n\nThe results of this scientometric mapping that visualizes scientific production will be complemented in a second research with a synthesis of evidence focused on the map review to analyze the trend of scientific production identified,8 and will be part of a doctoral research focused on identifying and analyzing the factors that influence the cost of prescribing, dispensing and cognitive costs of medicines in the Colombian health system from performance information from 2020 to 2022.\n\nFor all the above reasons, the main objective of this research is to explore the panorama of the world scientific production of Open Access articles related to the prescription and dispensing of medicines and their relationship with the pharmaceutical expenditure faced by health systems. The decision to study Open Access articles is justified by some principles of the Leiden Manifesto,9 which recommends that the processes of collecting and analyzing information should be open, transparent and simple, and that the data and analysis should be open to verification by the evaluators and reviewers; in this way, any reader can access the details of all the articles included in this academic exercise and expand the information that they consider relevant.\n\n\n2. Methods\n\nThis research has a descriptive scope developed by scientometric mapping, which includes five main stages4,10: recovery or selection of sources, migration or extraction of data, analysis, visualization and interpretation.\n\nA structured and rigorous research protocol was proposed, decomposing the research question into each of its components using the PICO structure (population, intervention, comparison and outcomes)11:\n\nPopulation: The study should include at least one of the following knowledge users:\n\n2.2.a Government decision makers\n\n2.2.b Policy advisors responsible for data analysis and reporting and recommendations for decision making\n\n2.2.c Administrators or stakeholders in public or private health systems, both at the level of policy implementers and providers\n\n2.2.d Scientific groups or societies\n\n2.2.e Users or patients\n\nIntervention: Studies will be considered that describe any strategy related to the analysis of prescription, dispensing, incentives and pharmaceutical expenditure of medicines in a health care setting.\n\nComparison: Articles with or without a comparison group were eligible for inclusion.\n\nOutcome: The selected outcomes of interest were those related to the identification of strategies, facilitators, barriers, and any other factors that allow establishing the relationship between prescribing, dispensing, incentives, and pharmaceutical expenditures.\n\n2.3.1 Inclusion criteria\n\n2.3.1.a Criteria for inclusion of studies in terms of format, language, and date of publication.\n\n- Article available as final publication, open access.\n\n- No language restriction.\n\n- No publication date restriction.\n\n2.3.1.b Criteria for study inclusion regarding design, methodological and reporting quality.\n\n- Type of study: Systematic Literature Reviews (SLR), which provide reliable information for health decision-making due to their rigorous and reproducible methodology, with specific objectives and eligibility criteria for the evidence, a systematic search and subsequent assessment of the validity of the results, and a structured synthesis. Compared with primary studies, SLR reduces the risk of bias in the selection and analysis of evidence, has less random error and greater statistical power when combining the results of different primary studies under comparison.12\n\n2.3.2 Exclusion criteria\n\nLetters to the editor, editorials, posters and comments were not included.\n\n\n3. Recovery\n\nThis phase included the following activities:\n\nDatabases were selected based on their bibliographic content and relevance to the research topic: Cochrane Database of Systematic Reviews (Wiley platform) with systematic reviews of controlled clinical trials and other studies,13 MEDLINE (Ovid platform or PubMed) for its amount of biomedical bibliography and to be of greater use worldwide,14 TRIP DATABASE (Turning Research Into Practice) (https://www.tripdatabase.com/, s.f.) specialized in clinical research, Science direct (Elsevier platform)15 with a multidisciplinary and peer-reviewed approach, EPISTEMONIKOS cataloged as a health evidence search engine with a large number of SLRs,16 the University of York: Database of Center Reviews Dissemination, which groups 3 databases that include SLR with previous quality review,17 some Latin American databases such as LILACS (Virtual Health Library - VHL) or international open access collaborations such as SCIELO (Scientific Electronic Library Online), and finally Google Scholar for complementary and optional evidence if needed.\n\nThe literature search was conducted on July 19, 2023 according to the search strategies described below.\n\nNatural language key words were identified from the research question. Search strategies were designed using DeCS controlled vocabulary (MeSH) and uncontrolled vocabulary (free language). The strategies were supplemented with the field identifiers title and abstract (.tw.), Boolean operators (OR and AND) and/or methodological filters according to the requirements of each database, without restriction of publication date or language, and full text available in open access.\n\nThe search strategies and results were stored in electronic format (Appendix 1. Search strategies) using a matrix previously designed in the Microsoft Excel® program. The first stage of article selection was performed by screening by reading the title and abstract and eliminating duplicates (Appendix 2. References deleted for duplicity).\n\nFull text screening was performed using the eligibility criteria. The results of the reference screening and study selection are presented in a process flow diagram (Appendix 3). In addition, the list of excluded studies and the reason for exclusion (Appendix 4) and the studies included in the research corpus (Appendix 5) are attached.\n\n\n4. Migration. Data extraction and synthesis of evidence\n\nIn a standard format designed a priori in the Microsoft Excel® program, the main data of each selected article and the findings of interest in relation to the outcomes proposed for this research were included, extracted by an expert reviewer in the field (Appendix 6. Data extraction and evidence synthesis variables).\n\n\n5. Results\n\n426 references were screened and 75 of them were excluded for duplicity. The remaining were read in title and full text as evidence screening, applying the eligibility criteria and excluding 249 studies for not meeting them. Finally, 103 articles to be included in the research are obtained.\n\nSince scientometric mapping is the quantitative processing of evidence,18 with the corpus of 103 selected references (hereinafter, research corpus), and from the 40 variables of the previously defined matrix (Appendix 6. Data extraction variables and evidence synthesis) were processed using electronic Microsoft Excel sheets, different relational tables of the variables (e.g., journal and country of origin of the publication, date of publication, affiliation of the lead author, funder), population characteristics and contextual factors (e.g., country of application, type of drug analyzed), and general findings of the SLR as a central theme, crossing this information with other sources to continue with the evidence visualization phase.\n\n\n6. Visualization\n\nThe results were presented considering the topics that could answer the research question and the general objective. For visualisation, all graphs presented in this section were created using Microsoft Excel 2019 MSO (16.0.10398.20008) 64-bit and the following free online software:\n\na. Tableau Public. Available at: https://www.tableau.com/products/public\n\nb. Power BI (Business Intelligence). Available at: https://www.microsoft.com/es-es/power-platform/products/power-bi\n\nc. Gephi. Available at https://gephi.org/\n\nd. Rawgraphs 2.0. Available at: https://www.rawgraphs.io/\n\ne. Word cloud from: https://www.nubedepalabras.es/\n\nf. Word cloud from: https://voyant-tools.org/\n\nThe themes analyzed were\n\na. Databases and publications\n\nb. Authors\n\nc. Citations\n\nd. Journals and Publications\n\ne. Institutions and Countries\n\nf. Funders and Sponsors\n\ng. Co-occurrence of terms\n\nh. Research trends\n\nScientific production related to prescription, dispensing and pharmaceutical expenditure is found from 1998 with the publication of an article (Figure 1), then a period in which publications were not identified until 2006, where again evidence was found related, although in the same number of annual generation, with an annual growth trend since 2010, reaching its highest value in 2022. The 2023 values are presented only up to the date of the evidence search carried out in July 2023, so this year’s data do not correspond to the entire annuity, but it was decided to include them because, contrary to the observed increasing trend, in seven months of 2023 only four articles were found. As of 2018, more than half of the total scientific output is concentrated in the research topic (52%).\n\nCompared to the number of primary studies included in the research corpus, according to the data from Table 1, it was observed that the SLRs generally develop a broad search for evidence with an initial total harvest of more than 720,000 studies or primary sources, but when applying the screening and selection process, less than 1% of the total evidence recovered in each SLR is selected. These proportions are similar across all SLRs.\n\nThe annual scientific output per database consulted is summarized in Figure 2, where PUBMED presents the highest proportion of evidence with 61 articles (59.22%) of the research corpus covering the longest period of published articles (2006-2023). It is followed by Cochrane with 16 publications (15.53%) from 2009 to 2022 and Epistemonikos with 12 articles (11.65%) from 2007 to 2023.\n\nAll authors (main or co-authors) reported in the research corpus were listed, resulting in a total of 517 authors. The productivity of authors was analyzed using Lotka’s law, first proposed in 1926,19 which refers to a quantitative relationship between authors and contributions produced in a field over a given period of time. The interpretation of this productivity index given by Del Valle Salinas20 is as follows:\n\nProductivity level (PN): Low 0, Result: 0\n\nProductivity level (PN): Medium >0<1, Result: >0<1\n\nProductivity level (PN): High >1, Result: >1\n\nThe application of the calculation of this index was obtained as Salinas,20 and is shown in Table 2:\n\nIt was obtained for the 517 authors appearing in the research corpus:\n\nLow productivity 486 (94.00%) Authors with PN: 0\n\nMedium productivity 31 (6.00%) authors with 0<PN<1\n\nHigh productivity 0 (0.00%) Authors with PN>1\n\nAs for the collaboration between authors, only 2.91% of the articles report a single author (3 articles), while the concentration of authors between 3 and 6 authors is concentrated in 67.00% of the 103 articles. One of the 103 articles with 32 authors is a SLR conducted in Canada in 2022 (lead author: Squires JE) on the inappropriate use of clinical practices, overuse and underuse of medications, and includes a section with detailed contributions by name of 10 of the 32 authors (Figure 3).\n\nOnly one of the 517 authors (Oxman A.D.) appears in 5 articles of the research corpus, in all of them in the last place of the signature of the authors, which denotes his role as director of each of the SLR according to the interpretation FLAE: “first-last-author-emphasis”,21 all of them “Cochrane reviews” published in the Cochrane Database of Systematic Review. 8 authors sign in 3 articles, of which 1 of them (Franklin BD) presents the same situation as Oxman AD when he is the last author in the three articles, that is, as director, while in the remaining 7 cases the order in the signatures of authorship is presented as main author or co-author. Special cases are Grimshaw JM, Peñaloza B, Pantoja T and Herrera CA, as they are all present in the same 3 articles (Figure 4).\n\n22 authors sign co-authorships in 2 different articles of the research corpus, and the remaining 486 authors appear in only one article, that is, only 5.99% of the total authors are in the signature of authors in 2 or more articles.\n\nBy visualizing the total number of authors/co-authors per year and calculating the average number of authors/co-authors, we obtain the behavior of Figure 5, where we find that the number of authors/co-authors is directly proportional to the number of articles published in each year, but the average number of authors/co-authors is more stable, ranging between 4 and 6 authors per article (Figure 5).\n\nIn identifying which publications have greater visibility in the global evidence, a limitation was found since the databases used do not allow in all cases to know the number of citations, therefore they were quantified from the search in the same data source in which all the selected articles were found, using the citation that appears in Google Scholar, and recognizing that some authors have criticized the lack of rigor in the number of citations presented because it is not always accurate, either because there is no significant degree of duplication, because of the opacity in the selection of sources or because it could be susceptible to manipulation.22\n\nWhen looking at articles by number of citations and country of publication, the largest number of citations was concentrated in the last quartile of citations greater than 104, as seen in Figure 6, which coincides with articles representing 80% of the total citations, standing out in the top of Figure 7, Horne R.’s article with 1,212 citations, followed by Smith S.M., with 998 citations (with 2 publications, in 2016 and an update in 2021, which was not defined as a duplicate in the screening but is considered as a single publication for this analysis), and Shojania KG, with 5. 99; then Flodgren G, Teixeira Rodrigues, Simou and Radley, all with citations greater than 400, thus limiting the countries of the journals of publication of 13 in the research corpus to only 4 of the top 10, where it is the United Kingdom that together represents more than 2600 citations in five publications, followed by the United States with slightly more than 1800 citations in three articles. Table 3 shows the details of the publications with the most citations and variables and the countries where the primary studies were developed.\n\nIn order to find out how the research corpus behaves according to the journals in which it is published, Bradford’s law was used first, as follows:\n\n6.4.1 Bradford’s Law\n\nFirst proposed in 1934 and published in 1948, this law states that the production of articles in journals presents an uneven distribution, where a high number of articles are concentrated in a small number of journals and, conversely, a small number of articles are distributed in a large number of journals.23,24 Its graphical representation is made by 3 areas, each representing 33% of the publications, and estimates the exponential decrease in performance when expanding the bibliographic search in publishing journals.\n\nFor the research corpus, the core and each domain were defined with 34,33 articles, resulting in a descending order of publications in each journal, as shown in Table 4:\n\nAnd with these data visualized as shown in Figure 8, only 3 journals concentrate 33.98% of the SLR, then in increasing order, 22 journals and then 34 journals concentrate the next 33% of the SLR. The core is: Cochrane Database of Systematic Reviews (CDSR), PLoS One and BMJ Open as publishing journals.\n\nThe top journals (with 2 or more articles) were visualized in Figure 10, defining which belong to the core (Cochrane Database of Systematic Reviews, Plos One and BMJ Open) and which belong to zone 2 according to Bradford’s law. Figure 11 ranks the top among the total number of journals in which the research corpus was published, with a high publication difference compared to other journals:.\n\nJournals with the highest number of retrieved publications by research topic.\n\nSecond, the results obtained by region and country with more publications according to the journal are shown in Figure 11, and being CDSR and BMJ Open journals from the United Kingdom, the highest proportion of publications, more than 50% of the total, was observed in the region Western Europe and the country United Kingdom.\n\nThe regions and countries of each journal correspond to the ranking in Scimago Journal & Country Rank 2022.25\n\n6.4.2 Impact factor\n\nThe impact factor of each journal was visualized, according to the assigned quartile in Scimago Journal & Country Rank 2022, as an evaluation that the scientific community has about the journals in which the research corpus was published, which gives indications of the quality and relevance that has for an author to publish in them, based on their relative position in their field of study and, for this purpose, the assigned impact factor in the classification that Scimago Journal & Country Rank 2022 was used.\n\nIn this way, as shown in Figure 12, of the 59 journals in which the research corpus was published, approximately 70% of them were classified in the first quartile, that is, they have the highest impact index, followed by 10% in the second quartile.\n\nOnly in 3 cases of the reviews included in the corpus, the assigned quartile was not found, because it was not a publication in an indexed journal, but in a database: Newman M, published in 2012, and Hatef E, published in 2022, or because it had not been assigned at the time of analysis, as was the case with the publication of Okamoto E in 2007.\n\n6.4.3 Country of origin of the publication journal\n\nThe geographical origin of each journal was used, finding that the results maintain the same trend of previous results, leading the United Kingdom with more than 50% of the total publications, followed by the United States of America with 23%. The trend is higher in Europe than in the Americas, where the United States dominates. Only one article published in a South American journal was recovered (Figure 13).\n\nThe correspondence between the country of affiliation of the main author and the country of the journal where the article is published has been visualized by means of the Sankey diagram in Figure 14. It can be observed that nearly 57% of the total publications are published by authors from the United Kingdom, and that authors with a UK affiliation publish 80% of their articles in UK journals, 15% in the United States and only 5% in other countries.\n\nCountry of affiliation of lead author and country of journal of publication.\n\nSimilarly, authors affiliated to the United States of America publish 56% of their articles in United States journals, 31% in United Kingdom journals, and the remaining 13% in journals of other countries. Although Ireland ranks third in terms of number of journals, authors affiliated to Ireland did not publish in journals of this geographical location, but in the United Kingdom and the United States of America. Authors affiliated to Canada do not publish mostly in Canadian journals either, but 40% publish in UK journals, followed by 30% in the United States, 20% in the Netherlands, and only 10% in Canadian journals.\n\nThe affiliated entities of the main author that dominate the publication of articles are the universities in a proportion close to 80%, followed by entities of governmental level with 8%, being located hospitals, private companies of investigation and other organizations in the remaining proportions indicated in Table 5.\n\nThe countries that contribute the most to the generation of evidence according to the affiliation of the lead author are the United Kingdom with 20% of the research corpus, followed by the United States with 16%, Canada with 10% and Australia with 5%, which means that more than 50% of the publications are concentrated in only 4 out of 33 countries. The overall distribution is shown in Figure 15.\n\nPublications by country of affiliation of the main author for the research topic. 1998-2023.\n\nWe also visualized the countries where the primary studies that included each SLR of the research corpus were developed, finding a total of 826 origins of the studies developed in 132 countries. The origins were defined considering that if an SLR reported 6 primary studies and the 6 studies were developed in the UK, the number of origins was 1, but if the UK was mentioned in two different SLRs, it was counted as 2 origins. In this way, we found that the development environments of primary studies cover wider geographical regions, even if the SLR is published in a particular country. The 10 countries with the highest number of reported studies of these 826 origins are shown in Figure 16 and represent 39% of the total 826 origins.\n\nNumber of primary studies per country according to each SLR. 1998-2023.\n\nIt was considered important to know the relationship between the country of affiliation of the lead author and the country(ies) where the primary studies were developed, thus obtaining the visualization of Figure 17. For example, it can be observed that the SLRs in which the main author reported affiliation to the United States of America (A-USA) include a high proportion of primary studies developed in the USA (D-USA), but also a high proportion of studies developed in other latitudes. The opposite is true if we look at authors with affiliation to Qatar (A-Qatar) in the upper right corner of the graph, who include studies conducted in the same region of West Asia in the SLRs in which they participate as lead author: Bahrain (or Bahrain), United Arab Emirates, Jordan, Kuwait, Lebanon, Oman, Palestine, Qatar, and Saudi Arabia.\n\nSLR lead author's country of affiliation and countries of primary studies.\n\nThe arc diagram in Figure 18 shows the above correspondence in more detail. On the left are the top 5 countries of authors in the SLR that include a greater number of countries of primary studies (starting with A-). These are, in order, the United Kingdom, the United States of America, Canada, Malaysia, and Australia. Below are the countries with the highest proportion of primary studies (starting with D-). Although countries such as the United States of America, the United Kingdom, Canada, Australia and the Netherlands had more primary studies, the diversity of other countries of origin is also observed.\n\nAffiliation of the main author (SLR) and primary studies.\n\nTo further deepen the analysis, the relationships between the country in which each of the primary studies included in each SLR was conducted, the country of affiliation of the lead author, and the country of the journal in which the SLR was published (13 countries in Figure 7) were visualized using a Sankey diagram, yielding the relationships in Figure 19.\n\nTo visualize in more detail the behavior shown in the figure above, the same variables were visualized in Figure 20 for the countries where 80% of the primary studies are concentrated, the countries of affiliation of the main authors and the countries of the journals of publication of each SLR. Some interesting behaviors can be observed in this figure, since authors with affiliation in Portugal did not publish their SLR in journals of the United Kingdom and the United States of America, but in Portugal and the Netherlands, and perhaps in Portugal because the SLR included a primary study conducted in Portugal, although no relationship for publication in the Netherlands was identified. Similarly, authors from Malaysia published only in Turkey and the Netherlands, and the SLR published in the Netherlands included a primary study conducted at the same latitude with no link to Turkey.\n\nThe information reported in the sponsorship or funding section of each article in the research corpus was extracted, and it was found that 30% of the total 103 SLRs do not include this information. 25% report funding by a government agency at the national level only, and 8% do so by funding a university institution. The remaining 35% are distributed among different organizations or alliances between them (Table 6).\n\n* ETES Agency: Health Technology Assessment Agency.\n\nUsing a chord diagram to visualize the country of the organization funding each SLR and the country of affiliation of the lead author, it was found that a high proportion of institutions located in countries such as the United Kingdom and the United States of America fund authors with affiliations in the same country. Only a few countries, such as Switzerland, Norway, and China, among others, report funding for authors with affiliations in other countries (Figure 21).\n\nTwo methods were used to identify the cooccurrence of terms. In the first one, the keywords contained in each article were visualized by means of a word cloud, considering that if the keywords were bigrams or n-grams, they were joined by means of a hyphen under “_” to make them visible in the word cloud in the same way. The result is shown in Figure 22, where the frequency of terms is proportional to the size of the word, with terms predominating:\n\nIn the second method, the research corpus was loaded into the Voyant tools to fully capture the terms of each article.\n\nA term cleanup was performed because loading each article includes terms that could skew the results of the word cloud. The cleanup was performed as follows:\n\na. Plural nouns were changed to singular if the word was previously singular: Drugs-drug.\n\nb. Verbs were recorded as infinitive.\n\nc. Nouns with generic variability and adjectives with two endings were transcribed according to the following rules:\n\ni. If they appeared only in the feminine form, the feminine form was retained.\n\nii. If they appeared only in the masculine form, the masculine form was retained.\n\niii. If they appeared in both forms, both are retained.\n\nd. Words related to the type of study were excluded: Randomized-controlled-trials-as-topic, systematic review, etc.\n\ne. All words were converted to lower case.\n\nThe n-grams were not concatenated as in the previous word cloud, since the entirety of each article in the research corpus was loaded.\n\nCommon terms in the corpus (Figure 23):\n\n- Patients (6,260); Outcomes (5,604); Evidence (4,635): prescribing (3,558); COVID (3,355).\n\nIn order to know the general research trend of each SLR, data were extracted on the type of drugs included in each SLR if they reported it or defined as “general” if they did not mention it. It was found that 50% of the 103 SLRs addressed drugs in their general context, followed by 14% mentioning a focus on antibiotics, 8% on opioids, and 2% on generic and oncology drugs, respectively (Table 7). These 5 groups represent 77 SLRs out of the total 103. In other cases, the identified groups referred to other drug classifications or several at the same time.\n\nFinally, the central theme of each SLR was characterized in a general way and classified into 7 themes described in Figure 24.\n\n\n7. Discussion (Interpretation)\n\nIt is observed how the scientometric approach adopted for the mapping has provided a deeper understanding of the characteristics of evidence production on incentives in prescribing and dispensing of medicines and its relationship with pharmaceutical expenditure worldwide, which can be useful in decision making.26\n\nA total of 103 SLRs were analyzed, with the first published in 1998 and an average of less than 5 publications per year. Only until 2015 there is a growth to reach 6 publications in 2022. In recent years, there has been increased production on pharmaceutical expenditure, such as increases in drug prices and procurement,27 the impact on health systems28 or measures to contain it.29 More publications have been observed in recent years, which may be due to more recent publications on public health topics,30 greater innovation in the health field, or simply greater ease of publication and visualization through Internet access in recent years.\n\nWhen observing the total number of primary studies obtained in the initial search of each SLR of the research corpus, compared to the total number of primary studies included after screening and screening, it was found that less than 1% are retained, a fact produced by the heterogeneity of the studies according to the different approaches proposed by each author, or by methodological quality criteria that are excluded thanks to the rigorous systematic process of the SLR, providing reliable results for our analysis.\n\nBy not restricting the search to a single database, those that provide the highest proportion of evidence related to the search topic are identified and may be used to guide future investigations to refine the evidence. Of these, PUBMED and COCHRANE contribute more than 65% of the total SLR.\n\nAs for the representativeness of the authors, there is a high dispersion of the authors’ contributions to what Lotka’s law offers a quick panorama that indicates a low productivity, since 94% of the authors appear in a single publication. Only 6% of the total 517 authors (main or co-authors) were in average productivity, so the specialization in the field is possibly low. This fact represents a weakness compared to what has been pointed out by Lassi and Sonnenwald,30 since collaborative work offers advantages for scientific production, among others that papers with several authors can be more cited, in addition to the fact that funders encourage collaborative research, since existing resources can be optimized and also allow the transfer of knowledge and learning. This forces us to think that the research topic is an opportunity for future work.\n\nOxman A.D., is the author with the highest number of co-authorships, but by the order of signatures, as with Franklin B.D., would appear as director of the research and not as lead author. Ciaponni A. is listed as a co-author in three articles. Perhaps of the few collaborative groups that could be identified are part Grimshaw JM, Peñaloza B, Pantoja T and Herrera CA because the 4 authors are in the same 3 articles.\n\nAs for the results of the most cited publications, Horne R. was the author with the highest number of citations, followed by Smith and Shojania K.G. It is necessary to consider that citations do not necessarily correspond to the academic recognition of publications, since for example two of the publications published in 2022 did not submit citations, which can be attributed to the recent nature of the publication. Furthermore, when correlating the authors whose publications have the most citations with the country of the journal in which they are published, the United Kingdom and the United States of America are the leaders.\n\nTo find out which journals contribute most to the scientific production on the research topic, Bradford’s law allowed us to observe the behavior already described by other authors,24,31,32 in which a few journals concentrate the majority of the evidence. The 3 core journals that account for 33% of the publications are the Cochrane Database of Systematic Reviews, (UK), PloS One and PloS Medicine of the United States of America, with the same two countries at the forefront of published evidence. Similarly, when the number of publications is related to the geographical region of the journal, the western region of Europe presents the highest proportion of evidence, since the journal CDRS is part of this region and there are other journals, mainly from the British Medical Journal (BMJ).\n\nThe impact factor of the journals in which the evidence was published was expected according to the type of publications considered, since as SLR they are usually published in high impact journals, and indeed 40 of the 59 journals were classified in the first quartile (Q1) in Scimago.25 We emphasize that many journals and researchers could focus on this impact factor, which can sometimes be misused for various reasons,9 such as the obsessive search by some universities for recognition associated with publications in journals with a high impact factor or for their researchers to have high research indicators. The impact factor should be indicative and not necessarily related to the quality of the research itself, so that the provisions of the Leiden Manifesto,9 which encourages the consideration of qualitative and quantitative aspects in scientometrics and indicates that quantitative evaluation must support qualitative expert judgement, are of greater importance.33\n\nLeading countries in the publication of evidence of the research topic maintain a similar behavior to that discussed previously according to journals of publication, since in Europe it leads the United Kingdom and in America, United States of America and by relating it to the country of affiliation of the main author and the country of the publication journal, the panorama, although similar, provides additional information because authors from different countries publish mostly in journals of the United Kingdom and then in journals of the United States of America. A very small proportion of authors affiliated to institutions in the United Kingdom and the United States of America publish in journals outside their respective countries. The cause of this behavior could be inferred from a low proportion of “scientific recognition” journals, expressed, for example, as the impact factor in the countries of original affiliation of the authors, which could lead them to look for other countries of publication, a hypothesis that is supported by looking at the countries of publication of journals in which, for example, only one Latin American country appears: Brazil. This behavior has been called “parachute science” or scientific colonialism, which, due to paternalistic practices, sometimes dictates the research agendas of countries with fewer resources.34\n\nScientific colonialism is linked to modernity, globalization and this epistemic dependence on countries considered central or developed, under which models and approaches focused on the topics that in these countries can be considered relevant to research must be imposed, unable in this way to overcome the internal difficulties to position themselves from their research origin.35,36\n\nFor these reasons, it is necessary to promote research and the publication of results in other countries, including local researchers who develop their research in their context, under the conditions, environments and resources available, and thus respond to the needs they have there.\n\nPublication in countries with a tradition of generating evidence may have a cause in the type of institutions of affiliation of the author, since it is observed that about 80% of publications originate from universities and only 8% from government agencies. Therefore, it is possible that authors may decide to send their manuscripts to other countries because of studies in universities with high academic recognition or because of the desire to obtain intellectual recognition and research prestige.\n\nMoreover, to further deepen scientific colonialism, when evaluating the behavior between the country where the primary studies are developed and the country of affiliation of the main author, it is evident that the countries leading the publications include in their SLR a large number of countries of origin of the primary studies, many of them in developing countries, which is in line with research on the subject focused on colonialism in global health research, which causes local researchers of the research environments with first-hand knowledge in each country to have a limited influence on research.37 In this analysis, it is observed that they continue to lead the United Kingdom and the United States of America, followed by Canada and Australia, but new actors enter such as Malaysia, which offers a different behavior because it includes in its SLR, primary studies of the same environment in the Asian region mostly and to a lesser extent, primary studies in countries such as the United Kingdom and the United States of America (see Figure 17).\n\nThe funnel or concentration effect, which is shown by relating the country of the primary study included in the SLR, the country of main affiliation and the country of the publishing journal, shows how authors from the United Kingdom or the United States of America publish in journals from these same countries. This may be due to the increased availability of resources in these countries, which may result in funding that requires studies to be published in journals in the same country. The “advantage” offered by journals based mostly in high-income countries, as opposed to the benefit they provide, has been discussed in the analysis of how authors are increasingly required to publish in open access journals, with the associated article processing fees, and the possible exclusion of authors from low-income countries due to lack of resources.37\n\nA few cases do not follow scientific colonialism, as authors from Malaysia and Portugal published their SLRs in Turkey and the Netherlands in the first case, and in the Netherlands and Portugal in the second case, possibly because some SLRs included primary studies conducted in the same country of publication, which could make it easier for the journal to accept each article.\n\nThe likelihood of greater availability of resources in some countries is greater according to other results of this research, for example when the funding is visualized, because despite the fact that in 30% of the SLR do not report a specific source, 70% do, being in this proportion the majority exclusively governmental and national (25.25%), or in collaboration with other national or international entities or governments (15, 53%).\n\nThese proportions of funding may be due to the fact that governments in high-resource countries have more money to spend on research, which means that researchers affiliated with universities and research institutions apply for grants and may develop their studies to fit the specific doctrines and themes of global health funders, rather than the other way around.37 Only a few high-income countries, such as Switzerland, Norway, or China, were found to fund researchers with external affiliations.\n\nIt is important to note that 30% of SLRs do not report or do not receive funding, as this could be interpreted as greater independence in the judgments made, as evidence has been found that the private sector, through more direct actions such as funding researchers and universities, could threaten the independence of research. Some authors38,39 point out how the funding of private companies can negatively influence the results of research, as they may come to condition not only what is studied, but also its results.\n\nIn this research, 479 keywords were found in the 103 SLRs that were included in 67 SLRs of the research corpus. In order to know the emerging trends in the generation of evidence, we resorted to the analysis of the cooccurrence of words and found that the keywords with the highest cooccurrence are related to the central topics on which the research is focused and quickly address the trend in the generation of evidence. The results show a concentration on topics such as reimbursement, insurance, drug costs, healthcare services, healthcare personnel and, of course, healthcare spending. This confirms that knowledge and analysis of health expenditure and its financing are issues of great importance, not only for their impact on the financial sustainability of any health system, but also for the access that the population must effectively achieve,40 therefore, it is congruent that the articles included in this research mention these aspects.\n\nIn the second co-occurrence analysis on the total terms of the 103 SLRs, a total of 2,023,091 words and 78,139 unique word forms were obtained. The co-occurrence words most often refer to more specific topics, since the entire text of each article is used, and thus they appeared: Patients, Results, Evidence, Prescription and COVID; the first 4 closely related to the concepts found in the analysis by keywords and the fifth concept of COVID, appears possibly due to the avalanche of evidence that was generated related to this topic after the 2020 pandemic and that in that year reported an exponential rate of global publication around 500 publications daily,41 so it is logical that this topic affects searches that include this period as it is a new factor that enters the global pharmaceutical spending.\n\nWhen analyzing the types of drugs studied in the research corpus, about 50% of the research is found without a specific group of drugs, which suggests that it is a global issue that could then be focused on some specific types, such as antibiotics, which are a central and unique topic in 13% of the 103 SLR, possibly due to the global concern related to their rational use and microbial resistance generated by poor practices in prescribing and dispensing.42 In a smaller proportion, the SLRs whose main topic is the use of opioids, a topic of global concern on which the World Health Organization issues constant recommendations43 and which in countries such as the United States of America has generated what has been called the opioid epidemic.44,45\n\nFinally, among the topics characterized in the research corpus, the most visible are those related to financing policies, incentives and pharmaceutical interventions followed by rational use of medicines. These topics have been discussed by other researchers in the analysis of drug financing in health systems,46 including pricing policies, financing of new drugs47 and analysis of the impact that policies can have on prescribers as one of the main actors of health systems.48\n\n\n8. Conclusions\n\nThis research work achieves the fulfillment of the main objective to explore the panorama of the global scientific production of open access articles, related to the prescription and dispensing of medicines and its relationship with the pharmaceutical expenditure faced by health systems.\n\nIn this sense, the use of scientometric mapping allowed to know the trends in the generation of evidence related to the research topic, identifying the growth in annual publications since 1998, accentuated in recent years possibly by the impact that the prescription and dispensing of medicines and the consequent pharmaceutical expenditure on the sustainability of global health systems. It also allowed to visualize the most representative authors, the most cited research and publication trends according to the origin of the journal, the affiliation of the main author and the environments where the primary studies of each SLR were developed.\n\nIn general, there is a marked influence on the global scientific production on the topic of research represented by countries such as the United Kingdom and the United States, with more publications in journals and studies from these countries. The main research topics were financing policies, pharmaceutical incentives and interventions, and rational use of medicines. A scarce and worrying generation of evidence was observed mainly at the Latin American level, which may be an interesting topic for future research. As more studies from other countries can be included or developed, the results can be evaluated in different latitudes, thus contributing to the development of evidence and policies that support the sustainability of health systems and patients’ access to medicines.\n\n\n9. Strengths and limitations\n\nAlthough the results of this research are informative, some limitations inherent to the scientometric methods used are reported. First, although the search method included a large number of open access databases, which is considered a strength in terms of reproducibility and transparency of the search, the publication search algorithm specifies a restriction on identified keywords that must be present in titles or abstracts, and although it has advantages in refining the selection process, it may exclude relevant articles that are only available in restricted access or that use other keywords to refer to the research topic. Therefore, it is interesting to consider the use of other keywords and searches in paid databases to conclude whether the pattern of results is maintained or whether there are differences when using open access and restricted access information.\n\nSecond, as observed in the analysis of annual publications, since this is an evolving field of research, we may have underestimated the contribution of other recently published documents because they are not included as SLR.\n\nHowever, even with these limitations, this scientometric mapping has resulted in a broad and important global view of the research topic and its state of the art to date.\n\n\nEthical approval\n\nThis study was conducted using data retrieved from scientific evidence databases. Due to no human subjects’ involvement, ethical approval was not required.\n\n\nAuthors’ contributions\n\nConceptualization: LT, GJ, JR. Methodology: LT, GJ, JR. bibliographic search and data analysis: LT. Visualization: LT. Writing – Original Draft Preparation: LT. Writing - Review & editing: LT, GJ, JR. Supervision: GJ, JR.\n\n\nSupplementary data\n\nThere is no supplementary material in addition to that included under “data availability”.",
"appendix": "Data availability\n\nThe data associated with this article are presented in the corresponding supplementary data, located at the following link\n\nRepository name: Figshare. Checklist for “Incentives in prescribing, dispensing and pharmaceutical spending: A scientometric mapping”. DOI: https://doi.org/10.6084/m9.figshare.26948281.v2 49\n\nThis project contains the following underlying data: Luis Tocaruncho-Supplementary Material.docx. Dataset\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 Public domain dedication). For further information, please contact the authors.\n\n\nAcknowledgements\n\nThe author, Luis Hernando Tocaruncho Ariza, would like to thank the Ministerio de Salud y Protección Social de Colombia for its support in carrying out this study, which is part of the research for the Doctoral Thesis in Policy Modelling and Public Management.\n\nThe authors thank Mario Galindo of the Ministerio de Salud y Protección Social de Colombia for his contribution to the technical review.\n\n\nReferences\n\nWorld Health Organization: WHO: En el Foro de la OMS sobre medicamentos, los países y la sociedad civil presionan para lograr una mayor transparencia y precios más justos. World Health Organization; 2019. Reference Source\n\nRostamkalaee ZK, Jafari M, Gorji HA: A systematic review of strategies used for controlling consumer moral hazard in health systems. BMC Health Serv. Res. 2022; 22(1): 1260. 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Reference Source\n\nCabaluz F, Torres T: Colonialismo, dependencia y eurocentrismo: una crítica desde la periferia.Loyola M, editor. Aproximaciones al marxismo latinoamericano. Teoría, historia y política (1-). Ariadna Ediciones; 2021. Reference Source\n\nDrazer M: El largo brazo del colonialismo científico en Latinoamérica.2023, 27 octubre. Reference SourceReference Source\n\nKumar R, Khosla R, McCoy D: Decolonising global health research: Shifting power for transformative change. PLOS Global Public Health. 2024; 4(4): e0003141. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFanelli D: How Many Scientists Fabricate and Falsify Research? A Systematic Review and Meta-Analysis of Survey Data. PLoS One. 2009; 4(5): e5738. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHernández-Aguado I, Chilet-Rosell E: Investigación en salud pública: independencia y libertad académica. Revista de Bioética y Derecho. 2019; 45: 59–71. 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Publisher Full Text\n\nRojo A, Polanco A: Acceso al mercado de los fármacos innovadores financiados por el Sistema Nacional de Salud. Farmacia Profesional. 2016; 30(5): 12–15. Reference Source\n\nAbellán J, Espín J, Mestre J, et al.: Regulación de precios y financiación de nuevos medicamentos: elementos para el debate en España. Asociación de Economía de la Salud (ISBN 978-84-09-31994-7). Documentos AES. Barcelona: AES; 2021. Reference Source\n\nRashidian A, Omidvari AH, Vali Y, et al.: Pharmaceutical policies: effects of financial incentives for prescribers. Cochrane Libr. 2015; 2015(8): CD006731. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFigshare: “Incentives in prescribing, dispensing and pharmaceutical spending: A scientometric mapping” - Supplementary Material. Dataset. Figshare. 2024, September 5. Publisher Full Text"
}
|
[
{
"id": "352101",
"date": "10 Jan 2025",
"name": "Churchill Akena",
"expertise": [
"Reviewer Expertise Pharmaceutical science",
"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\nThis paper discusses the implication of scientific knowledge on the performance efficiency of health systems worldwide. The authors argue that besides the cost and availability of health commodities, other factors related to the production of scientific literature impact health systems' ability to be efficient and sustainable in the long run. With this, the authors approached the argument with a key imperative objective: “to explore the panorama of the world scientific production of Open Access articles related to the prescription and dispensing of medicines and their relationship with the pharmaceutical expenditure faced by health systems”. The authors used scientometric mapping, a “research method based on statistical and visualization methods to represent critical points and trends in a specific field” to achieve this. The authors used open-access articles without any limitations to the publication date as long they were systematic literature reviews on the “analysis of prescription, dispensing, incentives and pharmaceutical expenditure of medicines in a health care setting”. To answer their research questions, the authors used the five main stages of scientometric mapping, these include: recovery or selection of sources, migration or extraction of data, analysis, visualization, and interpretation. The authors focused on key aspects: Databases and publications, Authors, Citations, Journals and Publications, Institutions and Countries, Funders and Sponsors, Co-occurrence of terms, and Research trends. In their findings, 103 articles were considered for final analysis. Under databases and publications, the first publication to meet the topic of this article was published in 1998 and is the only article from that year. There was a hiatus of research on the topic until 2006 when another article got published. There was then a steady rise in articles from 2010 until 2022. This article found that although systematic literature reviews (SLRs) had an initial hit of over 720,000 articles, less than 1% of these are considered in the final analysis. Concerning publications, the majority of these SLRs tend to be concentrated in the top research databases like PUBMED, Cochrane, and Epistemonikos. Under authors, this study found that, out of the 517 authors considered, the majority of the authors (94%) had low productivity index (PN = 0), a few (6%) with medium productivity (PN = >0<1) and none (0%) with high productivity (PN = >1) according to the Lotka’s law of productivity of authors. Regarding authors' collaboration, this article reports that the majority (67%) of the SLRs had between three to six authors, and one article had 32 authors overall. This article reported limitations in quantifying the number of citations per author. The authors, therefore, reported the articles and country of publications contributing the most citations. They found that 80% of the citations are due to 8 articles belonging to three single authors. Conversely, the United Kingdom (UK) had the highest number of citations (2600) by country from five publications, followed by the United States (1800) from three publications. Under Journals and publications, this study found that articles were published in journals roughly following Bradford’s law which states “that the production of articles in journals presents an uneven distribution, where a high number of articles are concentrated in a small number of journals and, conversely, a small number of articles are distributed in a large number of journals”. As their findings suggest, only journals had 33.98% of the articles published, which are Cochrane, PLoS One, and BMJ Open journals. A large proportion of these publications were concentrated in the UK, with at least 50% from the Western region of continental Europe which the UK is a part of. In addition, the majority of these journals (70%) were classified as high-impact journals based on their assigned impact factor. With regards to institutions and countries, this study found that the largest proportion (80%) of the authors were university affiliates, with government entities closely following (8%). As for countries, most of the authors (>50%) were from four countries; the UK, the US, Canada, and Australia. In addition, the authors of this study further visualized the relationship between the country of the primary studies and the country of SLR for these studies. They found that the majority of primary studies cover a wider geographical area irrespective of the country of publication of the SLR. Furthermore, lead authors from the US tend to use primary studies conducted in the US for their SLR. This was not the case for authors from Qatar who tended to use primary studies from a wider variety of countries in their SLR. Under funders and sponsors, this study found that 30% of the articles reviewed did not provide information about their sponsors. For those that did, government entities were the highest proportion (25%) of the sponsors, followed by university institutions (8%). This article further characterized the country of affiliation of the sponsors and that of the authors. They found in the US and UK, authors affiliated with these countries have the same affiliation as their sponsors and funders. The authors of this article found that the most frequently mentioned terms in their review articles were Patients, Outcomes, Evidence, Prescribing, and COVID. When reviewing research trends, it was found that 50% of the studies did not mention a particle drug category whereas 14% mentioned antibiotics, 8% opioids, and 2% mentioned generic and oncology medicines.\nIn their discussion of the findings, the authors presented key arguments to enhance understanding of what their results imply. For the observed trends in the number of articles published per year, this study argues that the recent rise in the trend is due to more recent publications in public health, more innovation, and easier access to publications due to wider internet coverage. This study rationalizes that less than 1% of the initial hits of articles are considered in systematic reviews due to their rigorous nature, ensuring a more reliable result. The authors contest that low specialization is responsible for the low productivity observed according to Lotka’s productivity index for authors. They advise more collaboration among authors to improve this observation. The concentration of published literature in journals with high impact factors could be due to an obsession for recognition by some universities and researchers wanting high research indicators. The authors of this article emphasize caution when considering impact factors for the judgment of research quality. In their judgment of why most publications are in European and American journals, the authors suggest a relationship with the need to publish in high-impact journals that are coincidentally located in these countries. Furthermore, the authors suggest the need to move away from “scientific colonialism” and encourage more publication in other countries, especially if the primary researches are carried out in those countries. With regards to funding, the authors of this study rationalize that high-income countries are likely to have more income to fund studies conducted by authors affiliated with them than low-income countries. In addition, they add that the nondisclosure of funders in some studies is to avoid being judged about the possibility of their study findings being influenced by their funders, especially if the funders are private organizations. When discussing the need for the co-occurrence of terms, the authors note that these terms are related to topics on knowledge and analysis of health expenditures which are important for the financial sustainability of healthcare systems. The authors argue that the predominant mention of antibiotics is related to conservation efforts under the umbrella of antimicrobial stewardship programs enacted worldwide to curb the rise in antimicrobial resistance. Opioids are mentioned predominantly due to the deemed opioid epidemic in the US warranting regular safety updates from WHO. In conclusion, this study recognizes the importance of scientometric mapping in gathering evidence from diverse research databases globally and shaping policies that support sustainable health systems. The authors acknowledge the limitations of relying solely on open-access articles in their systematic literature review. This approach restricts the inclusion of articles that are not freely accessible and may overlook key terms not mentioned in other studies. Furthermore, the authors note that focusing on annual publications can lead to an underestimation of relevant findings.\nReviewer’s feedback\nIntroduction: In paragraph three opening sentence, the authors start by saying, “Instead of “looking for” conventional market analysis factors such as frequency and price, or those related to a holistic and etiological approach to prescribing”. This suggests that the factors discussed in this review are in contrast to those related to pricing and other causal approaches to prescribing and dispensing, which is not entirely accurate. I recommend that the authors rephrase to say, “In addition to… we delve further into…” because the other factors mentioned later, such as unfair competition, complement rather than contradict the previously discussed factors.\nMethods: The research design is appropriate for this study and the method is succinctly described to allow for the study replication. Although the study provides a clear rationale for considering only open-access articles as well as using Systematic review literature in this study, it is important to note that bias can still have a profound effect on the outcome. There is still selection bias as well as bias carried forward in the Systematic literature reviews from their primary studies which should be considered in the contexts of these findings (1). Perhaps a statement about this under the study limitations can assuage readers’ concern about this possibility as one can wonder if the results can have an entirely different picture if primary studies were included, for example.\nResults: The results are informative and backed up by the study objectives and methodology.\nDiscussions: The discussions effectively address the study's findings. The authors highlight the key results of the research. However, it is essential to consider how the number of citations can impact the perceived quality of a study. The authors mentioned that “citations do not necessarily correspond to the academic recognition of publications”. While this statement holds some truth, several factors can help someone assess the quality of a study, which in turn may lead to a higher number of citations compared to other studies. Key factors include the length and wording of the title, the choice of keywords, and the content and length of the abstract, among others. (2). It would be important for the authors to recognize this in their argument and provide a sense of direction for the readers.\nConclusions: The study concludes based on its findings and discussions. The conclusions do not overstate the significance of the findings underlined.\nOverall, I believe this study takes a definitive scientific approach to addressing the concerns outlined in the study’s objectives and questions. My concerns are minor and do not affect the scientific foundation of this research. I sincerely applaud the authors for synthesizing a vast amount of data and bringing valuable evidence to the forefront of the scientific community.\n1. Drucker et al., 2016 (Ref 2) 2. Kousha K et al., 2024 (Ref 1)\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "13229",
"date": "29 Jan 2025",
"name": "Luis Hernando Tocaruncho Ariza",
"role": "Author Response",
"response": "Title: “Incentives in prescribing, dispensing and pharmaceutical spending: A scientometric mapping. Tocaruncho-Ariza L. H, Riascos-Ochoa J, Jimenez-Barbosa W. G Dear Churchill Akena, We sincerely appreciate the careful review and constructive suggestions you have provided, which have been extremely helpful in identifying areas of improvement and enriching our work. Your detailed feedback has been crucial to optimize both the presentation and content of our article, and we deeply appreciate your thorough analysis and recognition of the contribution of the manuscript to the scientific community. In the following, we address all the raised issues and also summarize the changes made in the manuscript. Introduction: In paragraph three opening sentence, the authors start by saying, “Instead of “looking for” conventional market analysis factors such as frequency and price, or those related to a holistic and etiological approach to prescribing”. This suggests that the factors discussed in this review are in contrast to those related to pricing and other causal approaches to prescribing and dispensing, which is not entirely accurate. I recommend that the authors rephrase to say, “In addition to… we delve further into…” because the other factors mentioned later, such as unfair competition, complement rather than contradict the previously discussed factors. We fully agree with your feedback and have made the adjustment suggested in the Introduction section. We hope we have met your expectations. Methods: The research design is appropriate for this study and the method is succinctly described to allow for the study replication. Although the study provides a clear rationale for considering only open-access articles as well as using Systematic review literature in this study, it is important to note that bias can still have a profound effect on the outcome. There is still selection bias as well as bias carried forward in the Systematic literature reviews from their primary studies which should be considered in the contexts of these findings (1). Perhaps a statement about this under the study limitations can assuage readers’ concern about this possibility as one can wonder if the results can have an entirely different picture if primary studies were included, for example. We deeply appreciate your critical comments, which were essential to present the limitations of our manuscript, so we have included in the limitations section those related to selection bias and others related to literature review, highlighting the caution in generalizing the findings. Discussions: The discussions effectively address the study's findings. The authors highlight the key results of the research. However, it is essential to consider how the number of citations can impact the perceived quality of a study. The authors mentioned that “citations do not necessarily correspond to the academic recognition of publications”. While this statement holds some truth, several factors can help someone assess the quality of a study, which in turn may lead to a higher number of citations compared to other studies. Key factors include the length and wording of the title, the choice of keywords, and the content and length of the abstract, among others. (2). It would be important for the authors to recognize this in their argument and provide a sense of direction for the readers. We greatly appreciate the valuable suggestions provided in your review, and in response to your recommendation, we have included in the Discussion section some factors that affect the number of citations of a publication, thus broadening the discussion of citations for the reader to consider. Best regards, The authors, Luis Hernando Tocaruncho Ariza Javier Riascos Ochoa Wilson Giovanni Jiménez Barbosa"
}
]
},
{
"id": "352096",
"date": "15 Jan 2025",
"name": "Mosab Hammoudeh",
"expertise": [
"Reviewer Expertise Corporate finance",
"pharmaceutics and economics",
"product markets",
"corporate innovation",
"mergers and acquisitions"
],
"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 of this paper employ scientometric mapping to analyze global scientific open-access literature on prescribing and dispensing practices and their relationship with pharmaceutical expenditures in health systems. The article analyzes 103 systematic literature reviews, then provides illustrations that summarize statistics related to articles, journals, databases, key contributors, citations, institutions, countries, funders, research trends, and drug types. The United Kingdom and the United States dominate this scientific production, while Latin America, Africa and Asia show limited contributions. This last finding is attributed to the scarcity of high-impact journals in other regions. The authors introduce the term “parachute science” or “scientific colonialism” wherein researchers affiliated to institutions in leading countries publish studies conducted in other regions. They then recommend the involvement of local authors in research projects, which may better address local needs. The study provides insights for policymakers and researchers on the dynamics of pharmaceutical spending and related evidence generation. The article has several strengths. First, it follows a systematic approach with clearly defined stages (retrieval, migration, analysis, visualization, and interpretation) which improves transparency and replicability. Second, it provides a comprehensive view of the open-access literature by including 103 SLRs spanning multiple databases and countries. Third, it provides accessible representations of complex scientometric data by utilizing visualization software. Finally, the article highlights the underrepresentation of Latin America and other regions in the literature and provides actionable insights for future research. Therefore, my decision for the approval status of this article is Approved with Reservations. The following is a discussion for some of the areas in which the article can be improved:\nRepresentativeness of the sample articles. While the authors collect their articles from multiple databases, the question remains on whether open-access databases are a representative sample for the true population of articles. To illustrate this point further, I have added Table 1 below which includes statistics on pharmaceutical drug development by country. As shown in the table below, the distribution of the most productive countries by pharmaceutical drug development is similar to the distribution of the most productive countries by research publications found in this article, but with some significant differences. For example, the US is by far the most productive country by drug development where 54% of all drugs are developed within the US, whereas the UK only accounts for about 9% of all drugs developed. Moreover, China, Japan and South Korea are among the most productive drug developers, whereas they appear to have very low article publication productivity. These differences (between the distribution of countries by drug development and by research productivity) may be attributed to limitations in open-access databases. To address this comment, the authors should include a discussion on the representativeness of open-access databases and how they compare to other databases. The authors emphasize several times that this paper aims to examine the relationship of the drug prescription and dispensing literature with pharmaceutical expenditures in health systems worldwide, yet little evidence was presented directly relating to pharmaceutical expenditures, with the exception of Table 6 and Figure 21. The authors may consider rewording the introduction and study objectives to more accurately reflect the contribution of this paper, which in essence is an exploratory study that provides a detailed account for different characteristics of global pharmaceutical SLR. Limited Analysis Depth: While the scientometric mapping identifies trends, the analysis could benefit from deeper exploration of the implications of these trends on healthcare policies and practices. In otherwords, the focus on general trends without delving into specific interventions or outcomes limits its practical applicability for policymakers. For example, the authors discussed scientific colonialism, but did not provide any additional evidence that highlights the harm or shortcomings related to such an issue. Cross-Disciplinary Insights: The articles were retrieved from databases with a medical focus. Drawing connections with disciplines like economics or behavioral science could provide a richer understanding of the factors influencing prescribing behaviors. Many of the figures are too cluttered and are illegible (These are figures 2, 6, 10, 16, 17, 18 and 19). The figures are impossible to read without zooming in, and once zoomed in, the quality of the image deteriorates significantly. This is a serious problem that renders these figures as valueless. The authors should consider rethinking how they want to present these figures so that they are more legible. Here are some suggestions:\nConsider displaying a smaller number of the most important items and dropping the rest. The author already do this in several of the figures, however, they should include only the legible figure and drop the cluttered one, e.g., keep Figure 6 and drop Figure 7, keep figure 23 and drop figure 22. Consider lumping countries in the same region together to reduce the number of label, especially for countries that are less productive. For example, Jordan, Lebanon, Qatar, UAE and KSA can all be labeled as Middle East (or ME) which could help make the figures less cluttered.\n\nCorrecting Potential errors: Looking up the single article included from 1998 (Zara Yahni, 1998), the article cites 43 papers, however, Table 1 mentions that 34 total studies were included in the RSL (which I assume is a typo for SLR).\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/13-1333
|
https://f1000research.com/articles/12-477/v1
|
09 May 23
|
{
"type": "Case Report",
"title": "Case Report: Endovascular approach with kissing stent technique in aortoiliac occlusive disease (Leriche syndrome) patient",
"authors": [
"Iwan Dakota",
"Taofan Taofan",
"Suci Indriani",
"Jonathan Edbert Afandy",
"Yislam Al Jaidi",
"Suko Adiarto",
"Renan Sukmawan",
"Iwan Dakota",
"Suci Indriani",
"Jonathan Edbert Afandy",
"Yislam Al Jaidi",
"Suko Adiarto",
"Renan Sukmawan"
],
"abstract": "Background: Aortoiliac occlusive disease (AIOD) or Leriche syndrome, is a peripheral artery disease, specifically affecting the infrarenal aorta and iliac arteries. Presentation of AIOD patients ranged from asymptomatic to having limb-threatening emergencies. Advances and innovations in endovascular devices have replaced surgical approach for AIOD treatment. Here we reported a 52-year-old man presenting with AIOD managed by endovascular approach using kissing stent technique. Case presentation: A 52-year-old man, with history of chronic coronary artery disease, diabetes mellitus type 2, long-standing hypertension, and who was a heavy smoker, was admitted to our hospital with symptoms of long time with bilateral claudication and became leg rest pain. He had history of aorto-infrarenal occlusion known from previous percutaneous coronary intervention from right and left femoral artery access. Aortoiliac occlusive disease (TASC II Type D Class) diagnosis was made by lower extremity duplex ultrasound and CT angiography. The patient underwent urgent percutaneous transluminal angioplasty with kissing stent technique. The patient was discharged 4 days after the procedure without any significant complaints, received optimal medical treatment, and was educated about smoking cessation. Conclusion: Treatment of AIOD should include both modification of risk factors and efforts to increase perfusion to the lower extremities. An endovascular approach is an excellent alternative and may replace surgical approach in complex aortoiliac obstructive disease. In this case report, an endovascular approach with kissing stent technique showed good results for the patient.",
"keywords": [
"aortoiliac occlusive disease",
"Leriche syndrome",
"TASC D",
"endovascular therapy",
"percutaneous transluminal angioplasty",
"kissing stent"
],
"content": "Introduction\n\nAortoiliac occlusive disease (AIOD), also known as Leriche syndrome results from a chronic occlusive process of the infrarenal aorta and iliac arteries and is the leading cause of peripheral arterial disease (PAD). Epidemiological studies about PAD including AIOD and infrainguinal artery disease has reported that most patients presented with multistage disease. PAD is rare under the age of 50 years, increasing to about 20% by age 60 years and over 40% by age 85 years. An ankle brachial index (ABI) lower than 0.9 is used to diagnose PAD in clinical practice and epidemiologic studies, to identify both symptomatic and asymptomatic patients.1,2\n\nRisk factors for AIOD include hypertension, hyperglycemia, hyperlipidemia, nicotine use, age, sex, and family history. AIOD patients generally present with a classic triad of clinical symptoms: (1) claudication of lower extremities, (2) impotence, and (3) weak/absence of femoral pulse. Diagnosis of AIOD is made with CT angiography or conventional angiography. Angiography was used to determine the location of the obstruction, length, collateral circulation, and distal patency.1,3\n\nAdvances and innovations in endovascular devices have replaced standard surgical approach with endovascular approach, including in long and complex lesions. An endovascular approach is currently recommended as the definitive interventional treatment for AIOD. Endovascular treatment performed in the aortoiliac segment has resulted in good technical success, low complication rates compared with standard surgery, and offers great patency. Endovascular approach in Trans-Atlantic Inter-Society Consensus (TASC) C and D aortoiliac lesions should be considered as an alternative to the standard surgical approach.4 Here we report a 52-year-old man presenting with AIOD or Leriche syndrome and managed by an endovascular approach using a kissing stent technique in the National Cardiovascular Center Harapan Kita, Jakarta, Indonesia.\n\n\nCase report\n\nA 52-year-old Javanese man was referred to our hospital with a history of chronic coronary artery disease, type 2 diabetes mellitus, long-standing hypertension, and who was a heavy smoker. He had symptoms of worsening bilateral leg pain, and felt chest pain sometimes, especially when he was walking for long distances. Another clinical symptom that he had was impotence. The patient had a history of aorto-infrarenal occlusion that was known when he underwent percutaneous coronary intervention (PCI) via the right radial artery but failed after the approach was moved to both sides of femoral artery access because of the occlusion in bilateral common iliac arteries. His previous medication was aspilet 80 mg once daily, clopidogrel 75 mg once daily, rivaroxaban 15 mg once daily, bisoprolol 2.5 mg once daily, isosorbide mononitrate 2.5 mg twice a day, candesartan 16 mg once daily, simvastatin 20 mg once daily and novorapid 3×16 IU sub cutaneously before meals.\n\nPhysical examination showed blood pressure 160/86 mmHg, HR 68 bpm, RR 18 breaths per minute, temperature 36°C. Normal cardiac, abdominal, and extremity examinations. ECG showed sinus rhythm. Chest radiograph revealed cardiomegaly (65% of cardio thoracic ratio (CTR)) and aorta elongation. Laboratory examination was within normal limits. Lower extremity duplex ultrasound (DUS) suspected significant stenosis of the abdominal aorta at the infra-renal level, no thrombus in the deep veins in both limbs, and positive arterial flow to distal to both legs. Right ABI was 0.42 and left was 0.35, right toe brachial index (TBI) was 0.45 and left 0.49. Lower extremity CT scan angiography (CTA) showed infrarenal abdominal aortic occlusion from aortic bifurcation, to bilateral common iliac artery and causes suspected thrombus, intermittent atherosclerosis of the abdominal aorta, arterial vasculature of both extremities filled distally, no stenosis or occlusion was seen (Figure 1).\n\nThe patient was diagnosed with chronic limb ischaemia (type D TASC Classification) causing bilateral aortic infrarenal–iliaca occlusion (Leriche syndrome). The patient was planned to undergo urgent percutaneous transluminal angioplasty (PTA). He got Enoxaparin 60 mg sub cutaneously twice per day, some additional anti-hypertension therapy, and other previous drugs were continued.\n\nDuring initial aortography, total occlusion was found in the abdominal aorta from infrarenal the aortoiliac bifurcation until bilateral common iliac arteries (Figure 2B). Several balloon pre-dilations were performed on right and left iliac arteries (Figure 2C and D). Then, aortography was performed again and showed positive flow on both right and left femoral arteries (Figure 2E). Insertion of 12×95×100 mm bifurcated stent graft extension (Seal®, S&G Biotech, Korea) from the right femoral artery access and 12×75×80 mm bifurcated stent graft extension (Seal®, S&G Biotech, Korea) from the left femoral artery access were done (Figure 2F). Dilatation of the stents was performed with a kissing stent technique using two balloons (Mustang®, Boston Scientific, MA, US) (Figure 2G). The final result of the procedure was positive flow until distal part of both common femoral arteries (Figure 2H).\n\nAfter the procedure, the patient was observed in the intermediate ward. Lower extremity DUS didn’t find any pseudoaneurysm/AV fistula in the right-left femoral region nor deep vein thrombus in both legs, arterial flow was positive to distal of both legs. Plethysmography results were: right ABI 0.8 and left 0.77, right TBI 0.75 and left 0.74. Lower extremity CTA revealed patent kissing stent graft at bilateral common iliac artery, positive flow to bilateral femoral artery, bilateral subpopliteal artery, until bilateral malleolus region especially left anterior tibial artery and right posterior tibial artery. Other contrast flow was improved compared to pre-PTA (Figure 3). The patient was discharged 4 days after the procedure without any significant complaints, continued his previous medication, and was educated about smoking cessation.\n\n\nDiscussion\n\nDefinitive treatment approaches to AIOD have changed in recent years. Inter-Society Consensus for the Management of Peripheral Arterial Disease suggested that AIOD patients with TASC C and D classification are preferred for surgical treatment, but there has been a shift in the recent guidelines by the European Society of Cardiology and of the European Society for Vascular Surgery suggested that endovascular-first strategy may be considered for AIOD for patient with severe comorbidities and if done by an experienced team.5,6 Endovascular therapy is a less invasive treatment option and may reduce morbidity. Patients with extensive AIOD could be treated using endovascular techniques with 86% to 100% of the patients' technical success rates.7 Another recent study by Dong et al.8 evaluated uninterrupted patency of the treated lesion until 5 years follow-up of AIOD patient treated with endovascular approach was as high as 91.3% and 100% restored blood flow through the original target lesion.\n\nAlthough several studies have analyzed factors that may affect long-term patency after endovascular treatment of AIOD, including stent placement, lesion morphology, and outflow, there is no consensus currently on the risk factors associated with restenosis after endovascular intervention in patients with AIOD.9 A randomized trial comparing primary versus selective stenting for AIOD showed similar long-term patency in both groups, with lower costs in the selective stenting group.10 Nevertheless, most studies for extensive aortoiliac lesions preferred primary stenting. The argument for primary stenting was that stenting without predilatation (direct stenting) reduced the risk of not only vessel rupture but also distal embolism.9 A study by AbuRahma et al.11 showed that selective stenting was associated with reduced clinical success in long lesions and that primary stenting should be the option for all TASC C and D lesions. In our case, we preferred to do the primary stenting because of presented with TASC D lesion.\n\nTegtmeyer was the first to describe bilateral simultaneous balloon angioplasty, known as kissing balloon technique, as a potential endovascular treatment for bilateral proximal common iliac artery stenoses or focal aortic bifurcation.12 However frequent complications occurred, such as dissections and poor angiographic and/or hemodynamic outcomes. Later, the repair of the aortic bifurcation using concurrently placed bilateral stents, known as kissing stents technique, was documented. This made the majority of aortoiliac atherosclerotic lesions amenable to percutaneous therapy.13 Systematic review by Jebbink et al.14 revealed that the use of kissing stent technique in AIOD had a 98.7% success rate, 10.8% complication rate, 89.9% clinical improvement achieved in 30 days, and 89.3%, 78.6%, and 69.0% primary patency rate at 12, 24, and 60 months respectively. According to the stent type, Sabri et al.15 mentioned that for atherosclerotic aortic bifurcation occlusive disease, covered balloon-expandable kissing stents have greater patency at 2 years compared to bare metal balloon-expandable stents. We used kissing stent technique with covered balloon-expandable stent and showed a very good result. Despite improved blood flow in short-term follow-up by CT scan and duplex ultrasound, long-term follow-up needs to be done for the patient.\n\nPatients with PAD, including those with AIOD, should receive treatment that addresses two different components. First is the risk associated with a particular lesion as mentioned before and second is the aspects related to increased risk of any cardiovascular events. Best pharmacological therapy, as well as nonpharmacological treatment such as smoking cessation, healthy diet, weight loss, and regular physical exercise, should be achieved.6 In our case, the patient was a heavy smoker, but he admitted that he just committed to stop smoking. Unfortunately, he had long-standing hypertension and type 2 DM which also were another important risk factor of atherosclerosis process itself. Good teamwork between care provider, patient, and patient’s family should be targeted in this scenario.\n\n\nConclusion\n\nWe had presented a case of a patient with AIOD (Leriche syndrome) TASC II type D which successfully underwent endovascular approach (kissing stent technique) with a good result and blood flow improvement to distal area of lower extremity. Endovascular management of TASC II type C and D lesions approach is an excellent alternative to the surgical approach. Despite that, CV risk modification also has a pivotal role.\n\n\nResearch ethics and patient consent\n\nWritten informed consent has been obtained from the patient for publication of the case report and accompanying images.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nAcknowledgements\n\nWe would like to thank the patients for allowing us to have their cases published.\n\n\nReferences\n\nKashou AH, Braiteh N, Zgheib A, et al.: Acute aortoiliac occlusive disease during percutaneous transluminal angioplasty in the setting of ST-elevation myocardial infarction: a case report. J. Med. Case Rep. 2018; 12(1): 6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBuckley B, Holden A, Merrilees S, et al.: 13 - Revascularization: Aortoiliac.Mauro MA, Murphy KP, Thomson KR, et al., editors. Image-Guided Interventions. Boston: Elsevier; (Third Edition). 2020 (cited 2023 Feb 20); pp. 99–110.e2. (Expert Radiology). Publisher Full Text Reference Source\n\nRodríguez SP, Sandoval F: Aortoiliac occlusive disease, a silent syndrome. BMJ Case Rep. CP. 2019; 12(7): e230770. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTaha AA, Hefnawy ET, Tawfik AR, et al.: Endovascular management of Trans-Atlantic Inter-Society Consensus C and D aortoiliac occlusive disease as a feasible, effective, and durable intervention. Egypt J. Surg. 2017; 36(4): 401. Publisher Full Text\n\nNorgren L, Hiatt WR, Dormandy JA, et al.: Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J. Vasc. Surg. 2007; 45(1): S5–S67. Publisher Full Text\n\nAboyans V, Ricco JB, Bartelink MLEL, et al.: 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO) The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur. Heart J. 2018; 39(9): 763–816. PubMed Abstract | Publisher Full Text\n\nJongkind V, Akkersdijk GJM, Yeung KK, et al.: A systematic review of endovascular treatment of extensive aortoiliac occlusive disease. J. Vasc. Surg. 2010; 52(5): 1376–1383. PubMed Abstract | Publisher Full Text\n\nDong X, Peng Z, Ren Y, et al.: Endovascular treatment of aorto-iliac occlusive disease with TASC II C and D lesions: 10 year’s experience of clinical technique. BMC Cardiovasc. Disord. 2023; 23(1): 71. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang M, Zhang B, Niu G, et al.: Long-term results of endovascular reconstruction for aortoiliac occlusive disease. Quant. Imaging Med. Surg. 2021; 11(4): 1303–1312. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlein WM, van der Graaf Y , Seegers J, et al.: Dutch Iliac Stent Trial: Long-term Results in Patients Randomized for Primary or Selective Stent Placement. Radiology. 2006; 238(2): 734–744. Publisher Full Text\n\nAbuRahma AF, Hayes JD, Flaherty SK, et al.: Primary iliac stenting versus transluminal angioplasty with selective stenting. J. Vasc. Surg. 2007; 46(5): 965–970.e2. PubMed Abstract | Publisher Full Text\n\nTegtmeyer CJ, Kellum CD, Kron IL, et al.: Percutaneous transluminal angioplasty in the region of the aortic bifurcation. The two-balloon technique with results and long-term follow-up study. Radiology. 1985; 157(3): 661–665. Publisher Full Text\n\nSharafuddin MJ, Hoballah JJ, Kresowik TF, et al.: Kissing Stent Reconstruction of the Aortoiliac Bifurcation. Perspect. Vasc. Surg. Endovasc. Ther. 2008 Mar 1; 20(1): 50–60. Publisher Full Text\n\nJebbink EG, Holewijn S, Slump CH, et al.: Systematic Review of Results of Kissing Stents in the Treatment of Aortoiliac Occlusive Disease. Ann. Vasc. Surg. 2017; 42: 328–336. PubMed Abstract | Publisher Full Text\n\nSabri SS, Choudhri A, Orgera G, et al.: Outcomes of Covered Kissing Stent Placement Compared with Bare Metal Stent Placement in the Treatment of Atherosclerotic Occlusive Disease at the Aortic Bifurcation. J. Vasc. Interv. Radiol. 2010; 21(7): 995–1003. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "252298",
"date": "25 May 2024",
"name": "Yopie Afriandi Habibie",
"expertise": [
"Reviewer Expertise Cardiovascular",
"Vascular & Endovascular Surgery",
"Vascular Medicine",
"Thoracic Trauma",
"Trauma",
"Stem Cell",
"Cardiac Surgery",
"Thoracic 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\nCase Report: 1. Please describe the duration of the symptoms and the specific symptoms experienced by the patient during the course related to the AIOD. 2. Can you provide more specific details about the vascular examination related to AIOD? 3. In the third paragraph, please correct the diagnosis to Chronic Limb Threatening Ischemia (TASC II Type D lesion). 4. In the fifth paragraph, please explain how you performed initial orthography in this patient, despite an AIOD? Did you puncture both sides of the Femoral artery? Please explain step by step the procedure before implanting the kissing stent. Also, which wire did you use to penetrate the lesion? For balloon pre-dilatation, which Fr did you use (Fig 2C and D)? 5. Regarding Fig 2H, do you have another image after the final result showing the stent's patency?\nDiscussion 1. Paragraph two last sentence: Please explain your reasoning for choosing primary stenting over selective stenting despite the risks.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "11830",
"date": "04 Jul 2024",
"name": "Taofan Taofan",
"role": "Author Response",
"response": "Thank you for the constructive insight into our article. Here we try to answer and revise some of the questions and notes from the reviewer. Case Report: 1. Please describe the duration of the symptoms and the specific symptoms experienced by the patient during the course related to the AIOD. The patient experienced the symptomps in the past year and his PCI was done one year earlier. 2. Can you provide more specific details about the vascular examination related to AIOD? Lower extremity duplex ultrasound (DUS) suspected significant stenosis of the abdominal aorta at the infra-renal level with high end-diastolic monophasic doppler curve in both external iliac artery and common femoral artery, rounded doppler curve in both popliteal, anterior, and posterior tibial artery, no thrombus in the deep veins in both limbs, and positive arterial flow to distal to both legs. Pletismography examination revealed Rright ABI was 0.42 and left was 0.35, right toe brachial index (TBI) was 0.45 and left 0.49. 3. In the third paragraph, please correct the diagnosis to Chronic Limb Threatening Ischemia (TASC II Type D lesion). The diagnosis has been revised into chronic limb threatening ischaemia (TASC II type D lesion) causing bilateral aortic infrarenal–iliaca occlusion (Leriche syndrome). 4. In the fifth paragraph, please explain how you performed initial orthography in this patient, despite an AIOD? Did you puncture both sides of the Femoral artery? Please explain step by step the procedure before implanting the kissing stent. Also, which wire did you use to penetrate the lesion? For balloon pre-dilatation, which Fr did you use (Fig 2C and D)? A more detailed step by step procedure with the device used has been described in the paragraph. 5. Regarding Fig 2H, do you have another image after the final result showing the stent's patency? We have changed the Fig 2H, hope it can show clearer image of the final result. Discussion 1. Paragraph two last sentence: Please explain your reasoning for choosing primary stenting over selective stenting despite the risks. In our case, we preferred to do the primary stenting for a better long term clinical succes and patency since our patient was presented with extensive aortoiliac lesions (TASC II type D lesion). Once again thanks to Dr. Yopie Afriandi Habibie for the time and effort in reviewing our article, please let us know if further revision is needed."
}
]
}
] | 1
|
https://f1000research.com/articles/12-477
|
https://f1000research.com/articles/13-1329/v1
|
06 Nov 24
|
{
"type": "Research Article",
"title": "Assessing the students’ evaluations of educational quality (SEEQ) questionnaire in Oman higher education",
"authors": [
"Muna Al Kalbani"
],
"abstract": "Background One of the most popular tools that is used to evaluate education quality is the Student Evaluation of Education Quality (SEEQ). This local data study examined the SEEQ’s psychometric properties in Omani education, specifically its validity and reliability.\n\nMethods This was quantitative research to assess educational quality from the students’ viewpoint. The study was conducted at Muscat College from January to March 2024.Simple randomization implemented at the course level helped to choose the participants. All students registered in the specified courses were asked to take part after a random sample of the courses Muscat College offers throughout the study term was chosen. Five hundred fifty students completed the survey. AMOS was used to conduct confirmatory factor analysis (CFA), and PSS was used to evaluate the internal consistency (IBM Corp., 2024a, 2024b).\n\nResults CFA of the SEEQ indicated that the eight -factor solution best fit the data. Results also showed that the SEEQ has overall good-to-excellent reliability. The adapted scale was psychometrically sound, proving SEEQ’s applicability\n\nConclusions This study proposes using SEEQ to measure Oman’s education quality.",
"keywords": [
"SEEQ",
"Student Evaluations of Teaching (SET)",
"validity",
"reliability",
"teaching"
],
"content": "1. Introduction\n\nCourse and program evaluation is a quality control process performed internally by all colleges and universities. Student evaluations of teaching (SET) are performed by delivering questionnaires that employ rating scales, such as the Likert scale. These scales enable students to indicate their degree of either agreeing or disagreeing with certain statements. While SETs were originally designed for evaluating courses and programs, they have since been used to assess teaching effectiveness. Various teaching aspects, including group interaction, preparation and organization, and student feedback, are often evaluated when evaluating the effectiveness of a teacher (Constantinou & Wijnen-Meijer, 2022). The data collected through SETs can provide valuable insights into the need for modifying the instructional material or teaching approach used in a specific course. SETs have also been utilized to assist make valuable decisions on the development of academic careers. Prospective faculty members are frequently asked by institutions to supply their Student Evaluation of Teaching (SET) outcomes from previous institutions as a requirement of their application for a new position. This requirement greatly impacts the professional progression of faculty members, both within their current institution and when seeking job opportunities outside (Constantinou & Wijnen-Meijer, 2022).\n\nEvaluation tools provide a way for individuals to enhance and assess the standard of education. In these days, instruments are frequently employed in educational research, especially when students assume the role of assessors. Marsh’s (1982) The SEEQ is one of the most popular SET tools used in the education sector. It has been employed in many locations, including higher learning institutions in multiple nations (Grammatikopoulos et al., 2015). SEEQ has been developed with a comprehensive consideration of the various facets of teaching and learning, enabling its applicability across all academic disciplines. It is widely used worldwide and considered one of the most accurate and useful measures to measure teaching effectiveness (Al-Muslim & Arifin, 2015). Marsh (1982) discovered that the SEEQ scale displayed internal consistency within the range of 0.88 to 0.97 in the United States. In Australia, the utilization of SEEQ resulted in an internal consistency level of 0.89, as reported by Marsh and Roche in 1993. In a study conducted in Oman in 2011, Cronbach’s alpha value of 0.87 was reported by Al-Hinai. SEEQ has shown positive psychometric results across various linguistic and cultural contexts, yet, it has not yet been administered to college students in Oman. Based on the researcher’s knowledge, no previous studies have examined the psychometric properties of the SEEQ questionnaire among colleges and universities students in Oman. This study aims to investigate the psychometric properties of the SEEQ among college students in Oman, so as to fill a research gap. Specifically, the goals of this study are as follows: (a) Evaluate the reliability of the Arabic version of SEEQ, and (b) Find out how many dimensions it has by using confirmatory factor analysis.\n\n\n2. Methods\n\nThe Students’ Evaluations of Educational Quality (SEEQ) Questionnaire (Marsh & Roche, 1993) is used in this quantitative research to assess educational quality from the students’ viewpoint. The study was conducted at Muscat College from January to March 2024.\n\nCollecting numerical data for statistical analysis is a fundamental aspect of the quantitative technique, facilitating the identification of correlations and patterns within the dataset (Creswell & Creswell, 2017). The research aimed to contribute to the broader discourse on assessing higher education by gathering data on student evaluations of course quality (Hancock & Algozzine, 2016).\n\nA total of 278 students are needed to be surveyed to achieve a 95% confidence interval, a 5% significance level, and 80% power. The participants were selected by a simple randomization process. The participants were chosen through a simple randomization process at the course level. Completion is based upon checking the registration department for a comprehensive list of Muscat College students. Simple randomization implemented at the course level helped to choose the participants. All students registered in the specified courses were asked to take part after a random sample of the courses Muscat College offers throughout the study term was chosen. Five hundred fifty students completed the survey. The response rate was 91.7%, with 550 out of 600 individuals participating.\n\nIn the current study, 550 students from three different departments at Muscat College participated by completing the questionnaires (SEEQ) distributed to them. The participants averaged 20 years old, with a 2.54-year standard deviation.\n\nThe ethical approval was received by Muscat College’s Research Ethical Committee under the reference MC/RC/1/2024, dated January 2024. Prior authorization was obtained before starting the search. Because the study only required completing a non-invasive, anonymous survey (SEEQ) measuring student assessments of educational quality, which had been approved by the research committee, all participants provided oral permission before they were contacted. Participants were told that their participation in this research was founded on the principles of confidentiality and autonomy, and that they might withdraw from the study at any moment.\n\nThe Students’ Evaluations of Educational Quality (SEEQ) Questionnaire was used for data collecting; the chosen sample of students received paper-based questionnaires. The scheduled hour for the questionnaire administration was set; the teacher stayed outside the classroom to provide an objective environment while students were completing the surveys. Following completion of the surveys, a chosen student collected them, sealed them in an envelope, and handed the envelope to the authors. Students were advised that the teacher would not get any direct comments from the assessments, therefore ensuring the privacy of their answers. Three months, from January 2024 to March 2024, defined the data collecting period. Following the ethical standards set by the college, all completed surveys accompanied with signed informed permission forms.\n\nThe Students’ Evaluations of Educational Quality (SEEQ) questionnaire was the tool used (Marsh, 1982). The SEEQ consists of thirty items that measure eight dimensions under consideration, one of which measures the subject’s overall evaluation. The SEEQ consists of the following dimensions: breadth of coverage, assessment, assignments, learning value, teacher enthusiasm, organization, group interaction, individual rapport, and overall rating (Marsh, 1982). Each component is rated on a five-point Likert scale: strongly disagree, disagree, neutral, agree, and strongly agree (Marsh, 1982). The tool’s developer, Professor Herbert March, was contacted personally and granted permission to be used for study (Marsh, 1982). The author translated SEEQ into Arabic prior to the study, and the instrument was then translated back into English by a bilingual expert who has experience in this area.\n\nDiscrepancies that were identified were rectified in the Omani version of the instrument after the bilingual expert and the authors conducted a comparison between the two editions of the instrument (the original and the re-translated version). Subsequently, a preliminary test was administered to a selected group of students and colleagues to evaluate the reliability of the translated SEEQ. Modifications were implemented to improve the semantic significance of some words in Arabic.\n\nThe SEEQ scale was validated using a combination of alternate methods and data analysis. An evaluation of the internal consistency of the scale and its three subscales was conducted using Cronbach’s alpha statistics. The structure of the SEEQ factors was examined using confirmatory factor analyses (CFAs) in AMOS v26, which is a structural equation modeling program. The model was evaluated using fit indices that are often used in the discipline (Blunch, 2008). The Tucker-Lewis index (TLI), goodness-of-fit index (GFI), comparative fit index (CFI), and Chi-Square (χ2) are among the measures. Fit indices of CFI, GFI, and TLI exceeding 0.90 and RMSEA below 0.08 are generally considered acceptable (Bentler, 1990).\n\n\n3. Results\n\nTo determine the internal consistency reliability of each SEEQ scale, Cronbach’s alpha was used. The output was assessed using the corrected item-total correlation or alpha if an item was omitted (Field, 2013). The reliability (alpha) coefficients for the eight 30-item SEEQ scales are presented in Table 1.\n\nConfirmatory factor analysis (CFA) is the most suitable technique for cross validating the factor structure of a test, as per Byrne (2001). Using the AMOS version 26.0 statistical tool, a covariance matrix (Figure 1) was used to evaluate the validity of the item allocation to the eight SEEQ measures (IBM Corp, 2024a). The eight-factor structure proposed for the original scale has been confirmed by the Arabic version of SEEQ’s acceptable CFA indices (Figure 1).\n\n\n4. Discussion\n\nThe revised CFA model’s goodness-of-fit indices indicate a strong fit to the study data: χ2 (df =349) = 3854.401, CFI = .963, GFI = .970, PCOLOSE = 1.00, and RMSEA = .032. These indices all exceeded thresholds. Cronbach’s Alpha showed 0.935 reliability, demonstrating high internal consistency. The findings support using SEEQ to evaluate educational programs and courses in Oman in the future using similar samples. Because of the small sample size, more research is required to replicate the current study with bigger and more varied samples in order to apply the findings to Oman’s higher education students. This study showed SEEQ’s applicability in Oman’s higher education. Individual Oman instructors may use the SEEQ for gathering student feedback on their instruction and modules.\n\nThe ethical approval was received by Muscat College’s Research Ethical Committee under the reference MC/RC/1/2024, dated January 2024. Prior authorization was obtained before starting the search. The nature of the research and the little risk involved led to oral consent instead than written permission. Participants in the research had to complete a non-invasive, anonymous survey (Students’ Evaluations of Educational Quality - SEEQ), which only gauges their opinions of educational quality. Written consent was believed to be not required given the low-risk nature of the survey and its anonymous form. The research committee authorized the oral consent procedure as well as the SEEQ tool. All participants provided oral permission before they were contacted. Participants were told that their participation in this research was founded on the principles of confidentiality and autonomy, and that they might withdraw from the study at any moment.\n\nAll participants gave informed consent to be interviewed orally. The college’s ethics committee accepted this method. The source of the informants was who agreed that the data were provided for research purpose and that the data can be published. They also consented that the data were provided for research anonymously without having distorted scientific meaning.\n\nI declare that the data provided is true and can be accounted for.",
"appendix": "Data availability\n\nFigshare: Data 1_1 - Copy.xls https://doi.org/10.6084/m9.figshare.26494288.v2 (Al-kalbani, 2024a).\n\nThis project contains the following underlying data:\n\n• Data 1_1 - Copy.xls\n\nData are available under the terms of the Creative Commons Zero (CC0)\n\nAll data has been deidentified using the Safe Harbour approach, therefore assuring ethical norms’ conformance. Among the authors who helped to produce this dataset was Muna Alkalbani.\n\nFigshare: SEEQ-Arabic version.pdf https://doi.org/10.6084/m9.figshare.27222894.v5 (Al-kalbani, 2024b).\n\nThis project contains the following extended:\n\n• ilovepdf_merged (3).pdf\n\nData are available under the terms of the Creative Commons Zero (CC0)\n\n\nReferences\n\nAl-Muslim M, Arifin Z: The usability of SEEQ in quality evaluation of Arabic secondary education in Malaysia. Int. Educ. Stud. 2015; 8(3): 202–211.\n\nAl-Kalbani M: Data 1_1 - Copy.xls. Dataset. figshare. 2024a. Publisher Full Text\n\nAl-Kalbani M: SEEQ-Arabic version.pdf. figshare. Figure. 2024b. Publisher Full Text\n\nAl-Muslim M, Arifin Z: The Usability of SEEQ in Quality Evaluation of Arabic Secondary Education in Malaysia. Int. Educ. Stud. 2015; 8(3): 202. Publisher Full Text\n\nBentler PM: Comparative Fit Indexes in Structural Models. Psychol. Bull. 1990; 107(2): 238–246. Publisher Full Text\n\nBlunch N: Introduction to Structural Equation Modeling Using SPSS and AMOS. Los Angeles: Sage Publication; 2008.\n\nByrne BM: Structural Equation Modeling with AMOS: Basic Concepts, Applications, and Programming. Mahwah, NJ: Lawrence Erlbaum Associates; 2001.\n\nConstantinou C, Wijnen-Meijer M: Student evaluations of teaching and the development of a comprehensive measure of teaching effectiveness for medical schools. BMC Med. Educ. 2022; 22(1): 113. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCreswell JW, Creswell JD: Research Design: Qualitative, Quantitative, and Mixed Methods Approaches. Sage Publications; 2017.\n\nField A: Discovering Statistics Using IBM SPSS Statistics. Sage Publications; 2013.\n\nGrammatikopoulos V, Linardakis M, Gregoriadis A, et al.: Assessing the Students’ Evaluations of Educational Quality (SEEQ) questionnaire in Greek higher education. High. Educ. 2015; 70(3): 395–408. Publisher Full Text\n\nHancock DR, Algozzine B: Doing Case Study Research: A Practical Guide for Beginning Researchers. Teachers College Press; 2016.\n\nIBM Corp: IBM SPSS Amos for Windows, Version 29.0. Armonk, NY: IBM Corp; 2024a.\n\nIBM Corp: IBM SPSS Statistics for Windows, Version 29.0. Armonk, NY: IBM Corp; 2024b.\n\nMarsh HW: SEEQ: A Reliable, Valid, and Useful Instrument for Collecting Students’ Evaluations of University Teaching. Br. J. Educ. Psychol. 1982; 52(1): 77–95. Publisher Full Text\n\nMarsh HW, Roche L: The Use of Students’ Evaluations and an Individually Structured Intervention to Enhance University Teaching Effectiveness. Am. Educ. Res. J. 1993; 30: 217–251. Publisher Full Text"
}
|
[
{
"id": "344928",
"date": "20 Dec 2024",
"name": "Margret Sigrun Sigurdardottir",
"expertise": [
"Reviewer Expertise Higher Education teaching and learning",
"Scholarship of teaching and learning",
"qualitative 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\nThank you for the opportunity to review the article Assessing the students’ evaluations of educational quality (SEEQ) questionnaire in Oman higher education. The article discusses the use of Student Evaluation of Teaching (SET) tools, particularly the SEEQ, to assess teaching effectiveness and evaluate courses and programmes. While the topic is significant and timely, the authors fall short in addressing critical issues surrounding SET's broader use and the nuances involved in its application. The authors claim that while SET was originally designed to evaluate courses and programmes, it has since been repurposed to assess teaching effectiveness. However, this statement is presented without any supporting references. It would strengthen the article to provide evidence explaining how a tool intended for course evaluation has been adapted to measure teaching effectiveness and the mechanisms through which this occurs.\nA related point concerns the citation of Constantinou & Wijnen-Meijer (2022). While the paper is referenced to substantiate the claim that SET evaluates various aspects of teaching, the authors neglect to engage with the controversial aspects raised in the same work. For example, there is no discussion of the criticism surrounding SET, such as its potential biases or limited reliability in assessing teaching quality. This omission becomes particularly pronounced when the authors assert that SET has been used to support valuable decisions in academic career development—a statement that is neither referenced nor critically examined.\nThe authors state that SEEQ is widely used worldwide and is regarded as one of the most accurate and useful tools for measuring teaching effectiveness. However, this sweeping assertion is supported by a single citation that discusses the SEEQ's usability in evaluating quality within Arabic secondary education in Malaysia. The reliance on this narrow context does not justify claims of global applicability or general reliability. A more nuanced review of SEEQ's strengths and limitations across varied educational settings would provide greater validity to this argument.\nThe methods section lacks sufficient detail on the selection of courses evaluated using the SEEQ. For instance, the authors do not provide information on the diversity of subjects, course sizes, or academic years represented in the sample—all of which could significantly influence the SET results. Including such details topic would enable readers to assess the generalisability and robustness of the findings.\nAdditionally, the discussion on SEEQ’s application to programmes versus individual courses is inconsistent. The authors emphasise SEEQ's use in evaluating education programmes but later recommend its application for individual instructors seeking feedback on modules. This raises questions about the scope and intended purpose of the SEEQ in the context of Oman’s higher education system. The need for further research is also highlighted, but the rationale for this call is unclear. Specifically, the authors suggest that more varied samples are needed to generalise findings to Omani students, yet they simultaneously endorse SEEQ's utility for evaluating programmes. This contradiction requires clarification.\nThe consent statement asserts that participants gave informed oral consent to be interviewed. However, the article does not present any interview data, which renders this inclusion confusing. Further, the sentence describing participant consent—“The source of the informants was who agreed that the data were provided for research purpose and that the data can be published…”—is poorly written and lacks coherence. It should be rephrased for clarity and accuracy. The references list exhibits inconsistencies, with some citations appearing twice and formatting varying between bolded and highlighted titles. Ensuring adherence to a consistent citation style would improve the article’s professional presentation.\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": []
},
{
"id": "347907",
"date": "02 Jan 2025",
"name": "Dickson Okoree Mireku",
"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\n1.\n\nClarity and Accuracy of Presentation and Citation of Current Literature The introduction does not reference relevant literature, citing only a few sources such as Al-Muslim and Arifin (2015) and Constantinou and Wijnen-Meijer (2022). This is because authors failed to adequately connect the literature about students appraisal or evaluation of teaching performances (presumably what the authors aimed to review) about the context of higher education in Oman. This limitation will affect the discussion of the work as the authors may not have the opportunity to thoroughly discuss the findings of the study in relation to the reviewed literature. In this regard, the literature review needs to be more extensive to strengthen the conceptual and theoretical foundation of the work.\nTo enhance the study, the following literature areas should be reviewed: a)\n\nThe role of student evaluations in assessing teaching effectiveness and educational quality. b)\n\nCross-cultural validation and adaptation of psychometric tools in higher education. c)\n\nReliability and validity of the SEEQ questionnaire across different contexts. d)\n\nBest practices for using student evaluations to improve instructional methods. e)\n\nChallenges and implications of implementing SETs in higher education institutions in the Middle East. There is a lack of seamless transition between the global applications of SEEQ and its specific implementation in Oman, resulting in a disjointed narrative. Many cited studies are relatively old, and incorporating more recent literature could enhance the relevance of the discussion.\n2.\n\nStudy Design Appropriateness and Academic Merit a)\n\nWhile a quantitative approach is employed, the justification for selecting this methodology over alternatives for evaluating the psychometric properties of SEEQ is not provided. b)\n\nThe sampling method is outlined, but it does not clarify the rationale behind choosing Muscat College and its three departments, limiting the broader relevance of the results. c)\n\nAlthough ethical considerations are acknowledged, the write-up lacks specifics on how anonymity and data protection were maintained beyond simply obtaining oral consent.\n3.\n\nAdequate Details of Methods and Analysis for Replication a)\n\nThe explanation of the questionnaire administration process is lacking, as it does not clarify how discrepancies in the translated instrument were resolved beyond basic semantic adjustments. b)\n\nThe approach for calculating sample size lacks thorough justification for the selected parameters, including the 95% confidence interval and 80% power. c)\n\nWhile confirmatory factor analysis (CFA) is mentioned, there is insufficient detail on how the model's fit indices were computed and interpreted.\n3. Appropriateness of Statistical Analysis and Interpretation a)\n\nAlthough Cronbach’s alpha and CFA are utilized effectively, the write-up does not critically examine the potential limitations of these methods for cross-validating SEEQ in a different cultural and linguistic context. b)\n\nThere is no rationale provided for choosing AMOS v26, nor is there a discussion on its advantages over alternative software. c)\n\nWhile the discussion section highlights the findings positively, it fails to adequately consider the biases that may arise from the small sample size and the study's focus on a single institution.\n4. Availability of Source Data and Reproducibility a)\n\nThe write-up fails to specify how others can access the translated SEEQ questionnaire or the raw data, hindering transparency and reproducibility. b)\n\nWhile the process for securing permission from the tool’s developer is briefly mentioned, it lacks information on how the adapted Arabic version can be shared for future research. c)\n\nThere is no indication of whether the complete ethical approval document or informed consent template is available for review, which would enhance reproducibility.\n5. Suggestions about the general outlook of the paper/study: A)\n\nMore recent and regionally relevant studies should be incorporated to strengthen the introduction and discussion sections. B)\n\nA justification for methodological choices would benefit from a clearer focus on context-specific relevance and limitations. C)\n\nAdditionally, more detailed explanations regarding sample size calculation, ethical considerations, and translation processes are warranted. D)\n\nA critical assessment of the limitations of the statistical tools used and the contextual nuances in their interpretation would be beneficial. E)\n\nEnhancing transparency by specifying where supplementary materials (e.g., the dataset, translated questionnaire) can be accessed is also recommended.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1329
|
https://f1000research.com/articles/12-1517/v1
|
27 Nov 23
|
{
"type": "Systematic Review",
"title": "Physical activity in the treatment-resistance depression and non-remitted depression: a systematic review of randomized controlled trials",
"authors": [
"José Etxaniz-Oses",
"Nagore Iriarte-Yoller",
"Mikel Tous-Espelosin",
"Sara Maldonado-Martin",
"José Etxaniz-Oses",
"Nagore Iriarte-Yoller",
"Mikel Tous-Espelosin"
],
"abstract": "Background The objective of this systematic review was to analyze the effects of the physical activity (PA) intervention as an adjuvant strategy to pharmacological treatment in people with treatment-resistant depression (TRD) and non-remitted depression (NRD).\n\nMethods A search strategy was realized from five databases: PubMed, Cochrane Central Register of Controlled Trials, Scopus, SPORTDiscus, and Web of Science. Eleven articles attained the inclusion criteria. The Physiotherapy Evidence Database and Oxford’s Evidence Levels were used to classify the quality appraisal.\n\nResults The more significant outcome for this analysis was the improvement of depression by PA or exercise in TRD and NRD. According to the FITT (Frequency, Intensity, Time, and Type) principle, there was some variability in the PA intervention, and except for one article, they all were classified as excellent in terms of quality description.\n\nConclusions This review highlights the potential of PA intervention as an adjuvant program to improve different traits of TRD and NRD. The remission of depression seems to be higher after PA intervention, showing improvements in quality of life, sleep quality, executive function, and vitality.",
"keywords": [
"Major depression",
"Exercise",
"Mental Disorder",
"Physical Activity",
"Remission"
],
"content": "Introduction\n\nMajor depressive disorder (MDD) is one of the most prevalent mental illnesses in the world, as well as one of the most disabling (Gutiérrez-Rojas et al., 2020). Considered a multifactorial disease, MDD has a difficult physiopathology (Cichon et al., 2009). Besides antidepressant symptoms, the population with MDD presents toxic habits, such as smoking, alcohol intake, sedentarism, and/or physical inactivity, which leads to the appearance of different diseases (i.e., ictus, diabetes, cephalea, obesity, or coronary heart disease) (Gutiérrez-Rojas et al., 2020). Adding to that, around 60% of people with MDD have a moderate remission; the remainder accomplish the treatment-resistance depression (TRD) or non-remitted depression (NRD) criteria (Nemeroff, 2007). Although the definitions of TRD and NRD are not clear, in the two cases, the person who receives the treatment does not have a remission, with a poor or unsatisfactory response to at least two adequate (i.e., optimal dosage and duration) different classes of antidepressants. However, previous research studies have demonstrated a lack of consensus criteria in defining TRD (Harbi, 2012). On the other hand, NRD refers to patients’ reported partial response as defined by a screening Hamilton Depression Rating Scale (HDRS) score of ≥ 14 (Trivedi et al., 2006). The treatment for NRD and TRD consists of first and second-generation antidepressants acting over cerebral synapsis, so there is increased bioavailability of amines (serotonin, noradrenaline, and dopamine) (Cichon et al., 2009). Therefore, in this group of patients, a combination of different pharmacological therapy with antidepressant variety is not sufficient, and they could also need coadjuvant strategies such as physical activity (PA). However, discrepancies have been shown in this sense, with some studies showing no evidence in favor of exercise for patients with MDD (Krogh et al., 2017), but in others, exercise was associated with a moderate improvement effect over depressive symptoms in people with TRD and NRD (Carta et al., 2008; Harbi, 2012; Krogh et al., 2017; Mather et al., 2002; Mota-Pereira et al., 2011)\n\nFurther, in the latest PA guidelines by the World Health Organization, 150-300 minutes of moderate and/or 75-150 minutes of high-intensity aerobic PA, in conjunction with two days of resistance training recommendations, have been included for people with mental disorders (Bull et al., 2020).\n\nTherefore, taking into account the recommendations above, the controversial outcomes, and the different exercise protocols related to the FITT principle (i.e., frequency, intensity, time, and type of exercise) in people with TRD and NRD, the purpose of this systematic review was to analyze the effects of PA intervention as an adjunct strategy to pharmacological treatment in people with TRD and NRD.\n\n\nMethods\n\nThe systematic review protocol has been recorded in the PROSPERO database (CRD42022298347). It follows the recommendations suggested by the Preferred Reporting Items for Systematic Review and Meta-analyses (Page et al., 2021) (see Extended data, (Etxaniz-Oses et al., 2023)).\n\nFor the assessment and selection of the scientific articles, the following PICOS (Participant, Intervention, Comparator, Outcome, Study design) question was utilized:\n\n(1) Population: TRD and NRD population over 18 years of age. Treatment-resistance depression refers to inadequate response to at least two antidepressants of adequate doses and duration (Harbi, 2012). Non-remitted depression refers to patients’ reported partial response as defined by a screening Hamilton Depression Rating Scale (HDRS) score of ≥ 14 (Trivedi et al., 2006). Studies including only men, only women, or both sexes were considered.\n\n(2) Intervention: any type of PA or exercise intervention.\n\n(3) Comparator: pre- vs. post-intervention.\n\n(4) Outcome: depressive symptoms.\n\n(5) Study design: randomized controlled trials (RCT) and randomized trials.\n\nTwo authors (S.M-M and J.E-O) were responsible for retrieving selected articles having in mind the following inclusion criteria: (a) Treatment-resistant or non-remitted depression, (b) physical activity or exercise, (c) clinical trials or experimental trials, (d) studies published in English, (e) scientific studies but not such as a book, magazines, online websites, reports, guidelines or recommendations or thesis. Scientific studies were excluded if they did not accomplish the eligibility PICOS questions. The following exclusion criteria were: (a) suffered depression and responded to treatment, (b) included PA interventions combined with other strategies, (c) the intervention was not adaptations of PA (d) had less than 18 of age, (e) there was not a comparison between pre-and post-intervention, and (f) it was not an RCT.\n\nA systematic literature search was conducted in January 2022 using the following online databases: PubMed, Cochrane Central Register of Controlled Trials, Scopus, SPORTDiscus, and Web of Science. The search was developed by synonyms of treatment resistant and physical activity or exercise and was performed by the followings search strategies: In PubMed (“major depression” OR “depression disorder” OR “depressive disorder” OR “treatment resistant depression” OR “non-remitted major depressive” OR “poorly responsive depressive” OR “treatment-resistant patients” OR “treatment-resistant major depressive”) AND (“physical activity” OR exercise); in Cochrane, Web of Science and SPORTDiscus (“major depression” or “depression disorder” or “depressive disorder” or “treatment resistant depression” or “nonremitted major depressive” or “poorly responsive depressive” or “treatment-resistant patients” or “treatment-resistant major depressive”) and (“physical activity” or exercise); and in Scopus “major depression” OR “depression disorder” OR “depressive disorder” OR “treatment resistant depression” OR “nonremitted major depressive” OR “poorly responsive depressive” OR “treatment-resistant patients” OR “treatment-resistant major depressive” AND ““physical activity” OR “exercise”””.\n\nAfter duplicates were removed, the articles were revised by two independent authors (S.M-M and J.E-O) according to the title and abstract by the search strategy. After independent evaluation, the chosen articles were read and assessed by eligibility criteria. In case of discrepancies, a consensus would be reached among the authors. The following revision of articles was carried out using Rayyan Intelligent Systematic Review Software: the software was developed specifically to expedite the initial screening of abstracts and titles using a semi-automation process. Likewise, in the publications appear details of the investigation to realize the screening by eligibility criteria.\n\nThe more significant outcome for this analysis was the improvement of depression by PA or exercise in TRD and NRD.\n\nFor assessing included scientific articles, the Physiotherapy Evidence Database (PEDro) scale (de Morton, 2009) and Oxford’s Evidence Levels were used (Howick et al., 2009). The PEDro scale rates RCT on a scale from 0 (low quality) to 11 (high quality) related to scientific rigor (de Morton, 2009). Each measure is rated “yes” or “no”. Given that the assessors are rarely blinded and that it is impossible to blind the participants and investigators in supervised PA interventions, the items related to blinding (5–7) were removed from the scale. For this reason, the maximum result on the modified PEDro 8-point scale was 7 (highest score), as the first item is not included in the total score. The qualitative ratings were adjusted to those used in previous exercise-related systematic reviews as follows: 6–7 = “excellent”; 5 = “good”; 4 = “moderate”; and 0–3 = “poor”. Oxford’s Evidence levels range from 1 to 5, with 1a being systematic reviews of high-quality RCT, 1b individual RCT with a narrow confidence interval, 2a systematic review of cohort studies, 2b individual cohort study, 3a systematic review of a case-control study, 3b individual case-control study, 4 case-series, and 5 being expert opinions (Howick et al., 2009). Two researchers (S.M-M and J.E-O) inspected the methodology of each study independently. Disagreements regarding the appraisal of methodological quality were resolved through discussion between the reviewers.\n\n\nResults\n\nThe database searches identified 8086 references (see Extended data, (Etxaniz-Oses et al., 2023)). 2838 from PubMed, 926 in Cochrane, 4232 in Web of Science, 0 in Scopus, and 90 in SPORTDiscus. After eliminating duplicates (n=4383) and those that were not clinical trials (n=866), 2837 clinical trials were analyzed. A total of 2820 articles were removed by title, abstract, study design, or type of intervention. Consequently, 17 articles were assessed for eligibility. Six of those investigations were excluded because of the study design and intervention type. Finally, 11 articles were included in the systematic review. These were published between 2002 and 2017, showing the importance of PA in TRD and NRD (Supplementary data). Physical activity as a predictor of various factors of mental illness as well as producing benefits in depression was the highlight of the articles (Carta et al., 2008; Greer et al., 2014, 2016; Mather et al., 2002; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi, Greer, Blair, Church, Carmody, Grannemann, Galper, Dunn, Earnest, Sunderajan, & Henley, 2011).\n\nThe suppmental data included the main characteristic of the accepted studies in this systematic review. First, it is important to highlight that eight of the 11 chosen articles were from the same research project in the TRD or NRD population (n=275). Therefore, no variability was seen in the population and study design (i.e., two groups comparing different volumes of exercise doses) (Carta et al., 2008; Greer et al., 2014, 2016; Mather et al., 2002; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b, 2016, 2017; Toups et al., 2011, 2017; Trivedi et al., 2011). Nevertheless, the other three articles were not in the same research project (Carta et al., 2008; Mather et al., 2002; Mota-Pereira et al., 2011). Concerning the type of PA assessed, while two articles conducted a novelty concurrent exercise intervention (i.e., including endurance and resistance training in the same session) (Carta et al., 2008; Mather et al., 2002), a traditional training approach was observed in the other articles’ intervention, such as only aerobic continuous exercise (treadmill or cycle-ergometer) (Carta et al., 2008; Greer et al., 2014, 2016; Mather et al., 2002; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi et al., 2011), or weight-bearing strengthening exercise (Mota-Pereira et al., 2011). None of the control groups performed any special exercise, but pharmacological treatment (Carta et al., 2008), or health-educational talks (Mather et al., 2002).\n\nIn terms of the weekly frequency and time (volume) of PA, variability was shown in the studied articles (see Extended data, (Etxaniz-Oses et al., 2023)). First, there was only one intervention of five days per week (Mota-Pereira et al., 2011), while the rest of the articles were performed two days per week. Second, the duration of the session ranges lasting from 45 to 60 minutes. In addition, the period of assessment to analyze the changes ranged from 10 (Mather et al., 2002) to 12 weeks (Greer et al., 2014, 2016; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi et al., 2011); but on the other hand, there was one article with a period of eight months of assessment (Carta et al., 2008), and only one study presented a follow-up assessment after 24 weeks (Mather et al., 2002). All the reviewed studies used moderate intensities for exercise and continuous endurance training controlled by a heart rate monitor (Carta et al., 2008; Greer et al., 2014, 2016; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017) and rate of perceived exertion (Mota-Pereira et al., 2011). However, in two studies the intensity was not mentioned (Carta et al., 2008; Mather et al., 2002), and another survey carried out endurance training on the treadmill with an absolute exercise intensity of 5 km/h (Mota-Pereira et al., 2011). In this sense, the rest of the articles performed two different exercise doses (i.e., low dose: 4 kcal/kg/week (KKW) equivalent to 75 min/week, and high dose: 16 KKW equivalent to 210 min/week (Greer et al., 2014, 2016; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi et al., 2011).\n\nOverall, after PA intervention, in all but one of the reviewed articles (Rethorst et al., 2016), depression symptoms and functioning parameters improved, both in the TRD and NRD. The Hamilton Rating Scale for Depression (HRSD), Inventory of Depressive Symptoms-Clinical rated (IDS-C), Clinical Global Impression (CGI), and Geriatric Depression Scale (GDS), were the most widely used scales for depression screening (Carta et al., 2008; Mather et al., 2002; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b). In addition, the quality of life assessed with different instruments such as SF-36 and The World Health Organization Quality of Life (WHOQOL) also improved significantly (Greer et al., 2016). Further, sleep quality (Rethorst et al., 2013a), pro-inflammatory levels (Rethorst et al., 2013b), and some biomarkers of depression (Toups et al., 2011) showed better values after PA intervention. In addition, executive function and working memory were improved depending on the exercise volume; but psychomotor speed, attention, visual memory, spatial planning, instrumental and expressive roll, and cognitive function improved irrespective of the type or dose of exercise undertaken by participants (Greer et al., 2014, 2016). The remission of the participants also improved and was achieved a response to antidepressants with the PA as an adjuvant program on the different traits of TRD and NRD. Thus, in one of the RCTs, it was shown that 29.5% of the participants achieved remission (Trivedi et al., 2011), and the remission was analyzed with different scales, such as HRSD, IDS-C, CGI, and GDS (Mather et al., 2002; Mota-Pereira et al., 2011).\n\nTable 1 summarizes the PEDro scale and Oxford’s Evidence levels for the included articles in this systematic review. All the articles, but one (Carta et al., 2008), were classified as excellent. Inadequate concealed allocation to groups and the lack of similarity in the comparison groups at baseline were the methodological limitation in the article considered a “good” quality description. All papers were RCT, and for this reason, Oxford’s Evidence levels were 1b. All studies performed a comparison of both intra-group (pre- and post-PA-intervention) and inter-group (exercise vs. control group) when it was presented. Further, inclusion and exclusion criteria were defined, and blinding eligibility was presented.\n\n\nDiscussion\n\nThe objective of this study was to investigate the effects of PA intervention in TRD and NRD, describing the different parameters such as psychological, physical, and mental function and quality of life (Carta et al., 2008; Greer et al., 2014, 2016; Mather et al., 2002; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi et al., 2011). Over review determined 11 articles and identified that 1) PA intervention as an adjuvant program could improve different traits of TRD and NRD, 2) the remission of depression seems to be higher after PA intervention, showing also improvements in quality of life, sleep quality, executive function, or vitality, and 3) according to the FITT (Frequency, Intensity, Time, and Type) principle, there was some variability in the PA intervention, and except for one article (Carta et al., 2008), they all were classified as excellent in terms of quality description.\n\nA recent meta-analysis has found an interesting association between PA and incident depression, even below the public health recommendations, with an additional benefit when minimum recommendations are met (Pearce et al., 2022). Thus, in the present systematic review, even though different types of intervention (i.e., concurrent or endurance training) were performed in the reviewed articles, the depression decreased via HRSD (Mather et al., 2002; Mota-Pereira et al., 2011), and the quality of life increased (Carta et al., 2008; Greer et al., 2016), irrespective of PA type. Concerning only resistance intervention in patients with depression, previous studies have compared aerobic vs. nonaerobic exercise training and observed that both groups reduced depression scores, but with no significant difference between groups (Doyne et al., 1987; Martinsen et al., 1989). Taking into account all the aforementioned, and the recent World Health Organization PA guidelines for people with chronic conditions (Bull et al., 2020), it might be a good idea to include both resistance and endurance training in the adjuvant PA programs for TRD and NRD population, as it might result in better outcomes as seen in other populations (Silva et al., 2015; Stanton & Reaburn, 2013). In this sense, the prefrontal cortex, anterior cingulate cortex, hippocampus, and corpus callosum emerge as possible neural markers that benefit from exercise in people with depression (Gujral et al., 2017). It is time to confirm that during exercise, skeletal muscle releases valuable molecules that activate signals from skeletal muscle to different tissues, including the brain, highlighting that inactivity and loss of muscle mass may render the brain vulnerable to neurological dysfunction and disease (Delezie & Handschin, 2018; Isaac et al., 2021). Regarding the frequency of weekly sessions, interventions ranged from two to five sessions, but the most frequently used was 2.6 sessions per week. This information was not observed in other systematic reviews, which noted that th three sessions had the highest frequency per week (Perraton et al., 2010; Stanton & Happell, 2013). Our results could be associated with TRD and NRD patients’ poorer physical condition and chronicity over time compared to those patients with a diagnosis of only depression. The duration of the interventions in the articles was between 10 and 12 weeks in almost all of them (Greer et al., 2014, 2016; Mather et al., 2002; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi et al., 2011). However, another article used a longer intervention with an eight-month intervention (Carta et al., 2008). Other research on patients with depression used interventions for more than eight weeks (Perraton et al., 2010). Yet, it may be that an intervention with a duration of 10-12 weeks would be sufficient to improve depression in TRD and NRD. Regarding the intensity of exercise, in the current study, all the reviewed articles performed moderate-intensity training interventions (Carta et al., 2008; Greer et al., 2014, 2016; Mather et al., 2002; Mota-Pereira et al., 2011; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi et al., 2011), with no studies including high-intensity training. Thus, recent investigations are promoting the relevance of exercise intensity and modality (i.e., high-intensity interval training) to induce a higher metabolic myokine effect on brain health (Calverley et al., 2020; Hashimoto et al., 2021).\n\nThree articles carried out a comparison between the control (no exercise intervention) and experimental group (Carta et al., 2008; Mather et al., 2002; Mota-Pereira et al., 2011); the rest of the articles used a comparison with different doses of exercise (Greer et al., 2014, 2016; Rethorst et al., 2013a, 2013b, 2016; Toups et al., 2011, 2017; Trivedi et al., 2011). In the articles that compared the control and experimental groups, the experimental groups observed better results than the control groups. In the same way, the groups that performed a high dose of exercise improved more than a low dose of exercise.\n\nThe present systematic review of RCTs analyzing the effects of PA intervention in patients with TRD and NRD determined the benefits of PA not only in the decrease of the depression symptoms but also in other variables related to the quality of life, such as sleep quality, executive and cognitive function, and memory. Therefore, regarding clinical practice and considering the results and the quality of the reviews, there is scientific evidence for a patient with TRD or NRD to recommend PA as an adjuvant treatment. However, there is a complex interplay in the type of exercise program or intervention intensity, hence, a need for further investigation.",
"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: Physical activity in the treatment-resistance depression and non-remitted depression: a systematic review of randomized controlled trials, https://doi.org/10.5281/zenodo.10044119 (Etxaniz-Oses et al., 2023).\n\nThis project contains the following extended data:\n\n- Extended data-supplementary data. Main characteristic of studies that analysed resistant treatment or non-remitted depression and physical activity\n\n- Flow diagram-supplementary data. Flowchart of the systematic review following the rules of PRISMA\n\nZenodo: PRISMA checklist for ‘Physical activity in the treatment-resistance depression and non-remitted depression: a systematic review of randomized controlled trials’, https://doi.org/10.5281/zenodo.10044119 (Etxaniz-Oses et al., 2023).\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\nde Morton NA : The PEDro scale is a valid measure of the methodological quality of clnical trials: a demographic study. Aust. J. Physiother. 2009; 55: 129–133. PubMed Abstract | Publisher Full Text\n\nBull FC, Al-Ansari SS, Biddle S, et al.: World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br. J. Sports Med. 2020; 54(24): 1451–1462. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCalverley TA, Ogoh S, Marley CJ, et al.: HIITing the brain with exercise: mechanisms, consequences and practical recommendations. Wiley; 2020. Publisher Full Text\n\nCarta MG, Hardoy MC, Pilu A, et al.: Clinical practice and epidemiology in mental health improving physical quality of life with group physical activity in the adjunctive treatment of major depressive disorder.2008. Publisher Full Text\n\nCichon S, Craddock N, Daly M, et al.: Genomewide association studies: history, rationale, and prospects for psychiatric disorders. Am. J. Psychiatry. 2009; 166(5): 540–556. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDelezie J, Handschin C: Endocrine Crosstalk Between Skeletal Muscle and the Brain. Front. Neurol. 2018; 9: 698. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDoyne EJ, Ossip-Klein DJ, Bowman ED, et al.: Running Versus Weight Lifting in the Treatment of Depression. J. Consult. Clin. Psychol. 1987; 55(5): 748–754. Publisher Full Text\n\nEtxaniz-Oses J, Iriarte-Yoller N, Tous-Espelosin M, et al.: Physical activity in the treatment-resistance depression and non-remitted depression: a systematic review of randomized controlled trials. Zenodo. 2023. Publisher Full Text\n\nGreer T, Grannemann B, Chansard M, et al.: Dose-dependent changes in cognitive function with exercise augmentation for major depression: Results from the TREAD study. Eur. Neuropsychopharmacol. 2014; 25(2): 248–256. PubMed Abstract | Publisher Full Text\n\nGreer T, Trombello J, Rethorst C, et al.: Improvements in pshychosocial functioning and health-related quality of life following exercise augmentaion in patients with treatment response but nonremitted major depressive disorder: results from the TREAD study. Depress. Anxiety. 2016; 33(9): 870–881. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGujral S, Aizenstein H, Reynolds CF, et al.: Exercise effects on depression: Possible neural mechanisms. Gen. Hosp. Psychiatry. 2017; 49: 2–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGutiérrez-Rojas L, Porras-Segovia A, Dunne H, et al.: Prevalence and correlates of major depressive disorder: a systematic review. Rev. Bras. Psiquiatr. 2020; 42(6): 657–672. Publisher Full Text\n\nHarbi KSA: Treatment-resistant depression: Therapeutic trends, challenges, and future directions. Patient Prefer. Adherence. 2012; 6: 369–388. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHashimoto T, Tsukamoto H, Ando S, et al.: Effect of Exercise on Brain Health: The Potential Role of Lactate as a Myokine. Metabolites. 2021; 11(12): 813. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHowick J, Chalmers I, Glasziou P, et al.: OCEBM Levels of Evidence — Centre for Evidence-Based Medicine (CEBM). University of Oxford; 2009. Retrieved Dec 12, 2021. Reference Source\n\nIsaac AR, Lima-Filho RAS, Lourenco MV: How does the skeletal muscle communicate with the brain in health and disease? Neuropharmacology. 2021; 197: 108744. PubMed Abstract | Publisher Full Text\n\nKrogh J, Hjorthøj C, Speyer H, et al.: Exercise for patients with major depression: a systematic review with meta-analysis and trial sequential analysis. BMJ Open. 2017; 7(9): e014820. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartinsen EW, Hoffart A, Solberg O: Comparing aerobic with nonaerobic forms of exercise in the treatment of clinical depression: A randomized trial. Compr. Psychiatry. 1989; 30(4): 324–331. PubMed Abstract | Publisher Full Text\n\nMather A, Rodriguez C, Guthrie M, et al.: Effects of exercise on depressive symptoms in older adults with poorly responsive depressive disorder. Br. J. Psychiatry. 2002; 180(411-145): 411–415. PubMed Abstract | Publisher Full Text\n\nMota-Pereira J, Silverio J, Carvalho S, et al.: Moderate exercise improves depression parameters in treatment-resistant patients with major depressive disorder. J. Psychiatr. Res. 2011; 45(8): 1005–1011. PubMed Abstract | Publisher Full Text\n\nNemeroff CB: Prevalence management treatment resistant depression. J. Clin. Psychiatry. 2007; 68(8): 17–25. PubMed Abstract\n\nPage MJ, Mckenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021; 372. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPearce M, Garcia L, Abbas A, et al.: Association Between Physical Activity and Risk of Depression. American Medical Association (AMA); 2022; vol. 79. : pp. 550–559. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPerraton LG, Kumar S, Machotka Z: Exercise parameters in the treatment of clinical depression: a systematic review of randomized controlled trials. J. Eval. Clin. Pract. 2010; 16(3): 597–604. PubMed Abstract | Publisher Full Text\n\nRethorst C, South C, Rush AJ, et al.: Prediction of treatment outcomes to exercise in patients with nonremitted major depressive disorder. Depress. Anxiety. 2017; 34(12): 1116–1122. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRethorst C, Sunderajan P, Greer T, et al.: Does exercise improve self-reported sleep quality in non-remitted major depressive disorder? Psychol. Med. 2013a; 43(4): 699–709. PubMed Abstract | Publisher Full Text\n\nRethorst C, Toups M, Greer T, et al.: Pro-inflammatory cytokines as predictors of antidepressant effects of exercise in major depressive disorder. Mol. Psychiatry. 2013b; 18(10): 1119–1124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRethorst C, Tu J, Carmody T, et al.: Atypical depressive symptoms as a predictor of treatment response to exercise in Major Depressive Disorder. J. Affect. Disord. 2016; 200: 156–158. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSilva BAE, Cassilhas RC, Attux C, et al.: A 20-week program of resistance or concurrent exercise improves symptoms of schizophrenia: results of a blind, randomized controlled trial. Braz. J. Psychiatry. 2015; 37(4): 271–279. Publisher Full Text\n\nStanton R, Happell B: Exercise for mental illness: A systematic review of inpatient studies. Wiley; 2013. Publisher Full Text\n\nStanton R, Reaburn P: Exercise and the treatment of depression: A review of the exercise program variables. J. Sci. Med. Sport. 2013; 17(2): 177–182. Publisher Full Text\n\nToups M, Carmody T, Greer T, et al.: Exercise is an Effective Treatment for Positive Valence Symptoms in Major Depression. J. Affect. Disord. 2017; 209: 188–194. PubMed Abstract | Publisher Full Text | Free Full Text\n\nToups M, Greer T, Kurian B, et al.: Effects of serum Brain Derived Neurotrophic Factor on exercise augmentation treatment of depression. J. Psychiatr. Res. 2011; 45(10): 1301–1306. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTrivedi M, Greed T, Grannemann B, et al.: TREAD: TReatment with Exercise Augmentation for Depression: study rationale and design. CA DESIGN Clinical Trials. 2006; 3: 291–305. PubMed Abstract | Publisher Full Text\n\nTrivedi M, Greer TL, Blair SN, et al.: Exercise as an augmentation treatment for nonremitted major depressive disorder: a randomized, parallel dose comparison. J. Clin. Psychiatry. 2011; 72(5): 677–684. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "278378",
"date": "03 Jun 2024",
"name": "Petros C Dinas",
"expertise": [
"Reviewer Expertise Systematic review and meta-analysis in biological studies"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\n1. The sections of \"Eligibility Criteria\" and \"Identification and selection of studies\" should be merged with the PICOS approach, or a section of the selection method should be created. As it is stated now both sections contain eligibility criteria. 2. It's been more than two years from the searching date. This requires an update. A searching on PubMed on the 3rd June 2024 yield 3188 publications, indicating that potential eligible papers may have been published the last 2 years. 3. It is not clear whether the screening of the eligible publications was also based on abstract and full texts reading. 4. In PRISMA flowchart, it is reported that studies that were not clinical trials were excluded. However, in the eligibility criteria is reported that experimental studies is an accepted type of publications. Please define if only clinical trials were included in the systematic review. 5. For clarity, I suggest the results section to include sub-sections for searching, selection, and risk of bias results, main outcomes as well as main characteristics of the included studies. 6. The Reviewer performed a searching in Scopus on the 3rd June 2024, using the given algorithm. This search yield 72153 publications. However, in the results section is reported that Scopus yield 0 results during the search. Please check if the searching in Scopus is correct. 7. It is confusing what was the \"comparator\" in the included studies. The eligibility criteria are not clear in terms of this, which consequently provides an unclear view of the results in relation to the research question. In other words the conclusion of the study is based on mixed data of comparison between exercisers and non exercisers and between exercisers and exercisers as controls. 8. Based on the main results provided in the supplement, the authors should consider a meta-analysis. If not, a justification of not using a meta-analysis should be given and the type of data synthesis should be reported. 9. The Discussion does not provide any limitations of the systematic review\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": [
{
"c_id": "11712",
"date": "19 Jun 2024",
"name": "SARA MALDONADO-MARTIN",
"role": "Author Response",
"response": "Thank you so much for your comments. Hopefully we will have the opportunity to answer you to improve the paper."
},
{
"c_id": "11835",
"date": "23 Jul 2024",
"name": "SARA MALDONADO-MARTIN",
"role": "Author Response",
"response": "SYSTEMATIC REVIEW Physical activity in the treatment-resistance depression and non-remitted depression: a systematic review of randomized controlled trials We greatly appreciate the reviewer's time and insight. Your comments and our subsequent revision have improved our manuscript. We have reviewed the entire manuscript and made changes to improve it. Reviewer comment: The \"Eligibility Criteria\" and \"Identification and selection of studies\" sections should be merged with the PICOS approach, or a section of the selection method should be created. As it is stated now, both sections contain eligibility criteria. Author response: Amended, we have reorganized this section. Reviewer comment: It's been more than two years since the search date. This requires an update. A search on PubMed on the 3rd of June 2024 yielded 3188 publications, indicating that potentially eligible papers may have been published in the last 2 years. Author response: Dear reviewer. Thanks for your message. This paper was submitted one year ago (2023), and your review was performed just a few weeks ago. This point justifies the date of our search data. Agree with you we have conducted a new search data with the same search strategy and the data have been updated. Reviewer comment: It is not clear whether the screening of the eligible publications was also based on abstract and full-text reading. Author response: Amended. We have better explained this point in the Data Screening and Extraction. Reviewer comment: In PRISMA flowchart, it is reported that studies that were not clinical trials were excluded. However, in the eligibility criteria, it is reported that experimental studies is an accepted type of publications. Please define if only clinical trials were included in the systematic review. Author response: Many thanks for your comment. We have corrected the PRISMA flowchart. Reviewer comment: For clarity, I suggest the results section to include sub-sections for searching, selection, and risk of bias results, main outcomes as well as main characteristics of the included studies. Author response: Many thanks. Now is everything more straightforward. Reviewer comment: The Reviewer performed a searching in Scopus on the 3rd June 2024, using the given algorithm. This search yield 72153 publications. However, in the results section is reported that Scopus yield 0 results during the search. Please check if the searching in Scopus is correct. Author response: Dear reviewer, you can find below an image of the research. 567 document were found with SCOPUS data base. We have changed the search or Scopus to better adjust it: \"major depression\" OR \"depression disorder\" OR \"depressive disorder\" OR \"treatment resistant depression\" OR \"nonremitted major depressive\" OR \"poorly responsive depressive\" OR \"treatment-resistant patients\" OR \"treatment-resistant major depressive\" AND \" physical AND activity \" OR \" exercise \". Reviewer comment: It is confusing what was the \"comparator\" in the included studies. The eligibility criteria are not clear in terms of this, which consequently provides an unclear view of the results in relation to the research question. In other words the conclusion of the study is based on mixed data of comparison between exercisers and non exercisers and between exercisers and exercisers as controls. Author response: Thank you for your comment. You are right. We compare intra groups and inter groups. In this sense, we have add more information. Comparator: intra-group (pre- vs. post-intervention) and inter-group (control vs. exercise intervention). Reviewer comment: Based on the main results provided in the supplement, the authors should consider a meta-analysis. If not, a justification of not using a meta-analysis should be given and the type of data synthesis should be reported. Author response: Thank you for your comment. In the methods have added a paragraph related to that. Although we understand that the meta-analysis of the results of the different studies may provide objective global information on certain variables, the present study aims not to perform a meta-analysis but to provide a global view of the scientific evidence presented in the literature. Doing it this way allows us to give a more global vision and include those variables related to \"what interests us\" that cannot be meta-analyzed due to the lack of sufficient cohorts. On the other hand, for quantitative meta-analysis, tables reporting results should include all important information and test statistics, including mean effect sizes, standard error, and confidence intervals. Further, the methods for analyzing the primary outcomes should be the same in all studies to compare results. Reviewer comment: The Discussion does not provide any limitations of the systematic review. Author response: Amended. Limitations have been added."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1517
|
https://f1000research.com/articles/13-892/v1
|
06 Aug 24
|
{
"type": "Clinical Practice Article",
"title": "A Revolutionary Device for Endovascular Aortic Repair of Abdominal Aortic Aneurysm: A Pilot Study",
"authors": [
"Taofan Taofan",
"Iwan Dakota",
"Sung Gwon Kang",
"Suko Adiarto",
"Suci Indriani",
"Ruth Grace Aurora",
"Rendra Mahardika Putra",
"Bagas Adhimurda Marsudi",
"Melani Limenco Benly",
"Macmilliac Lam",
"Muhammad Rafli Iqbal",
"Bagus Herlambang",
"Yoga Yuniadi",
"Renan Sukmawan",
"Bambang Widyantoro",
"Iwan Dakota",
"Sung Gwon Kang",
"Suko Adiarto",
"Suci Indriani",
"Ruth Grace Aurora",
"Rendra Mahardika Putra",
"Bagas Adhimurda Marsudi",
"Melani Limenco Benly",
"Macmilliac Lam",
"Muhammad Rafli Iqbal",
"Bagus Herlambang",
"Yoga Yuniadi",
"Renan Sukmawan",
"Bambang Widyantoro"
],
"abstract": "Background Endovascular repair for abdominal aortic aneurysms (AAA) has been the gold standard since it was established in 1991. Various graft configurations have been developed to overcome the limitations of endovascular aortic repair (EVAR), including contralateral gate cannulation (CGC). We propose a new device and technique intended to simplify endovascular AAA repair, along with reports of its application in six patients.\n\nIntervention The Taofan and Kang (T&K) bidirectional endovascular aortic repair (B-EVAR (B-EVAR) device uses a main-body stent graft, two-limb extensions, and bare metal stent. The procedure involved accessing the right and left femoral arteries, followed by standard aortography evaluation using a pigtail catheter through the contralateral femoral access. The main body stent graft is deployed through ipsilateral femoral access using a balloon catheter, while the contralateral gate is cannulated with a hydrophilic coated wire. Both balloons were inflated simultaneously to ensure that the wires were in different lumens. Contralateral and ipsilateral extensions were deployed using a limb extension stent graft. Standard aortography evaluation was repeated.\n\nResult T&K B-EVAR pilot procedures proved successful in various cases, from simple to complex anatomy, and even with varied graft stent deployment strategies. None of the patients had complications or prolonged length of stay (LOS). Follow-up CT did not reveal any high-pressure endoleaks.\n\nConclusion T&K B-EVAR has been proven to simplify endovascular AAA repair in six patients with excellent results. It is also reproducible, potentially universally applicable, and can offer operators ease of use, faster procedure times, reduced fluoroscopy times, and reduced contrast usage.",
"keywords": [
"Endovascular Aortic Repair",
"Abdominal Aortic Aneurysm",
"Stent Graft",
"B-EVAR",
"Contralateral Gate Cannulation"
],
"content": "Introduction\n\nAbdominal Aortic Aneurysm (AAA) is defined as a dilation equal to or greater than 3 cm in size or an increase of ≥1.5 times the normal diameter at the renal artery level.1,2 Its prevalence increases with age. The current global prevalence of AAA in patients aged 60 years or older is estimated to be around 1.2-3.3%.2 While in the Asian population, the overall prevalence was around 2.56% in patients with cardiovascular risk factors.3 In 2017, it was reported that AAA caused 167,000 deaths and 3 million disability-adjusted life years worldwide.4\n\nIntervention is recommended for AAA patients with rapid aneurysm growth (>5 mm/6 months) or a fusiform aneurysm with a maximum diameter of 5.5 cm or more. Studies have shown that endovascular aortic repair (EVAR) provides better results than open repair in terms of perioperative mortality rate, 30-day mortality rate, procedure time, blood loss, and length of stay (LOS).5 EVAR procedures require experienced operators in well-equipped centers with proper devices and operating rooms. They are expected to have sufficient training to perform catheter-based interventions with the recommended minimum number of endovascular procedures, including 80 endovascular therapeutic procedures, 100 endovascular diagnostic procedures, and 20 EVARs.6,7 Furthermore, EVAR has been shown to use considerable contrast when performed.8 Thus, various graft configurations have been developed over time to subjugate the limitations that come with EVAR, including one of the most challenging and time-consuming parts of EVAR, which is the contralateral gate cannulation (CGC).9 We propose a new device and technique intended to simplify endovascular AAA repair alongside reports of its application on six patients.\n\n\nMethod\n\nThe procedures were performed at the National Cardiovascular Center in Harapan Kita, Jakarta, Indonesia, which saw approximately 55 EVAR and thoracic endovascular aortic repair (TEVAR) cases per year. A vascular intervention consultant cardiologist with more than ten years of experience performed the procedures, assisted by a fellow vascular intervention student.\n\nPrior to conducting this study, we sought ethical approval from the National Cardiovascular Center in Harapan Kita. The stages involved in obtaining ethical approval included submitting the research proposal, developing the initial study protocol, creating a prototype, conducting stent graft trials, and ultimately presenting at a full board meeting. We received ethical clearance from the National Cardiovascular Center in Harapan Kita under the reference number DP.04.03/KEP161/EC086/2023 on September 12, 2023. The ethics committee authorized the study, ensuring that the research subjects’ rights are protected and confirming that the research adheres to the ethical, legal, social, and non-clinical standards outlined in the Nuremberg Code and the Helsinki Declaration.\n\nTaofan & Kang bidirectional endovascular aortic repair (T&K B-EVAR) is a newly developed universal device intended to convert the bifurcated EVAR technique to a tubular/trunk-type EVAR with limb extensions deployed according to Taofan-Kang Modified Mitsudo’s Kissing Balloon Formula. The device consists of a main body stent graft with a bare stent and encapsulated two-limb extensions (Figure 1A-B).\n\n(A) Primary body stent graft from the front, side, and back. (B) Limb extensions from the front and side. (C) Axial view of the device.\n\nThe standard procedure requires two access sites from the bilateral common femoral arteries, which are achieved by surgical cutdown. Standard aortography was performed using a 5 Fr marker pigtail catheter through the contralateral femoral artery. The guidewires were placed in the ascending aorta. Both wires were replaced with an extra stiff wire. Subsequently, both contralateral and ipsilateral femoral artery sheaths are exchanged with larger sheath sizes ranging from 16 F to 18 F SEAL NOVUS Body Stent Graft™ (S&G Biotech, Yongin, Korea) deployment is performed through the more patent, more anatomically ideal access site. A balloon catheter is placed on the ipsilateral side. At the same time, the contralateral gate was cannulated using a 0.035 hydrophilic coated wire with the assistance of a multipurpose catheter, and another balloon catheter was placed. Both balloons were inflated simultaneously to ensure that they were in different lumens. If both balloons are successfully inflated, it can be inferred that both wires successfully cannulated the separate lumens. The contralateral and ipsilateral limb extensions were deployed using a SEAL NOVUS Limb stent graft™ (S&G Biotech, Yongin, Korea). The standard aortography evaluation procedure was performed to evaluate the graft stent position, apposition, endoleaks, and patency of the renal arteries. Many follow the same procedure in the six cases presented. However, certain cases have highlighted the applicability of T&K B-EVAR, even with challenging anatomical morphology.\n\n\nCase presentation\n\nAn 83-year-old man was admitted with sharp, pulsing abdominal pain 1 year prior to presentation. The patient also had a history of hypertension. Laboratory results showed normal hemoglobin counts (Hb 12.2 mg/dL) and mildly reduced eGFR (Ureum 35.6 mg/dL, Creatinine 1.33 mg/dL, and eGFR 53 ml/min/1.73 m2). A CT-Scan angiography (CTA) was performed. It revealed an AAA from the infrarenal region to the aortic bifurcation 79 mm in length and a maximum sac diameter of 58.2 mm, and dilatation of the right common iliac artery with a diameter of 21.1 mm (Figure 2A). A T&K B-EVAR procedure was then performed for the patient.\n\n(A) CT of the 1st patient’s aortic pathology. (B) Diagnostic angiography. (C-H) T&K B-EVAR step-by-step with limb extension deployment using a ballerina technique. (I) Post-procedure follow-up CT.\n\nSurgical cutdown was performed to gain access to the right and left femoral arteries. Initial aortography revealed an infrarenal fusiform abdominal aorta aneurysm (Figure 1B). A SEAL NOVUS Body Stent Graft 26(20) × 90 mm × 15 × 550 (S&G Biotech, Yongin, Korea) was deployed through the right femoral artery. Subsequent wiring was performed using a 0.035 hydrophilic coated wire, guided by an MP2/5F catheter. Deployment of the SEAL NOVUS Body Stent Graft 2210 × 120 mm 18 × 550 mm (S&G Biotech, Yongin, Korea) was performed through ipsilateral access (Figure 2C-G). Aortography showed the stent in a good position, a type 1 B endoleak, and stenosis in the intrastent abdominal aorta. Contralateral and ipsilateral limb extensions using the SEAL NOVUS Limb Stent Graft 12 (24) × 80 mm 15 × 550 mm (S&G Biotech, Yongin, Korea) were deployed (Figure 2H). When withdrawing the olive tip through ipsilateral femoral access, it was difficult to retract the apparatus. Hence, we continued to snare from the brachial access site, which allowed us to free the apparatus. Aortography revealed a minimal endoleak from the right iliac artery and intrastent stenosis at the abdominal aorta. Post-dilatation of the contralateral iliac stent was performed using a balloon catheter 10-46 mm inflated to 9 cc. Contralateral and ipsilateral intrastent post-dilatation were performed simultaneously using peripheral 10 × 60 mm and 10 × 60 mm balloons, respectively. Final angiography showed good stent position and no residual endoleaks or intrastent stenosis (Figure 2H). The total contrast was 130 mL hexiol, and the dose area product (DAP) was 205.48 Gy.cm2. The total procedure time was 1 h and 50 min, and the fluoroscopy times were 41 min and 56 s, respectively.\n\nThe patient was discharged without any complaints after four days. Follow-up CTA performed 3 days and 2 months after the procedure showed a deployed stent in the infrarenal aorta until the left and right common iliac arteries without endoleaks (Figure 2I).\n\nA surgical cutdown was performed to gain access to the right and left femoral arteries, a puncture of both arteries was subsequently performed, and 8F sheaths were inserted. Wiring via left femoral artery access was performed using an exchange wire 0.035” 260 mm, placed in the abdominal aorta, and then exchanged with a marker 5F Pigtail catheter. Wiring through the contralateral access site using an extra stiff wire was performed and placed in the abdominal aorta. Initial aortography revealed an infrarenal fusiform AAA. The contralateral femoral access sheath was exchanged between 8F and 16F. SEAL NOVUS Body Stent Graft 32(26) × 90 mm 18 × 550 mm (S&G Biotech, Yongin, Korea) was deployed through contralateral femoral access (Figure 3B-C). Balloon dilation was performed using a peripheral balloon catheter (10 mm × 80 mm) through the right access, placed inside the right side of the proximal main body, and inflated to 4 atm. Simultaneous cannulation of the main body was performed using a 0.035 hydrophilic coated wire, guided by an MP2/5F catheter (Figure 3D-E). Once subsequent wiring of the ipsilateral and contralateral lumens was ensured, limb extensions were deployed using the SEAL NOVUS Limb Stent Graft 12 (24) × 100 mm 15 × 550 mm (S&G Biotech, Yongin, Korea) and SEAL NOVUS Limb Stent Graft 12 × 120 mm 15 × 550 mm (S&G Biotech, Yongin, Korea), respectively. Stenosis of the left iliac artery was found during angiography (Figure 3F), and balloon dilatation was performed to resolve this issue (Figure 3G-I). Evaluation aortography showed that the stent was in a good position, with no visible endoleak or patent renal arteries (Figure 3J). Iopamiro 370 contrast medium was used, totaling 70 mL, and the dose area product (DAP) was 201.02 Gy.cm2. The total procedure time was 1 h and 10 min, and the fluoroscopy times were 33 min and 37 s, respectively.\n\n(A) Pre-procedure CT of the 2nd patient’s aortic pathology. (B-E) Deployment of T&K B-EVAR. (F-J) Stenosis of the left iliac artery and subsequent ballooning with good results. (K) Post-procedure CT scan evaluation.\n\nAfter five days, the patient was discharged without any complaints. Follow-up CTA within the same month showed good graft position and no endoleak (Figure 3K).\n\nA 67-year-old male was initially suspected of having an abdominal aortic aneurysm due to recurrent abdominal pain. Ultrasonography revealed an abdominal mass. The patient had a history of hypertension, diabetes, and dyslipidemia. Laboratory results showed normal hemoglobin (14.3 Â g/dL) and mildly reduced eGFR (Ureum 37.3 mg/dL, Creatinine 1.19 mg/dL, eGFR 67 ml/min/1.73 m2). CT-scan Angiography (CTA) revealed a challenging infrarenal AAA anatomy with a very short neck (9 mm), a maximum aneurysm diameter of 70.6 mm, and a length of 127 mm (Figure 4A).\n\n(A) Pre-procedure CT scan of the 3rd patient’s aortic pathology. (B) Diagnostic angiography. (C-D) Standard deployment of T&K B-EVAR with angiography evaluation. (E-F) Coiling of right internal iliac artery and coronary angiography evaluation. (G-H) The deployment of limb extensions and evaluation showed slow flow through the graph stent. (I-J) Balloon dilatation intrastent. (K) Evaluation angiography without endoleaks. (L) Post-procedure CT scan evaluation.\n\nThe Standard T&K B-EVAR procedure was performed in this patient, and surgical cutdown was performed for access to the right and left femoral arteries. Aortography confirmed several challenging anatomical features on the CT scan: a very short neck, neck angulation, and right common iliac aneurysm extending to the right internal iliac artery (Figure 4B-D). After the main body was deployed, a JR 3.5/6F catheter was introduced via ipsilateral femoral access and crossed over into the right internal iliac artery. To occlude the vessel, several coils were used: 6 × 6.5 mm (2 coils), 5 × 5.5 mm (2 coils), and 4 × 3.7 (1 coil) (Figure 4E-F). Standard cannulation of both lumens was successful and both balloons were successfully inflated. However, the balloon in the contralateral limb could not be inflated maximally because of wire twisting. An additional bail-out strategy was performed using antegrade wiring and guidewire via contralateral brachial access. The peripheral balloon was inflated to 4 atm in the ipsilateral limb. At the same time, the wire was advanced into the contralateral limb and externalized towards the ipsilateral femoral artery access (Figure 4G-H). Simultaneous ballooning of both ipsilateral and contralateral limbs was successful, and twisting of the wire was not observed, as confirmed by the LAO, AP, and RAO views (Figure 4I-J). Finally, limb graft extension using SEAL Novus Flared™ 12 (14) × 100 mm, 15 × 550 mm (S&G Biotech, Yongin, Korea) was deployed from the abdominal aorta with the distal portion right above the left internal iliac artery. The final aortography evaluation showed a good stent position and minimal type 1 B endoleak. After additional ballooning, final aortography showed no endoleaks (Figure 4K). The total contrast used was 230 cc, DAP 95350.47 mikroGy.m2, and fluoroscopy time was 1 h and 23 min. CT scan tomography revealed promising results, good graft stent position, and no endoleaks.\n\nThe patient was discharged without any complaints after five days. Follow-up CTA 3 months after the procedure showed an excellent stent position at the infrarenal aorta until the left and right common iliac arteries without endoleaks (Figure 4L).\n\nA 71-year-old man was admitted for EVAR due to a pulsing sensation in the stomach. The patient had a history of undergoing a CABG procedure approximately 11 years ago and had a history of hypertension. Laboratory results revealed a normal hemoglobin level (13.6 g/dL) and slightly decreased eGFR (Ureum 38.7 mg/dL, Creatinine 1.41 mg/dL, and eGFR 53 ml/min/1.73 m2). CT-Scan Angiography (CTA) was performed. It showed an AAA with thrombus from the infrarenal region after the bilateral renal arteries to the aortic bifurcation around 103.55 mm in length with a maximum sac diameter of 40.9 mm, and right common iliac artery aneurysm with thrombus, as well as intermittent subtotal thrombus with irregularity in the bilateral internal iliac artery (Figure 5A-C). The T&K B-EVAR procedure was performed.\n\n(A) Pre-procedural CT scan. (B) Axial CTA. (C) Sagittal CTA. (D-I) T&K B-EVAR step-by-step. (J) Post-procedure aortography with good stent apposition and no endoleaks. (K) Post-procedural CT scan evaluation had good results with no signs of endoleaks.\n\nSurgical cutdown was performed to gain access to the right and left femoral arteries. Initial aortography revealed an infrarenal fusiform abdominal aortic aneurysm (Figure 5D-E). A SEAL NOVUS Body stent graft (24 × 90 mm 18 × 550 mm (S&G Biotech, Yongin, Korea) was deployed through contralateral femoral access (Figure 5F). After successful wiring, the SEAL NOVUS Limb Stent Graft 12 (16) × 80 mm 15 × 550 mm (S&G Biotech, Yongin, Korea) was deployed through contralateral femoral access. The SEAL NOVUS Limb Stent Graft 12 × 100 mm 15 × 550 mm (S&G Biotech, Yongin, Korea) was deployed through ipsilateral femoral access (Figure 5G-I). Aortography evaluation showed the stent in a good position and no endoleaks (Figure 5J). The total contrast was 90 mL Ultravist370, and the dose area product (DAP) was 51.722 Gy.cm2. The fluoroscopy times were 17 min and 9 s, respectively.\n\nAfter four days, the patient was discharged without any complaints. A follow-up CTA 1 month after the procedure revealed promising results: a well-expanded and apposed graft stent without an endoleak (Figure 5K).\n\nA 67-year-old man was admitted to our hospital with AAA and a history of hypertension and dyslipidemia. Laboratory results showed normal hemoglobin level (15.3 g/dL) and signs of renal insufficiency (Ureum 56.2 mg/dL, Creatinine 1.85 mg/dL, and eGFR 40 ml/min/1.73 m2). A CT-Scan angiography (CTA) revealed a challenging AAA morphology with a conical-shaped neck, thrombus throughout the whole aneurysm from the infrarenal region to the aortic bifurcation around 113.7 mm in length, a maximum sac diameter of 58 mm, a very short common iliac artery (15.4 mm), and a small access diameter (Figure 6A).\n\n(A) Pre-procedure CT scan. (B-C) Procedural diagnostic angiography. (D-E) Deployment of main body stent. (F) Angiographic evaluation revealing the expansion of graft stent. (G-H) deployment and ballooning of extensions. (I) Angiographic evaluation with reduced flow through the left extension limb. (J) Ballooning of limb extension. (K) After the angiography evaluation after additional limb extension deployment, the results showed good flow and no endoleak. (L) Post-procedure CTA was showing promising results.\n\nSurgical cutdown was performed to gain access to the right and left femoral arteries. A double puncture was performed in the right and left femoral arteries. Initial aortography showed an infrarenal fusiform abdominal aortic aneurysm (Figure 6B-C). For this patient, a sheathless approach was used because of the relatively small size of the right iliac artery. A SEAL NOVUS Body Stent Graft 24 × 90 mm 18 × 550 mm (S&G Biotech, Yongin, Korea) was deployed, and subsequently, both limb extension grafts were deployed (Figure 6D-E). Aortography evaluation showed under-expansion of the contralateral limb extension, particularly near the left common iliac artery, suspected to be due to arterial stenosis (Figure 6F). Balloon inflation was performed using a 10 mm × 40 mm peripheral balloon catheter, inflated several times up to a maximum pressure of 6 atm, at the main graft stent up to the left common iliac artery (Figure 6G-J). Aortography revealed that the stent coverage was insufficient; hence, another 12 × 40 mm 8 × 900 mm (S&G Biotech, Yongin, Korea) was deployed through the left femoral artery. Final aortography revealed good stent position, no endoleak, and good flow in the left iliac artery (Figure 6K). Ultravist 370 contrast was used at approximately 90 mL, and the dose area product (DAP) was approximately 92.4 Gy.cm2. The total procedure time was 1 h and 32 min, and the fluoroscopy times were 34 min and 9 s, respectively.\n\nThe patient was discharged without any complaints after six days. A follow-up CTA 4 months after the procedure revealed promising results, a well-expanded and apposed graft stent without any endoleak (Figure 6L).\n\nA 76-year-old man was admitted with a burning sensation in the chest and epigastric areas. He was suspected to have AAA and had a history of hypertension. Laboratory results showed a normal hemoglobin level (13.4 g/dL) and signs of chronic kidney disease (Ureum 26.1 mg/dL, Creatinine 1.83 mg/dL, and eGFR 38 ml/min/1.73 m2). CT-Scan Angiography (CTA) was then performed, and it showed an AAA from the infrarenal region to the aortic bifurcation around 114.4 mm in length and a maximum sac diameter of 45.1 mm, and dilatation of the right common iliac artery with a diameter of 21.1 mm (Figure 7A).\n\n(A) Pre-procedure CTA. (B) Angiography reveals an infrarenal fusiform aneurysm. (C-F) T&K B-EVAR step-by-step. (G-H) Underexpansion of graft stent. (I-J) Balloon dilatation of main body graft and limb extensions. (K) Evaluation angiography reveals good graft placement and no endoleak. (L) Post-procedure CTA shows good results.\n\nSurgical cutdown was performed on the right and left femoral arteries. Initial aortography revealed an infrarenal fusiform abdominal aortic aneurysm (Figure 7B). A SEAL NOVUS Body Stent Graft 30 (24) × 90 mm 18 × 550 mm (S&G Biotech, Yongin, Korea) was deployed from the ipsilateral femoral access, and subsequently, a SEAL NOVUS limb Stent Graft 12 (20) × 100 mm 15 × 550 mm (S&G Biotech, Yongin, Korea) was deployed in the right common iliac artery. A SEAL NOVUS limb Stent Graft 12 (24) × 100 mm 15 × 550 mm (S&G Biotech, Yongin, Korea) was placed in the left common iliac artery. Aortography evaluation revealed under-expansion of the graft stent, particularly in the main body and areas covering the right common iliac artery (Figure 7C-H). Balloon dilation was performed using a 10 × 46 mm peripheral balloon inflated several times up to 10 cc in the right common iliac artery. The proximal and main body graft stents were expanded using a 10 × 80 mm peripheral balloon catheter and inflated up to 10 cc several times. Double-inflated balloon dilatation was performed using a 10 × 80 mm peripheral balloon catheter, inflated several times at the right and left common iliac arteries (Figure 7I-J). Evaluation aortography showed that the stent was in a good position, with no endoleak and better flow in the left and right iliac arteries (Figure 7K). The total contrast was 180 mL Metacosfar 320, and the dose area product (DAP) was 17.140 Gy.cm2. The fluoroscopy times were 34 minutes and 38 seconds.\n\nAfter six days, the patient was discharged without any complaints. Follow-up CTA approximately 2 weeks after the procedure revealed minimal contrast leakage at the 4th and 5th lumbar vertebrae and a penetrating atherosclerotic ulcer (PAU) in the aortic isthmus (Figure 7L).\n\n\nDiscussion\n\nEVAR has evolved rapidly over the past decade, leading to many advances in configuration and design. Cannulation of the contralateral gate remains one of the most challenging and time-consuming procedures in EVAR deployment, increasing procedural time, radiation exposure, and material costs resulting from any potential bailout strategy.11,12 Even with experienced operators, this rate-limiting step can still be challenging as it requires the most wiring and catheter skills. This is especially relevant as the number of patients with complex aortoiliac anatomy who undergo EVAR continues to increase. Several anatomic features have been reported to prolong the time spent for CGC, namely maximal aneurysm diameter, active thrombus-free lumen, iliac tortuosity, and aortic bifurcation angulation.10 Several experiments have shown a correlation between aortic neck angulation and prolonged CGC. Despite device improvements, it still depends on the operator’s skills and technical expertise.\n\nThe various cases presented highlight the potential universal applicability of the T&K B-EVAR device and method. Of the six reported cases, all had successful outcomes despite the difficult anatomy in some cases. Only one patient in our cohort required an additional adjunctive procedure using a snaring technique from the right brachial access to untwist the contralateral femoral wire. None of the patients experienced serious complications or were discharged with an acceptable LOS. In our case series, difficult cases were reported to have a longer fluoroscopy time and an overall longer procedure time. This finding was consistent with the current literature, which states that a more complex aortoiliac anatomy is associated with an increased procedure time.\n\nCompared to normal bifurcated EVAR, traditional bifurcated EVAR is influenced by many factors, all of which increase contralateral gate cannulation time. Free-hanging bifurcation is susceptible to severe aneurysm neck angulation or highly splayed iliac arteries, which may cause narrowing or bending of gates and require additional adjunctive approaches. T&K B-EVAR offers a sophisticated and simplified approach in which the main body graft fabric extends to encapsulate the bifurcation. In theory, this special design enables easier cannulation, as cannulation is performed on the main body with a larger diameter. This design also means that the positioning strategies normally needed in traditional bifurcated EVAR are no longer required. Furthermore, the graft design offers extra structural support and ballooning of the ipsilateral gate enables easier wiring into the contralateral gate. The extra advantage offered by the device design can enable faster procedure time, reduce fluoroscopy time, and potentially reduce contrast usage and its associated complications, such as contrast-induced nephropathy. The potential reduction in cannulation difficulty also reduces the need for bail-out procedures, which adds to the procedure time and cost. Finally, this device was designed to be universally applicable and can be used in patients with various anatomical features.\n\n\nConclusion\n\nT&K B-EVAR aims to simplify the endovascular AAA repair. The device design enables easier cannulation of the contralateral limb, thereby reducing the procedure time, radiation exposure, and the risk of endoleaks. This technique has been proven to be safe in six patients, reproducible, and potentially universally applicable. However, further research with a larger sample size is needed to validate these results.\n\nWritten informed consent was obtained from the patient for the publication of the case series and accompanying images. We have obtained ethical approval to conduct this study from the National Cardiovascular Center Harapan Kita Hospital.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required. 13\n\nFigshare. CARE checklist for ‘A Revolutionary Device for Endovascular Aortic Repair of Abdominal Aortic Aneurysm: A Pilot Study’. DOI: https://doi.org/10.6084/m9.figshare.23925234.v2 13\n\nData are available under the terms of the Creative Commons Zero “No rights reserved’ data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgements\n\nWe would like to thank the patients for allowing us to publish their cases, and the cardiothoracic surgery and anesthesia teams for their involvement in managing these patients. We would like to thank Edwin Adhi Darmawan Batubara and Kevin Moses Hanky Jr Tandayu from Department of Cardiology and Vascular Medicine, Faculty of Medicine University of Indonesia, National Cardiovascular Center Harapan Kita, University of Indonesia Academic Hospital, Jakarta, Indonesia and Jonathan Edbert Afandy as Research Assistant of Vascular Division, Department of Cardiology and Vascular Medicine, Faculty of Medicine University of Indonesia, National Cardiovascular Center Harapan Kita, University of Indonesia Academic Hospital, Jakarta, Indonesia, Jakarta, Indonesia for their help and support in this research.\n\n\nReferences\n\nKeisler B, Carter C: Abdominal aortic aneurysm. American Family Physician; 2015, April 15.\n\nSong P, He Y, Adeloye D, et al.: The global and regional prevalence of abdominal aortic aneurysms: A systematic review and Modeling Analysis. Ann. Surg. 2022; 277(6): 912–919. PubMed Abstract | Publisher Full Text\n\nChan WK, Yong E, Hong Q, et al.: Systematic Review and meta-analysis of the prevalence of abdominal aortic aneurysm in Asian populations. J. Vasc. Surg. 2021; 73(3): 1069–1074.e1. PubMed Abstract | Publisher Full Text\n\nGolledge J, Thanigaimani S, Powell JT, et al.: Pathogenesis and management of abdominal aortic aneurysm. Eur. Heart J. 2023; 44(29): 2682–2697. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUllery BW, Hallett RL, Fleischmann D: Epidemiology and contemporary management of abdominal aortic aneurysms. Abdom. Radiol. 2018; 43(5): 1032–1043. Publisher Full Text\n\nTenorio ER, Dias-Neto MF, Lima GB, et al.: Endovascular repair for thoracoabdominal aortic aneurysms: Current status and future challenges. ASVIDE. 2021; 8: 326–326. Publisher Full Text\n\nCalligaro KD, Toursarkissian B, Clagett GP, et al.: Guidelines for hospital privileges in vascular and endovascular surgery: Recommendations of the Society for Vascular Surgery. J. Vasc. Surg. 2008; 47(1): 1–5. PubMed Abstract | Publisher Full Text\n\nRehman ZU, Choksy S, Howard A, et al.: Comparison of patient radiation dose and contrast use during EVAR in a dedicated hybrid vascular or and mobile imaging. Ann. Vasc. Surg. 2019; 61: 278–283. Publisher Full Text\n\nKoussayer S, Abuduruk A, Alkhezzi A, et al.: Anatomy-based strategies for contralateral gate cannulation during evar. Ann. Vasc. Surg. 2022; 2(2): 100088. Publisher Full Text\n\nWolf YG, Tillich M, Lee WA, et al.: Impact of aortoiliac tortuosity on endovascular repair of abdominal aortic aneurysms: evaluation of 3D computer-based assessment. J. Vasc. Surg. 2001; 34(4): 594–599. PubMed Abstract | Publisher Full Text\n\nPakeliani D, Lachat M, Blohmé L, et al.: Improved technique for sheath supported contralateral limb gate cannulation in endovascular abdominal aortic aneurysm repair. Vasa. 2019; 49: 39–42. Publisher Full Text\n\nTitus JM, Cragg A, Alden P, et al.: A prospective randomized comparison of contralateral snare versus retrograde gate cannulation in endovascular aneurysm repair. J. Vasc. Surg. 2017; 66(2): 387–391. PubMed Abstract | Publisher Full Text\n\nTaofan: Daftar pasien T&K B-EVAR. [Data set]. National Cardiovascular Center Harapan Kita Academic Hospital; 2023."
}
|
[
{
"id": "314925",
"date": "13 Sep 2024",
"name": "Muhamad Taufik Ismail",
"expertise": [
"Reviewer Expertise vascular medicine",
"peripheral intervention",
"angiologist",
"cardiovascular intervention"
],
"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\nCongratulations on the development of the T&K B-EVAR device, a significant advancement in endovascular aortic repair that enhances the process of contralateral gate cannulation. I have a few suggestions to further strengthen your manuscript:\nProvide a Detailed Comparative Analysis: Include a more comprehensive comparison between the T&K B-EVAR device and existing devices and techniques. This would help to clearly delineate the unique advantages and improvements offered by your device. Discuss the Limitations: Explicitly outline the limitations observed in your cases. A transparent discussion of these limitations will provide a more balanced perspective and help readers assess the broader applicability of your findings.\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? 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 conclusion balanced and justified on the basis of the findings? Yes",
"responses": [
{
"c_id": "12434",
"date": "17 Sep 2024",
"name": "Taofan Taofan",
"role": "Author Response",
"response": "Dear dr. Taofik, Thank you for taking the time to review my article. I greatly appreciate your thoughtful comments and constructive suggestions. Your insights have been invaluable in helping me improve the quality and clarity of the work. I have carefully considered all your feedback and have made the necessary revisions to address the points raised. Once again, thank you for your thorough review and your contribution to enhancing this manuscript. Sincerely, Taofan, Department of Cardiology and Vascular Medicine Universitas Indonesia"
}
]
},
{
"id": "318472",
"date": "16 Sep 2024",
"name": "Elena Giacomelli",
"expertise": [
"Reviewer Expertise vascular 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\nThe authors describe six cases of AAA treated with a new endograft made of a main body stent graft and two limb extensions. The paper is well written; probably the case presentation is redundant and should be shortened. The most important limit of the study is the absence of the definition of the anatomic criteria for inclusion and exclusion. The reasons for using such a technique in the selected cases should be fully described. Moreover it is not clear from the text whether the septum inside the main body extends all over the graft or it is interrupted after a certain numbers of centimeters. This is crucial to understand if adjunctive procedures from the contralateral side are possible or not. Finally the authors should state the reasons why they consider this kind of device really necessary in this era of very complex and advanced endografts allowing the treatment of complex lesions and anatomies. In consideration of this, the claim of the title should be tempered.\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? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the conclusion balanced and justified on the basis of the findings? Partly",
"responses": [
{
"c_id": "12740",
"date": "08 Nov 2024",
"name": "Taofan Taofan",
"role": "Author Response",
"response": "Dear Reviewer, Thank you for your thoughtful and detailed review of our manuscript. We greatly appreciate your constructive feedback, which has provided valuable insights for improving the clarity and scientific rigor of our study. Case Presentation Streamlining We agree with your assessment that certain case details may have been repetitive. In response, we will streamline the case presentations, focusing on the most relevant clinical outcomes and procedural specifics. This will ensure the inclusion of critical information while eliminating unnecessary repetition, enhancing the overall clarity of the manuscript. Indications and Exclusion Criteria This device has been developed primarily to enhance the technical feasibility of EVAR, addressing several limitations observed in current bifurcated designs. We believe it offers a significant improvement in anatomical fit and procedural simplicity, making it suitable for patients with anatomies that may present challenges to conventional devices. Here are the key features that make B-EVAR more feasible: Long Trunk Design and Increased Flexibility: The B-EVAR device features a long trunk type design, which provides greater flexibility compared to current bifurcated designs with shorter main body lengths. This added flexibility enables the device to adapt better to the aorta and iliac arteries, particularly in patients with tortuous anatomy, reducing the risk of device malposition or kinking during deployment. Absence of Bifurcation and Related Complications: The B-EVAR device eliminates the bifurcation point, which is a common source of complications in traditional EVAR. By avoiding the modular connection at the bifurcation, this design reduces the risk of modular leaks and bifurcation kinks, both of which are significant causes of post-procedure failure in standard bifurcated systems. Large Distal Skirt for Easier Contralateral Limb Selection: One of the most critical innovations in the B-EVAR design is the large distal skirt. This feature significantly facilitates contralateral limb selection, a step that can often be technically challenging in bifurcated systems. With the B-EVAR device, the wide skirt allows for easier access and cannulation of the contralateral limb, improving procedural efficiency and reducing overall procedure time, radiation exposure, and contrast usage. Septum Design Clarification Your observation regarding the septum inside the main body of the stent graft is highly appreciated. We have revised the manuscript to specify that the septum extends only into the lower middle portion of the main body and is interrupted after a certain distance. The septum does not extend to the distal portion of the main body. This design allows for adjunctive procedures from the contralateral side when necessary, ensuring procedural flexibility. Necessity of the B-EVAR Device and Title Modification You also inquired about the necessity of this device in an era of highly complex and advanced endografts. While we acknowledge that many sophisticated endografts exist, the B-EVAR device simplifies the often-challenging step of contralateral gate cannulation in complex anatomies. The device’s novel design helps reduce procedure time, radiation exposure, and contrast usage, making it a valuable option in cases where anatomical complexity could prolong the procedure. In light of your suggestion, we have tempered the claim in the title to reflect these considerations more accurately. We believe this approach will pave the way for future EVAR devices that prioritize bidirectional methods over traditional bifurcated systems. Conclusion We hope this clarification provides a better understanding of the indications for using the B-EVAR device. Its flexibility, avoidance of bifurcation-related complications, and ease of contralateral limb selection make it a highly feasible and advantageous alternative to traditional bifurcated EVAR devices. We look forward to your further comments and suggestions, and we thank you again for the opportunity to refine our manuscript. Best regards, Taofan Department of Cardiology and Vascular Medicine Universitas Indonesia"
}
]
}
] | 1
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https://f1000research.com/articles/13-892
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https://f1000research.com/articles/13-595/v1
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07 Jun 24
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{
"type": "Software Tool Article",
"title": "Assessing landscape N removal in coastal New England catchments using the N-Sink approach with the R Package, nsink",
"authors": [
"Dorothy Q Kellogg",
"Jeffrey W. Hollister",
"Chester L. Arnold",
"Arthur J. Gold",
"Emily H. Wilson",
"Cary B. Chadwick",
"David W. Dickson",
"Qian Lei-Parent",
"Kenneth J. Forshay",
"Jeffrey W. Hollister",
"Chester L. Arnold",
"Arthur J. Gold",
"Emily H. Wilson",
"Cary B. Chadwick",
"David W. Dickson",
"Qian Lei-Parent",
"Kenneth J. Forshay"
],
"abstract": "Background Excess nitrogen (N) loading to coastal ecosystems impairs estuarine water quality. Land management decisions made within estuarine watersheds have a direct impact on downstream N delivery. Natural features within watersheds can act as landscape sinks for N, such as wetlands, streams and ponds that transform dissolved N into gaseous N, effectively removing it from the aquatic system. Identifying and evaluating these landscape sinks and their spatial relationship to N sources can help managers understand the effects of alternative decisions on downstream resources.\n\nMethods The N-Sink approach uses widely available GIS data to identify landscape sinks within HUC-12 (or larger) catchments, estimate their N removal potential and map the effect of those sinks on N movement through the catchment. Static maps are produced to visualize N removal efficiency, transport and delivery, the latter in the form of an index. The R package nsink was developed to facilitate data acquisition, processing and visualization.\n\nResults The R package creates static maps for a specific HUC-12, or users can visit the University of Connecticut website to explore previously mapped areas. Users can also investigate specific flowpaths interactively by clicking on any location within the catchment. A flowpath is generated with a table describing N removal along each segment. We describe the motivation behind developing nsink, discuss implementation in R, and present two use case examples. nsink is available from https://github.com/USEPA/nsink.\n\nConclusions N-Sink is a decision support tool created for local decision-makers to facilitate better understanding of the relationship between land use and downstream N delivery. Local decision-makers that have prioritized N mitigation in their long-term planning can use nsink to better understand the potential impact of proposed development projects and zoning variances. Similarly, land trusts and other NGOs interested in N mitigation can use nsink to identify high priority areas for acquisition or restoration.",
"keywords": [
"Nitrogen",
"R",
"watershed",
"catchment",
"GIS",
"landscape N sink",
"water resources",
"nsink"
],
"content": "Introduction\n\nExcess nitrogen (N) delivery via surface water to coastal estuaries contributes to impaired water quality evidenced by excess algal blooms and hypoxia (Ryther and Dunstan 1971, Nixon 1995, Howarth and Marino 2006). Hydrologic connections and flowpaths are influential in the delivery of nutrients to estuaries (Mengistu et al. 2020). Identifying landscape N sinks along hydrologic flowpaths – areas where dissolved N is transformed to gaseous N and effectively removed from the aquatic system – and their effect on N delivery at the watershed scale could provide watershed managers, land use planners and conservation organizations additional strategies that target N reductions. N-Sink, and its associated R package nsink, were developed to be a screening tool that describes the areas or points within a watershed linked with flow paths where downgradient N sinks process and remove excess N, versus areas where downgradient N sinks are less prevalent or less effective at removing N (Hollister et al. 2022, R Core Team 2022). This watershed flow path approach provides a means to easily visualize the relative sensitivity of an area within a watershed that may require more aggressive N management at the source, protection of existing N retentive areas, or restoration and construction of downgradient N retentive areas that are needed to reduce N delivery to estuaries.\n\nN-Sink was developed as a web-based tool to visualize and explore landscape N sinks at the HUC-12 scale (HUC = Hydrologic Unit Code; (Berelson et al. 2004)) and makes extensive use of widely available GIS data. The theoretical underpinnings are outlined in Kellogg et al. (2010) and build on peer-reviewed meta-analyses and reviews (Seitzinger et al. 2006, Alexander et al. 2007, Mayer et al. 2007) to estimate N removal within landscape N sinks – wetlands, streams and ponds. The approach relies on residence time within landscape features that support N removal as the primary driver of N retention and transformation (e.g., Klocker et al. 2009).\n\nThe nsink R package was written to simplify the acquisition and management of the spatial data necessary to estimate N removal within each identified landscape sink, estimate cumulative N removal along a specified flowpath, and create a set of static watershed maps (Hollister et al. 2022). Datasets used by nsink include the National Hydrography Dataset Plus (NHDPlus), Soil Survey Geographic Database (SSURGO), the National Land Cover Dataset (NLCD) land cover and the National Land Cover Dataset (NLCD) impervious surface (Soil Survey Staff 2017, Jin et al. 2019, Moore et al. 2019). The static maps illustrate 1) N Removal Efficiency, a color-coded map of the estimated N removal efficiency of the different landscape sinks; 2) N Transport Index, a heat map with the cumulative N removal along flowpaths originating from sources represented by a grid of points across a watershed. This heat map highlights “leaky” source areas with less downstream N retention versus those with higher downstream retention; and 3) N Delivery Index, combining maps (1) and (2) along with source loading based on NLCD categories and expressed as an index ranging from 0 to 1, resulting in a map showing potential N delivery from different sources, after accounting for the potential N removal as water moves downstream. N-Sink and nsink integrate these data to make the application of complex hydrologic and biogeochemical processes accessible to end users and stakeholders in a visually clear and useful format. Here we describe the development of the package, and example workflow, and simple use applications to demonstrate the capabilities of the tools. The code for the analyses presented here is available from https://github.com/USEPA/nsink_manuscript/ and is archived at https://doi.org/10.5281/zenodo.10045141 (Kellogg et al. 2023). All analyses were conducted with R version 4.2.2 and details on R package versions and operating system used for this analysis are included in a file, sessioninfo.txt at https://github.com/USEPA/nsink_manuscript/blob/main/sessioninfo.txt (Grolemund and Wickham 2011, Xie 2014, 2015, 2023, Pebesma et al. 2016, Wickham 2016, Pebesma 2018, Müller 2020, Hollister et al. 2022, R Core Team 2022, Bocinsky 2023, Hernangómez 2023, Hijmans 2023a, 2023b, Pebesma and Bivand 2023).\n\n\nMethods\n\nThe package nsink implements the approach detailed in Kellogg et al. (2010) to estimate relative nitrogen (N) removal along a flowpath. The nsink package follows from an initial version of N-Sink written in ArcGIS using ModelBuilder. The initial version required time-consuming data manipulation by hand due to limitations of earlier NHDPlus datasets as well as the limitations of working in a GIS environment requiring a user license. With the increasingly more versatile GIS packages now available in R Project for Statistical Computing (RRID:SCR_001905), the previously time-consuming spatial data acquisition and management of N-Sink was automated and applied to other HUC-12 catchments, leading to the development of the nsink package. Specifically, nsink relies on packages sf and terra. The nsink package is available from https://github.com/usepa/nsink and is fully described in (Hollister et al. 2022).\n\nThe nsink package provides several functions (Table 1) to set up and run an N-Sink analysis for a specified 12-digit HUC. By using the package all required data are downloaded, prepared for the analysis, HUC-wide N removal calculated, and flowpaths summarized. Additionally, a convenience function, nsink_build(), is included that will run all of the required functions for a specified HUC. The workflow follows a simple series of steps to create a set of static maps: N Removal Efficiency, N Transport Index, and N Delivery Index.\n\nThe first step for an N-Sink analysis with the nsink package is to download the required datasets. The only required information to download the data is a HUC identifier. The nsink package was developed using 12-digit HUC IDs from NHDPlus, but larger HUCs (e.g. 8-digit) may also be used. There are two functions provided for downloading the data.\n\n• nsink_get_huc_id() - search 12-digit HUC IDs using a known location name.\n\n• nsink_get_data() - download and save, in a specified folder, hydrography, soils, and land cover data for the specified 12-digit HUC. These data cover the HUC, but have not been pared down to those data exclusive to the specified HUC. The nsink package utilizes widely available data from several U.S. Federal Government sources and as of 2023-09-30 no authentication is required to access these sources. The HUC ID is required and users may specify a path for storing the data as well as indicate whether or not to download the data again if they already exist in the data directory.\n\nOnce the data are downloaded there are several additional data processing steps that are required to subset the data to the HUC and set all data to a common coordinate reference system (CRS).\n\nThese include:\n\n• filter out the HUC boundary\n\n• mask all other data sets to the HUC boundary\n\n• convert all column names to lower case\n\n• create new columns\n\n• harmonize raster extents\n\n• set all data to common CRS\n\nThe nsink_prep_data() function will complete all of these processing steps. It requires a HUC ID, a specified CRS, and a path to a data directory. It returns a “list” (a specific data format in R) with all required data for subsequent N-Sink analyses.\n\nThe next step in the N-Sink workflow is to calculate potential nitrogen removal within each landscape sink, expressed as percent of incoming N. Details on how the nitrogen removal estimates are calculated are available in Kellogg et al. (2010), and make use of peer-reviewed literature. Since the publication of that article, changes have been implemented to make better use of the most recently available geospatial data. Those changes are described below. The nsink_calc_removal() function takes the prepared data as an input and returns a “list” with three items:\n\n• raster_method: Contains a raster-based approach to calculating removal. Used for the static maps showing potential N removal within landscape sinks.\n\n• land_removal: Represents land-based nitrogen removal within vegetated hydric soils with impervious surface removed.\n\n• network_removal: Contains removal along the NHD Plus flow network. Removal is calculated separately for streams and waterbodies (i.e., lakes and reservoirs).\n\nA useful part of the N-Sink approach is not just the calculation of potential N removal for individual components of the landscape, it is the ability to summarize cumulative removal along the length of a specified flowpath. Starting from any specified location the flowpath on land is generated from a flow direction grid. Once that flowpath intersects the surface water network, flow is determined by flow along the NHD Plus surface water network. With a flowpath generated, the cumulative N removal along that flowpath can be calculated with the nsink_summarize_flowpath() function, taking the flowpath and removal as input. A data frame is returned with each segment identified by type of sink, if present (i.e., “Hydric”, “Stream”, “Lake/Pond”, or “No Removal”), the percent removal associated with that segment, and cumulative removal. Total cumulative removal is 100 - the minimum of the n_out column. That is, n_out keeps track of the percent of N leaving each subsequent downstream segment (Table 2). Note that the most downstream pond and stream segments show essentially no N removal due to a short retention time.\n\nIndividual flowpaths are useful for specific areas of interest, but it is also useful to look at removal patterns across the landscape. The nsink_generate_static_maps() function produces a set of HUC-wide raster maps. Required inputs are the prepped data, removal raster, and sampling density, for which a default is provided. The function returns four separate rasters.\n\n• removal_effic: HUC-wide estimate of potential nitrogen removal from different landscape sinks as a percentage.\n\n• loading_idx: A normalized index of nitrogen loads by land cover class derived from published sources, ranging from 0 to 1.\n\n• transport_idx: N transport for a sample of all possible flowpaths in a given HUC. This is an expensive computational task, so nsink generates a removal hotspot map based on a sample of flowpaths and the final hotspot map is interpolated from these samples and referred to as the nitrogen transport index. The samp_density argument controls the number of sample flowpaths generated and is roughly the distance between points in a uniform grid. Each of these starting points is assigned the value of N delivery (%) based on cumulative N removal along the flowpath from that starting point. The points are then interpolated with an inverse distance weighted interpolation to a roughly 30 meter resolution. A sampling density of 300 was used to create the static maps in the web application.\n\n• delivery_idx: The delivery index is the combination of the loading index and the transport index. It highlights areas of the landscape that are delivering the most nitrogen to the outflow of the watershed based on NLCD land cover data and transport efficiency.\n\nThese static maps can be quickly plotted with the convenience function nsink_plot() using the map argument to identify map type. For example, nsink_plot(niantic_static_maps, map = \"removal\") will create a plot of Nitrogen Removal Efficiency (Figure 1). The other map argument options are “transport” and “delivery” (Figures 2 and 3). These plots are designed for exploration and not necessarily for high quality maps. For higher quality maps, the source data can be plotted in software of a user’s choice (e.g. QGIS, ggplot2).\n\nN loading estimates are based on land cover classes, making use of peer-reviewed published data, and normalized, with a range of 0 to 1. These N loading factors are then multiplied by the N Transport Efficiency (range 0 to 100) from a given location within a watershed, to arrive at the N Delivery Index.\n\nThe workflow described above includes all the basic functionality. Some users may wish to use nsink to calculate the base layers for an N-Sink analysis and then build an application outside of R. A convenience function that downloads all data, prepare the data, calculates removal, and generates static maps has been included to facilitate this type of analysis. The nsink_build() function requires a HUC ID, coordinate reference system, and sampling density. An output folder is also needed but has a default location. There is an optional argument for forcing a new download. All prepped data shape files and .tif files are written to the output folder for use in other applications.\n\nN-Sink maps are now available for HUC-12 catchments in coastal CT, RI and southern MA as a web application interactive tool. This app can be used to examine and better understand N movement through these HUC-12 catchments.\n\nSeveral improvements have been made to the underlying N-Sink methodology used in Kellogg et al. (2010) that have allowed nsink to make use of more recently available spatial data. In estimating N removal in streams, we originally estimated stream depth and velocity based on other available geospatial data to arrive at a travel time along a given stream reach. With the updated and expanded NHD Plus V2 we use the estimates provided in that dataset, making use of USGS expertise that went into these estimates.\n\nIn estimating N removal occurring in the terrestrial portion of the flowpath, we originally focused on riparian wetlands, using SSURGO mapped hydric soils to identify this landscape sink. With the latest version of SSURGO we include all hydric soils in the catchment, except those identified as “subaqueous”. Each soil mapping unit (SMU) that has a positive hydric status also has an estimate of %hydric for that SMU. We then estimate N removal within that SMU as 80% of the %hydric. Each raster has one SMU associated with it and raster cell size is 30m X 30m. A 30-m wide wetland is estimated by Mayer et al. (2007) as having 80% N removal. In the current version, N removal is cumulative as a flowpath intercepts hydric soils in any cell before encountering surface water.\n\nIn the NHD Plus dataset there are situations where a water body or stream segment is “off-network”, i.e., it is not linked to the larger surface flow network. These may be features such as groundwater-fed kettle ponds, or canals or ditches where connecting hydrology may not be captured in the NHD Plus dataset. These off-network features tend to have less NHD data (e.g., time of travel) associated with them, making direct N removal estimates impossible. In these cases, we must estimate removal based on other in-network surface water features. For the vast majority of HUC-12 catchments off-network features are rare and spatially small compared to the overall system. We examined seven HUC-12s within southern New England, with a range of land cover and soils, for the extent of off-network hydrology. None had off network stream or canal segments, while six of the seven had off-network waterbodies. These off-network waterbodies represented from 2 to 14% (mean of 7%) of total lake area. We estimated removal from off-network stream segments to be equal to the median removal of all first order streams in the same catchment. In this case we are assuming these first order segments behave similarly to other first order stream reaches. A subset of these off-network stream segments is identified by the NHD dataset as ditches and canals. These are expected to provide little N removal due to their designed intent to move water efficiently, reducing residence time (Buchanan et al. 2013), and therefore N-Sink assigns removal as the lower quartile of removal from the highest order streams in the same catchment. Finally, off-network lakes and ponds are assigned N removal at the 3rd quartile of removal from all lakes and ponds in the same catchment due to the level of uncertainty regarding residence time in these groundwater-fed lakes and ponds (Hampton et al. 2019).\n\nN-Sink was designed for catchments where surface and groundwater flow paths are not highly manipulated. In settings where substantial storm water conveyance networks or extensive subsurface agricultural drainage are present, flow can bypass the removal processes within wetland ecosystems (Gold et al. 2001). In these situations, first-order streams may be channelized, leading to higher velocities than in undisturbed channels and the N-Sink estimates of removal may be overstated. N-Sink does not account for nitrogen removal from high permeability (e.g., sand and gravel) unconfined aquifers along the coastal margin. Here, nitrogen-enriched groundwater may enter estuaries directly as submarine discharge rather than via baseflow to stream networks (Nowicki and Gold 2008), requiring site specific assessments to evaluate N removal in salt marshes or as upwelling into the seabed (Addy et al. 2005, Robinson et al. 2018). These situations have been estimated to account for approximately 6% of freshwater inputs to estuaries globally and in areas of New England (Burnett et al. 2003, Nowicki and Gold 2008).\n\nThe variation in loading associated with different agricultural practices, density of unsewered development and inputs from wastewater treatment plants are not encompassed in the default loading index. Thus the numeric outputs of the tool focus on metrics suitable for planning purposes, such as percent removal of N from source to receiving water and relative intensity of loading from different locations. It is not intended to replace high-resolution models that rely on long term weather records and incorporate detailed spatial data on N loading, within-field transport or variable source hydrology (e.g., Easton (2008)). Instead, N-Sink combines widely available datasets for waterway networks, soils and land cover with nitrogen dynamics developed for these datasets to highlight major sources and sinks of nitrogen within a watershed context.\n\nThe R package nsink requires R version >= 3.5.0. The nsink package is available from https://github.com/usepa/nsink and is fully described in (Hollister et al. 2022).\n\n\nUse Cases\n\nUsers can use the following code to interactively identify a starting point for a flowpath of interest.\n\nUsing this approach, we can compare the N delivery from two locations that are separated by approximately 900 meters. This example illustrates the importance of location with respect to landscape N sinks. Approximately 56% of the N that originates at point A is transported to the estuary vs. approximately 25% of the N that originates at point B (Figure 4). The difference is due to the different N sinks encountered along the way to the estuary. Most of the removal that occurs along flowpath A is due to flow through hydric (wetland) soils, with little removal occurring during flow along the downgradient stream network (Table 2). Flowpath B encounters a large pond along the way, significantly increasing residence time and N transformation (Table 3). These two currently undeveloped locations demonstrate the importance of understanding landscape position and its role in the movement of N from source to outlet. If development were proposed in the western portion of this area (flowpath A), source controls could be advised, while the less “leaky” eastern region (flowpath B) underlines the importance of wetlands and slow-moving water ways, such as ponds, that protect downstream waters by slowing flow and increasing opportunities for N transformation.\n\nHydrofeatures are pictured on the Nitrogen Transport Index map.\n\nThe maps produced by N-Sink can help prioritize source controls, sink protection and/or restoration. For example, many wetlands are considered “protected” by federal, state or local laws and regulations; but as occurs with many types of protected areas (Neal et al. 2018) they are frequently altered through variances granted by local commissions or committees charged with zoning decisions. By better understanding the important role that N sinks play in the protection of estuaries, local agencies have a better chance of achieving protection of downstream receiving waters. Variances granted on a case-by-case basis can quickly undermine local water quality goals. Land conservancies and other NGOs interested in identifying parcels of high value for protecting downstream waters from N loading can also use these maps to prioritize land acquisition or wetland restoration projects.\n\nSimilarly, sources of N that are contributing relatively more N due to their location within the catchment can be highlighted using the nsink static maps. The N Delivery Index map combines N sources with N transport to highlight developed areas that are located on “leakier” parts of a catchment. Figure 5A displays a high resolution image of land cover in the same watershed as Example 1, with two developed areas circled. Figure 5B displays the Nitrogen Transport Index map for the same area, showing the western area to be “leakier” than the eastern area.\n\nA. Land cover, summarized in Table 4. B. Nitrogen Transport Index. Hotter colors denote higher values. C. Nitrogen Delivery Index. Darker colors denote higher N delivery based on normalized loading from different land covers, multiplied by the N Transport Index.\n\nAn analysis of N delivery from these two similarly developed areas (average N loading index of developed areas: West = 0.57; East = 0.56), show the western area may contribute more N loading to the estuary than the eastern area, with the average delivery index value of the western area (41) almost 80% higher than the eastern area (23; Figure 5C), suggesting a greater need for N source controls within the western development.\n\nOther examples using N-Sink to examine the N loading implications of past land use decisions are also available as bonus maps on the N-Sink website.\n\n\nDiscussion\n\nN-Sink as implemented in the nsink R package allows users to easily download all necessary spatial data (hydrography, land cover and soils), create static maps (N Removal Efficiency, N Transport Efficiency and N Delivery Index), and interactively investigate N removal along flowpaths within any specified catchment. Currently, the default catchment definition uses HUC-12 designations, though it is also possible to use larger catchments. Larger catchments would require longer download and processing times. For investigators who do not work in R, we have created a web application that covers HUC-12 catchments in coastal CT, RI and southern MA using an interactive tool.\n\nN-Sink is a decision support tool and was created to be a useful, easy way for local land use managers to explore the relationship between land use and nitrogen pollution in their waters. Currently N-Sink is being used as an integral component in a project based in Long Island Sound, funded by the Long Island Sound Study Research Fund. The project is focused on targeting outreach on fertilizer use within the 43,560 km2 catchment. Local decision-makers that have prioritized nitrogen mitigation in their long-term planning efforts can use this tool to help them better understand the potential impact of proposed development projects and zoning variances. Similarly, land trusts and other NGOs interested in N mitigation can use this tool to identify high priority areas for acquisition or restoration.\n\n\nSoftware availability\n\nSoftware available from: https://github.com/usepa/nsink\n\nSource code available from: https://github.com/usepa/nsink\n\nArchived source code at time of publication https://doi.org/10.5281/zenodo.10045141 (Kellogg et al. 2023)\n\nLicense: MIT",
"appendix": "Data availability\n\nDatasets used by nsink include the National Hydrography Dataset Plus (NHDPlus; Moore et al. 2019), Soil Survey Geographic Database (SSURGO; Soil Survey Staff 2017), the National Land Cover Dataset (NLCD) land cover and the National Land Cover Dataset (NLCD) impervious surface (Jin et al. 2019). All are available via the FedData package in R (Bocinsky 2023).\n\n\nAcknowledgements\n\nMany people have contributed in various ways to the development of the N-Sink concept. In particular, we would like to thank Peter August and Chris Damon of the University of Rhode Island’s Department of Natural Resources Science. Additionally, we are grateful to Stephen Shivers, Anne Kuhn, Andrea Bartolotti, Suzanne Ayvazian, and Tim Gleason for constructive reviews of this paper.\n\nThe views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency. Any mention of trade names, products, or services does not imply an endorsement by the U.S. Government or the U.S. Environmental Protection Agency. The EPA does not endorse any commercial products, services, or enterprises. This contribution is identified by the tracking number ORD-054342 of the Atlantic Coastal Environmental Sciences Division, Office of Research and Development, Center for Environmental Measurement and Modeling, US Environmental Protection Agency.\n\n\nReferences\n\nAddy K, Gold A, Nowicki B, et al.: Denitrification capacity in a subterranean estuary below a rhode island fringing salt marsh. Estuaries. 2005; 28: 896–908. Publisher Full Text\n\nAlexander RB, Boyer EW, Smith RA, et al.: The role of headwater streams in downstream water quality 1. JAWRA Journal of the American Water Resources Association. 2007; 43: 41–59. 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Hydrol. 2008; 348: 279–291. Publisher Full Text\n\nGold AJ, Groffman PM, Addy K, et al.: Landscape attributes as controls on groithd water nitrate removal capacity of riparian zones 1. JAWRA Journal of the American Water Resources Association. 2001; 37: 1457–1464. Publisher Full Text\n\nGrolemund G, Wickham H: Dates and times made easy with lubridate. J. Stat. Softw. 2011; 40: 1–25. Publisher Full Text\n\nHampton TB, Zarnetske JP, Briggs MA, et al.: Residence time controls on the fate of nitrogen in flow-through lakebed sediments. J. Geophys. Res. Biogeo. 2019; 124: 689–707. Publisher Full Text\n\nHernangómez D: tidyterra: Tidyverse methods and ggplot2 helpers for terra objects.2023.\n\nHijmans RJ: Raster: Geographic data analysis and modeling.2023a.\n\nHijmans RJ: Terra: Spatial data analysis.2023b.\n\nHollister JW, Kellogg DQ, Lei-Parent Q, et al.: Nsink: An r package for flow path nitrogen removal estimation. Journal of Open Source Software. 2022; 7: 4035–4039. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHowarth RW, Marino R: Nitrogen as the limiting nutrient for eutrophication in coastal marine ecosystems: Evolving views over three decades. Limnol. Oceanogr. 2006; 51: 364–376. Publisher Full Text\n\nJin S, Homer C, Yang L, et al.: Overall methodology design for the united states national land cover database 2016 products. Remote Sens. 2019; 11: 2971. Publisher Full Text\n\nKellogg D, Gold AJ, Cox S, et al.: A geospatial approach for assessing denitrification sinks within lower-order catchments. Ecol. Eng. 2010; 36: 1596–1606. Publisher Full Text\n\nKellogg DQ, Hollister J, Arnold C, et al.: Assessing landscape N removal in coastal New England catchments using the N-Sink approach with the R package, nsink. Zenodo. 2023. Publisher Full Text\n\nKlocker CA, Kaushal SS, Groffman PM, et al.: Nitrogen uptake and denitrification in restored and unrestored streams in urban maryland, USA. Aquat. Sci. 2009; 71: 411–424. Publisher Full Text\n\nMayer PM, Reynolds SK Jr, McCutchen MD, et al.: Meta-analysis of nitrogen removal in riparian buffers. J. Environ. Qual. 2007; 36: 1172–1180. PubMed Abstract | Publisher Full Text\n\nMengistu SG, Golden HE, Lane CR, et al.: Wetland flowpaths mediate nitrogen and phosphorus concentrations across the upper mississippi river basin. JAWRA J. Am. Water Resour. Assoc. 2020.\n\nMoore RB, McKay LD, Rea AH, et al.: User’s guide for the national hydrography dataset plus (NHDPlus) high resolution. US Geological Survey; 2019.\n\nMüller K: Here: A simpler way to find your files.2020.\n\nNeal WJ, Pilkey OH, Cooper JAG, et al.: Why coastal regulations fail. Ocean Coast. Manag. 2018; 156: 21–34. Publisher Full Text\n\nNixon SW: Coastal marine eutrophication: A definition, social causes, and future concerns. Ophelia. 1995; 41: 199–219. Publisher Full Text\n\nNowicki BL, Gold AJ: Groundwater nitrogen transport and input along the narragansett bay coastal margin. Science for Ecosystem-based Management: Narragansett Bay in the 21 st Century.2008; 67–100.\n\nPebesma E: Simple Features for R: Standardized Support for Spatial Vector Data. The R Journal. 2018; 10: 439–446. Publisher Full Text\n\nPebesma E, Bivand R: Spatial Data Science: With applications in R. Chapman and Hall/CRC; 2023; 352.\n\nPebesma E, Mailund T, Hiebert J: Measurement units in R. R Journal. 2016; 8: 486–494. Publisher Full Text\n\nR Core Team: R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2022.\n\nRobinson CE, Xin P, Santos IR, et al.: Groundwater dynamics in subterranean estuaries of coastal unconfined aquifers: Controls on submarine groundwater discharge and chemical inputs to the ocean. Adv. Water Resour. 2018; 115: 315–331. Publisher Full Text\n\nRyther JH, Dunstan WM: Nitrogen, phosphorus, and eutrophication in the coastal marine environment. Science. 1971; 171: 1008–1013. Publisher Full Text\n\nSeitzinger S, Harrison JA, Böhlke J, et al.: Denitrification across landscapes and waterscapes: A synthesis. Ecol. Appl. 2006; 16: 2064–2090. PubMed Abstract | Publisher Full Text\n\nSoil Survey Staff, U: Web soil survey.2017.\n\nWickham H: ggplot2: Elegant graphics for data analysis. New York: Springer-Verlag; 2016.\n\nXie YKnitr: A comprehensive tool for reproducible research in R.Stodden V, Leisch F, Peng RD, editors. Implementing reproducible computational research. Chapman; Hall/CRC; 2014.\n\nXie Y: Dynamic documents with R and knitr. Boca Raton, Florida: Chapman; Hall/CRC; 2nd ed2015.\n\nXie Y: Knitr: A general-purpose package for dynamic report generation in r.2023."
}
|
[
{
"id": "296733",
"date": "10 Aug 2024",
"name": "Jianning Ren",
"expertise": [
"Reviewer Expertise Ecohydrology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn this paper, the authors developed a decision-supporting tool, N-Sink, based on the R package nsink. They described the motivation behind developing nsink, and presented two use case examples of implementing nsink R package. The manuscript is well-written, and the tool can be helpful to local decision-makers. However, I have two main concerns: 1. Since this is a research paper, the author should include some paragraphs discussing how this tool can help with research and the scientific contribution of this research besides helping with decision-making. The web interface is an excellent application; the authors should put some effort into emphasizing this part. So I suggest accept with minor revisions. Below are some detailed comments:\nShould put line numbers in the manuscript The introduction should introduce the N-sink web-based tool earlier with a link and explain the differences between N-sink and nsink The third paragraph, how will the authors deal with the R package issues, such as “raster” package is deprecated and replaced by “terra”. Or how to deal with the version updating issues of R packages. I have tested the N tracker functionality in the web application, there is an error, I suggest to fix this:\" please install the ArcGIS R intergration package R version 4.4.1\" failed to execute N tracker V13\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Partly",
"responses": [
{
"c_id": "12744",
"date": "06 Nov 2024",
"name": "Dorothy Kellogg",
"role": "Author Response",
"response": "Thank you for your very helpful feedback. In response to your two main concerns we have a) added to the narrative to describe ways that the tool can be helpful in resource economics research and provided examples of similar investigations, and b) amended the introduction and overview to better emphasize the web application. Specifically responding to your numbered comments: 1. Alas, we do not have control over the line numbering. 2. We introduce the web application earlier, along with a link, and made changes to the narrative to clarify the differences between N-sink method and the associated R package, nsink. 3. We will be updating the package as changes are made in R. This is an ongoing task with any R package. 4. Thank you for identifying this problem. We have identified the source of the problem and have addressed it. You may confirm that things are working here. Many thanks"
}
]
},
{
"id": "296724",
"date": "23 Aug 2024",
"name": "Lora Harris",
"expertise": [
"Reviewer Expertise coastal ecology"
],
"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\nHaving the nsink tool available in R is a wonderful advancement for this approach to evaluating nitrogen sources in coastal watersheds. I have only minor suggestions to improve description of this tool in this venue.\nThere is a bit of confusion between the title of the article and then the in depth description of nsink itself alongside the published Hollister et al. reference. I am familiar with the Kellogg 2010 work upon which this is based, and in looking at the Hollister reference and github code, I think what I am discerning is that the Hollister et al. (2022) reference is the publication of the actual code, and the hope for this article is that it will showcase how to implement and use the software tool. I believe that there could be some slight improvement to wording to better clarify that. As it stands, the introduction largely introduces nsink rather than the analyses. I believe an additional paragraph or tightening of the third paragraph to clearly transition into setting up the reader to understand the analyses will help to better connect the title, nsink/Hollister et al. (2022) resource, and the work focused on here.\nLikewise, in the methods if there is a way to specify the regional setting for the case study examples or somehow write in a way that clarifies that you are showcasing a case study for the Niantic River, then it will connect better to both the title and resulting figures. Something like an opening paragraph that states clearly that you are presenting a case study for the Niantic River as a way to demonstrate the utility of nsink and that the methods are generalizable to other systems? The Use Cases section doesn't really introduce us to the study location.\nI do really love the caveats section. I think that is so important and useful and I applaud the authors for clearly stating the limitations of the model - all models have limitations and those are best understood by the model creators.\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": "12745",
"date": "08 Nov 2024",
"name": "Dorothy Kellogg",
"role": "Author Response",
"response": "Thank you very much for your thoughtful feedback. In response to your comments: 1. We have changed the title to better reflect the main focus of the article. 2. We have added a brief introduction to the Use Cases describing their location. We have also added to the narrative so that it is clear that this tool can be used in any other appropriate HUC because the data are widely available. Many thanks"
}
]
}
] | 1
|
https://f1000research.com/articles/13-595
|
https://f1000research.com/articles/13-934/v1
|
20 Aug 24
|
{
"type": "Research Article",
"title": "Assessment of early neonatal practices to prevent hypothermia ; A comparative study",
"authors": [
"Smrithi GM",
"Gayathri Renganathan",
"Rohith Motappa",
"Nitin Joseph",
"Ravikiran SR",
"Smrithi GM",
"Rohith Motappa",
"Nitin Joseph",
"Ravikiran SR"
],
"abstract": "Background Globally, neonatal deaths are significantly attributed to hypothermia. This is mostly because of its co-morbidity with asphyxia, premature birth and severe neonatal infections. Worldwide, neonatal hypothermia case fatality rates (CFRs) range from 8.5% to 52%. This study aimed to assess how well a video-based training intervention on mothers’ knowledge and practices in preventing neonatal hypothermia worked.\n\nMethods The knowledge and practices of two groups of primi-para mothers—one control group and one intervention group—were compared in order to achieve this. A total of 124 primipara mothers took part in the research. Using a video based tool, the intervention group was educated about preventing hypothermia in newborns. Both control and intervention group mothers were interviewed to compare the knowledge and practices.\n\nResults Sixty-one of the sixty-two mothers in the control group were unsure of which body area to cover in order to preserve the baby’s body heat. Following the intervention, 61 out of 62 mothers in the group recognised which body part to cover to protect the baby’s body heat. In the post-intervention group, 98.4% of moms wore a cap over their baby’s head, compared to just 35.5% in the control group.\n\nConclusion The results of this study demonstrate the significant improvement in mothers’ knowledge and actions about the prevention of neonatal hypothermia resulting from the use of a video-based training tool.",
"keywords": [
"Neonatal Hypothermia",
"Prevention",
"Video based education",
"Knowledge",
"Practice"
],
"content": "Introduction\n\nA core body temperature of less than 36.5 °C or a skin temperature of less than 36 °C is considered neonatal hypothermia, according to the World Health Organisation (WHO).1 A baby is said to have moderate hypothermia if their temperature is between 32.0 and 34.9°C (89.6 and 96.6°F), and severe hypothermia if it is lower.2 Hypothermia is a significant contributor to newborn fatalities globally, even though it seldom ends in death. This is mainly due to its co-morbidity with severe neonatal infections, premature birth, and asphyxia.3 Hypothermia engenders a vicious cycle with physiological abnormalities such as hypoxia, hypoglycemia and shock.4\n\nEvery year, an estimated four million newborns die.5 Over 99 percent of newborn fatalities take place in underdeveloped nations. One million babies perish in the first month of birth each year, with India alone bearing one-fourth of the burden.6 The case fatality rates (CFR) for newborn hypothermia vary from 8.5% to 52% globally.3 According to a study by Wake et al, neonates with hypothermia had nearly five times the risk of dying as newborns than those with a normal body temperature.6 This study will help achieve the Sustainable Development Goal of the UN, which is to guarantee healthy lives and promote well-being for everyone at all ages.7\n\nTeaching moms how to recognise the symptoms of newborn hypothermia and how to prevent it can be a crucial preventive measure. Only during their hospital stay do newborns have medical supervision. Therefore, it is essential to educate mothers who constantly keep a watch on and tend to the newborn. Researching the effects of maternal education will help reduce newborn hypothermia in general.\n\n\nSummary of evidence\n\nAnurag Srivastava et al. carried out a cross-sectional study among new mothers in Western Uttar Pradesh to ascertain the knowledge and practice gaps on newborn thermal care. It was shown that 60.9% of those surveyed knew exactly how to keep a newborn warm after delivery.8\n\nMahvish Qazi et al. did a study in Northern India on mothers’ awareness of how to prevent neonatal hypothermia. It was shown that while 45% of moms knew how to rapidly wipe a newborn to keep them warm, just 3% of mothers were familiar with kangaroo mother care.9\n\nIn Jimma, South West Ethiopia, a research by Kebede et al. indicated that 32.5% of moms practiced early newborn bathing. Since it causes newborn hypothermia and related problems, this needs to be addressed first.10\n\nNearly half of mothers lack sufficient knowledge about preventing hypothermia, according to a cross-sectional study on the topic conducted by Indu Shah et al. among 70 mothers of newborns.11\n\nIn the SNCU of M.K.C.G Medical College Hospital, 54 mothers of low birth weight neonates participated in a study by Sadhana Panda et al. on their understanding of preventing newborn hypothermia. Just 44% of mothers believed that drying the infant right after would stop heat loss, and only 11% of mothers knew enough about skin-to-skin contact, the most effective way to stop heat loss.12\n\nAccording to a study by Ahmed et al. in three hospitals in the state of Khartoum, only 52.66% of mothers were in favour of treating newborn hypothermia symptoms as soon as they appeared.13\n\nA research by Kibaru et al. in the Nakuru Central district of Kenya found that just 9.7% of mothers recognised hypothermia as a potential danger sign for their newborn.14 According to a research conducted in rural Bangladesh by Zaman et al., hypothermia was the infant risk indication that newly delivered women (RDW) identified the least often(26.1%).15\n\nSmita Srivastava et al.’s randomised control trial found that skin-to-skin contact during the initial postpartum period is associated with improved neonatal temperature regulation.16 Focused interventions reduced the average monthly risk of hypothermia among low birth weight and late preterm neonates to 13.3%, according to research by Christine Andrews et al. Prior to this, the average monthly rate of hypothermia was 29.8%.17\n\nInfants who did not receive their mothers’ first skin-to-skin contact during delivery had a 4.3-fold increased risk of developing hypothermia, as per research by Demissie et al.18\n\nTo determine how well kangaroo mother care (KMC) works to keep low birth weight babies warm while being transported from the hospital to their families, Nimbalkar et al. undertook a study. After being discharged from the hospital, the study group experienced a mean rise in temperature of 0.01°C, whereas the control group saw an average decrease in temperature of 0.07°C during transportation.19\n\nAs part of the intervention plan for their study, Noel Joseph et al. added a number of interventions, such as key cards, hypothermia algorithms, and nursing education. Following implementation, the mother-baby unit’s incidence of hypothermia dramatically decreased, falling from 20.9% to 14.5%. Furthermore, there were 71% fewer newborns who required admission to the Neonatal Intensive Care Unit (NICU).20\n\nMukunya et al.’s multivariable analysis revealed that delayed breastfeeding initiation, low birth weight and home birth were the variables linked to a higher risk of newborn hypothermia.21\n\nAccording to a study by Olawuyi et al., nearly two thirds (66.7%) of mothers in newborn intensive care units were aware of the advantages of Kangaroo Mother Care (KMC).22\n\nIn a research by S P Choudhary et al., which involved medical and paramedical personnel, only 47.8% of the participants correctly defined newborn hypothermia, and a noteworthy 52.2% thought it was an uncommon problem.23\n\nIn the early postpartum period, when neonates are most susceptible to hypothermia, the warm chain was not continuously maintained, according to a study by Karsten Lunze et al done in rural Zambia.24\n\nWithin the first five minutes of birth, 27% of newborns were wrapped and 42% of neonates were dried, according to a study conducted in rural southern Tanzania by Donat Shamba et al. The fact that carers neglected to tend to the baby until after the placenta was delivered was the main cause of the delay in wrapping and drying.25\n\nEarly newborn washing was practiced by 87.5% of women who did not visit health facilities for ANC, compared to 54.8% of moms who had four or more ANC visits, according to Gebrew Getachew et al.26\n\nThe results of a study by Luke Mullany et al showed that infants whose breastfeeding was delayed for longer than 24 hours were almost 50% more likely to experience hypothermia.27 According to a research by Meseret Ekubay et al, 58.3% of mothers started breastfeeding their newborns in the first hour following birth.28\n\nAccording to Golicha Wako et al., out of 388 mothers in South Ethiopia, 69.1% of them covered their newborns’ heads right away after delivery, and almost all of them did so for duration of the neonatal period.29\n\nDongre et al undertook a study to determine how well-informed mothers in periurban Wardha were about infant warning signs. Just 2.8% of respondents identified hypothermia in neonates as one of the warning indicators.30\n\n\nContribution to knowledge\n\nMethods\n\na. Study setting: Postnatal wards of Government Lady Goschen Hospital, Mangalore.\n\nb. Study design: Non Randomized educational Trial.\n\nc. Study participants: Primipara mothers of newborns admitted in the Postnatal wards of Government Lady Goschen Hospital, Mangalore.\n\nGroup A – control group\n\nGroup B – received counselling on preventing neonatal hypothermia via a video-based educational tool\n\nd. Inclusion criteria:\n\nPrimipara Mothers of newborns in the postnatal ward.\n\ne. Exclusion criteria:\n\ni. Mothers of severely ill newborns at the time of data collection.\n\nii. Mothers of babies admitted in NICU.\n\niii. Mothers of babies delivered at home.\n\niv. Inability of mother to participate. Eg: Mother is severely ill at the time of study.\n\nv. Mothers who are not willing to participate.\n\nf. Study duration: 2 months.\n\ng. Sample size: 62 primipara mothers of newborns in the control group and 62 primipara mothers of newborns in the intervention group make up the study’s sample size. Using an article based on new born thermal care as reference, the sample size was determined.8\n\nh. Tool for data collection: A structured questionnaire about preventing hypothermia in neonates.\n\ni. Data collection methodology:\n\ni. From the postnatal wards, participants were chosen. As the control group, Group A did not get any intervention. Using a video-based intervention, Group B was educated on preventing hypothermia in newborns. Group A mothers were recruited between June 24, 2023 and July 24, 2023 and data was gathered. Group B were enlisted and instructed using the video-based tool the following month. Participants’ questions on preventing newborn hypothermia were addressed. The data collection tool was the same questionnaire as used for Group A. Following a review of literature and expert advice, the semi-structured questionnaire was developed. Validation of the content was completed. The principal investigator conducted interviews with the mothers in order to collect data.\n\nii. The principal investigator conducted interviews with both Group A and Group B. Group B was interviewed twenty-four hours after they were educated about preventing neonatal hypothermia. Informed written consent for participation in the study was obtained.\n\nj. Data analysis:\n\nData was entered in Microsoft Excel 2016 (Microsoft Excel, RRID:SCR_016137) and analyzed using SPSS version 25 (IBM SPSS Statistics, RRID:SCR_019096). Data was interpreted in proportions and percentages, and Chi-square and P-values were obtained.\n\nEthical considerations: The Institutional Ethics Committee at Kasturba Medical College in Mangalore has granted ethical clearance on 16/03/23 (Protocol No: IECKMCMLR-03/2023/94). We have received approval from the Government Lady Goschen Hospital’s Medical Superintendent to carry out this research.\n\n\nResults\n\nIn our study there were a total of 124 participants, out of which 50% belonged to the intervention group.\n\nTable 1 depicts the demographic information of study participants which implies that out of 62 mothers in the control group, 5 of them were between the ages of 15-20 years (0.08%), 29 were between 21-25 years of age (46.7%), 19 were between 26-30 years of age (30.6%) and 9 were between 31-35 years of age (14.5%). 51 participants had number of family members ranging between 1-5 (82.3%) and 11 participants had between 6-10 (17.7%). Majority of them had studied between 1st – 10th std (46.8%) and had a family income of Rs.5000-10000 (67.7%) in the control group. Majority of them had a normal vaginal delivery (58.1%) and delivered a term baby (96.8%). Majority of the newborns in the control group were females (56.5%). Out of the 62 newborns in the control group, 6 had a birth weight ranging between 1-1.9 kg (9.7%), 30 between 2-2.9 kg (48.4%) and 26 between 3-3.9 kg (41.9%).\n\nOut of the 62 mothers in the intervention group, 3 of them were between the ages of 15-20 years (4.8%), 27 were between 21-25 years of age (43.5%), 24 were between 26-30 years of age (38.7%) and 8 were between 31-35 years of age (12.9%). 59 participants had number of family members ranging between 1-5 (95.2%) and 3 participants had between 6-10 (4.8%). Majority of the study participants in the intervention group had studied up to higher secondary (41.9%) and had a family income of Rs.10000-15000 (54.8%). Majority of them had a cesarean section (66.1%) and delivered a term baby (98.4%). Majority of the newborns in the intervention group were males (64.5%). Out of the 62 newborns in the intervention group, 2 had a birth weight ranging between 1-1.9 kg (3.2%), 39 between 2-2.9 kg (62.9%) and 21 between 3-3.9 kg (33.9%).\n\nTable 2 shows what mothers know about preventing newborn hypothermia. Of the participants in the control group, 75.8% were unaware of how to maintain the body heat of the newborn, and 91.9% were unsure of which part of the body the baby is most prone to heat loss. This demonstrates that the majority of mothers were ignorant of the need to keep their babies’ bodies warm. 90.3% of participants were unaware of which body parts become cold when a newborn looses heat and 96.8% of participants were unsure of which body part to cover to preserve the infant’s body heat. This data shows that majority of the mothers were not aware of thermal care of the newborn and thus did not know how to prevent neonatal hypothermia. The majority of participants (83.9%) were aware of the best time for the baby’s first bath. Just 21.0% and 29.0%, respectively, knew the best way to dry the newborn after delivery and the ideal time of day to bathe the baby. It may be inferred from this that while a lot of mothers knew when it was best to give their baby their first bath, they were less aware of the best time of day to do so and how to properly dry their infant. Among the participants, a considerable percentage (64.5%) used benzoin resin vapours to dry the baby, indicating that many mothers were unaware that this practice could lead to upper respiratory tract infections in the infant. 75.8% were unaware of how frequently a baby should have their dirty nappy or cloth changed. As wearing a wet, soiled nappy for an extended period of time is one of the causes of hypothermia, unaware mothers put their newborns at risk for the condition. The majority did not know how often the baby should be breastfed (59.7%) or when the newborn needed to start breastfeeding (75.8%). This indicates that most also didn’t know enough about breastfeeding, which is a vital part of preventing hypothermia. Merely 40.3% of them were aware of how frequently a normal baby’s weight should be monitored following delivery. 96.8% of them were aware that the best way to keep body temperature stable just after birth was skin to skin contact. 95.2% of the participants knew which type of bath to follow. It suggests that intervention is not necessary in this case because almost all mothers are aware of the benefits of skin-to-skin contact and the style of bathing that is best for a baby.\n\nPost intervention, 71.0% of the participants understood how to keep the baby’s body temperature stable, and all of them knew which part of the body the newborn is most likely to loose heat from (100%; p-value = 0.000). This demonstrates that mothers’ understanding of newborn thermal care has improved as a result of the video-based intervention. Of the participants, 98.4% (p-value = 0.000) recognised which body part to cover to retain the baby’s body heat, however none of them knew which body parts (0%; p-value = 0.012) get cold when the baby loses heat. Following the intervention, mothers were more informed about which parts of the infant to cover to retain heat, but they lacked sufficient knowledge about which parts of the body get cold in the event of hypothermia. Every participant was aware of the best timing for the baby’s first bath (100%; p-value = 0.001). The majority of them were aware of the best time of day to bathe the infant (64.5%; p-value = 0.000) and the best technique for drying the newborn (72.6%; p-value = 0.000). This proves that the intervention has aided numerous mothers in learning the proper technique to bathe their infants so as not to alter the baby’s body temperature and increase their risk of hypothermia. The majority of participants (95.2%; p-value = 0.000) did not use benzoin resin fumes to dry the baby. Of them, 67.7% (p-value = 0.000) were aware of the frequency of changing a baby’s soiled nappy or cloth. This indicates that mothers were also instructed on the usage of benzoin fumes and the importance of changing dirty diapers often as part of the video-based intervention. The majority of women knew when to start breastfeeding a newborn (85.5%; p-value = 0.000) and how often to do so (77.4%; p-value = 0.000), suggesting that the intervention had enhanced mothers’ breastfeeding knowledge. Of them, 80.6% (p-value = 0.000) were aware of the frequency of weight checks for a normal baby. The intervention has led to a significant number of mothers to know how often the baby’s weight should be checked.\n\nResponses to questions on ideal time of the day for baby’s bath, changing soiled diapers and breastfeeding in Table 2 were similar to responses found by Leilane Barbosa de Sousa et al on their study on effect of educational video on newborn care knowledge among mothers.31 Knowledge of mothers about newborn’s first bath, drying the baby and initiation of breastfeeding in Table 2 were similar to results found in a study by Richard Mangwi et al.32\n\nResponses to questions on best method to maintain body temperature immediately after birth and type of bath to be preferred was found to be statistically insignificant, showing that the mothers had adequate knowledge regarding this and do not require an intervention.\n\nMothers’ preventive measures against neonatal hypothermia are shown in Table 3. Seventy-seven percent of the mothers in the control group did not wrap their baby with a shirt, cap, gloves, socks, nappies, or towel. The majority of them (95.2%) do not examine the baby’s legs and abdomen for heat loss and (64.5%) do not cover the baby’s head with a cap. This demonstrates that most mothers do not sufficiently cover their babies and do not routinely check for neonatal hypothermia danger signs. 83.9% of them lie down in bed with their baby next to them, suggesting that a large number of the mothers engaged in skin-to-skin contact. 90.3% of women do not clean their breasts before breastfeeding. This indicates that the majority of mothers do not nurse with proper hygiene, leaving baby susceptible to diseases. Only breastfeeding is provided for the infant by 71.0% of mothers, and in 98.4% of these cases, the majority of the areola and nipple are in the baby’s mouth during feeding. A sizable percentage of mothers ensure appropriate attachment throughout breastfeeding and provide exclusive breastfeeding. 100% of the babies slept well after feeding. This demonstrates that every mother gave her baby an appropriate breastfeed.\n\nFollowing the intervention, 53.2% of the mothers dressed their baby in a shirt, cap, gloves, socks, diaper and towel (p-value = 0.000). The majority of them checked the baby’s legs and abdomen for heat loss (74.2%; p-value = 0.000) and covered the baby’s head with a cap (98.4%; p-value = 0.000). Making mothers adequately cover their babies has been a successful outcome of the intervention. Additionally, it has effectively prompted most mothers to look for warning signs in their newborns. This will encourage prompt medical attention, preventing the potentially fatal effects of neonatal hypothermia. Every mother lies down in bed with her baby (100%; p-value = 0.001), indicating that the intervention has improved mothers’ practices regarding skin-to-skin contact. Before breastfeeding, the majority of women clean their breasts (54.8%; p-value = 0.000). 100% of the babies slept soundly after feeding. Enhancing hygienic breastfeeding practices and ensuring adequate breastfeeding have been made possible by the video-based intervention.\n\nPractices regarding adequately covering the baby, identifying danger signs of neonatal hypothermia and adequate breastfeeding were similar to results found by Swathi Eluri et al.33 Practices of mothers on skin to skin contact, exclusive breastfeeding and hygienic breastfeeding practices in Table 3 were comparable to results found by Laura Subramanian et al.34\n\nIntervention group had better exclusive breastfeeding practices as compared to control group, but not statistically significant. This data indicates that the mothers were practicing exclusive breastfeeding and an intervention is not required for that. This finding was similar to results found by B. Adhisivam et al in a study assessing the impact of a video based health education program.35\n\n\nCritical reflection\n\nOf the 124 moms who took part in our study, 97.6% of them gave birth to a term child. The intervention increased mothers’ knowledge from 24.2% to 71.0% regarding how to maintain their baby’s body heat. Mothers in the intervention group knew when to start breastfeeding at a rate of 85.5%, compared to just 24.2% of mothers in the control group.\n\nFollowing the intervention, mothers’ practices for controlling the newborn’s body temperature, maintaining skin-to-skin contact, and exclusively breastfeeding showed considerable improvement. In the control group, 75.8% of mothers were unaware of the appropriate time to start breastfeeding. 85.5% of mothers knew when to start breastfeeding their newborn after the intervention.\n\nIn the post-intervention group, 98.4% of mothers wore a cap over their baby’s head, compared to just 35.5% in the control group. Mothers’ knowledge and practices towards preventing neonatal hypothermia have improved as a result of the intervention, as seen by improvements in exclusive breastfeeding and newborn thermal care.\n\n\nDiscussion\n\nThis study found that the video based intervention has been effective in improving the knowledge of mothers about breastfeeding, ideal time of the day for baby’s bath and changing of soiled diapers. This finding was consistent with the study done by Leilane Barbosa de Sousa et al in Brazil.31 The intervention has helped mothers learn about initiation of breastfeeding, drying of the newborn and the baby’s first bath. These results aligned with those found by Richard Mangwi et al in Uganda.32\n\nWe found that the video has been successful in improving good neonatal practices such as exclusive breastfeeding, thermal care of newborn, hand hygiene and recognising danger signs in newborn. These finding were comparable to the study conducted in Mangalore by Swathi Eluri et al.33 Post intervention, skin to skin contact, exclusive breastfeeding and hygienic breastfeeding practices among mothers had improved, which was similar to results found by Laura Subramanian et al in India.34\n\nBetter exclusive breastfeeding practices were observed in the intervention group as compared to the control group, but it was not statistically significant. This result indicates that most mothers were practicing exclusive breastfeeding and an intervention is not required for that. This was in line with results found by B. Adhisivam et al in South India.35\n\nThe study was conducted only among primipara mothers with normal newborns and studies involving educating multipara mothers, mothers with severely ill newborns and mothers of newborns admitted in NICU may by required. This study was conducted in a public institution in an urban area. Hence further studies in public and private institutions of rural and urban areas are recommended.\n\n\nConclusion\n\nThe results of this study demonstrate the significant improvement in mothers’ knowledge and practices about the prevention of neonatal hypothermia due to the use of a video-based educational tool. Consequently, it will result in a decrease in mortality and morbidity rates of neonates related to hypothermia.\n\n\nEthics and consent\n\nThe Institutional Ethics Committee at Kasturba Medical College in Mangalore has granted ethical clearance on 16/03/23 (Protocol No: IECKMCMLR-03/2023/94). We have received approval from the Government Lady Goschen Hospital’s Medical Superintendent to carry out this research.\n\nInformed written consent for participation in the study was obtained.",
"appendix": "Data availability statement\n\nFigshare: (Hypothermia FINAL DATA Excel), https://doi.org/10.6084/m9.figshare.26378965.v1. 36\n\nFigshare: Questionnaire and Consent form.docx, https://doi.org/10.6084/m9.figshare.26402773.v1. 37\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgment\n\nMedical Superintendent, Government Lady Goschen Hospital, Mangalore.\n\nDr. Suchetha S Rao, Professor and Head of Department, Department of Paediatrics, KMC Mangalore.\n\n\nReferences\n\nBeletew B, Mengesha A, Wudu M, et al.: Prevalence of neonatal hypothermia and its associated factors in East Africa: a systematic review and meta-analysis. BMC Pediatr. 2020; 20: 148. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWHO: Thermal control of new born. Maternal and safe motherhood programme 2003.\n\nLunze K, Bloom DE, Jamison DT, et al.: The global burden of neonatal hypothermia: systematic review of a major challenge for newborn survival. BMC Med. 2013 Jan 31; 11: 24. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMathur NB, Krishnamurthy S, Mishra TK: Evaluation of WHO classification of hypothermia in sick extramural neonates as predictor of fatality. J Trop Pediatr. 2005 Dec; 51(6): 341–5. Epub 2005 Jul 13. PubMed Abstract | Publisher Full Text\n\nLawn JE, Osrin D, Adler A, et al.: Four million neonatal deaths: counting and attribution of cause of death. Paediatr Perinat Epidemiol. 2008 Sep; 22(5): 410–416. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWake GE, Chernet K, Aklilu A, et al.: Determinants of neonatal mortality among neonates admitted to neonatal intensive care unit of Dessie comprehensive and specialized hospital, Northeast Ethiopia; An unmatched case-control study. Front Public Health. 2022 Sep 27; 10: 979402. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUnited Nations: Transforming Our World: The 2030 Agenda for Sustainable Development. New York: UN Publishing; 2015.\n\nSrivastava A, Saxena S, Srivastava P, et al.: Newborn thermal care in western Uttar Pradesh—gap analysis between knowledge and practices. Arch Public Health. 2022 Dec; 80(1): 1. Publisher Full Text\n\nQazi M, Saqib N, Raina R: Knowledge regarding prevention of hypothermia in newborns among mothers in Northern India. Int J Res Med Sci. 2019; 7: 1727–1732. Publisher Full Text\n\nFenta Kebede B, Dagnaw Genie Y, Yetwale Hiwot A, et al.: Early Newborn Bath Practice and Its Associated Factors in Jimma, South West Ethiopia, 2021. Pediatric Health Med Ther. 2022 Mar 5; 13: 43–52. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShah I, Paudyal L, Soti H, et al.: Descriptive Cross-sectional Study on Mothers’ Knowledge Regarding Prevention of Neonatal Hypothermia. Journal of Universal College of Medical Sciences. 2022; 10: 62–66. Publisher Full Text\n\nPanda S, Majhi B, Panda A: KNOWLEDGE REGARDING PREVENTION OF HYPOTHERMIA AMONG MOTHERS OF LBW NEONATES IN SNCU OF M.K.C.G. MEDICAL COLLEGE HOSPITAL. J Evid Based Med Healthc. 2017; 4: 5054–5057. Publisher Full Text\n\nMohammed Ahmed NSO, Al-Gamar EA: Mother’s knowledge and attitude regarding recognition of neonatal signs of danger. Sudan J Paediatr. 2022; 22(1): 27–35. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKibaru EG, Otara AM: Knowledge of neonatal danger signs among mothers attending well baby clinic in Nakuru Central District, Kenya: cross sectional descriptive study. BMC Res Notes. 2016 Oct 25; 9(1): 481. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZaman SB, Gupta RD, Al Kibria GM, et al.: Husband’s involvement with mother’s awareness and knowledge of newborn danger signs in facility-based childbirth settings: a cross-sectional study from rural Bangladesh. BMC Res Notes. 2018 May 9; 11(1): 286. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSrivastava S, Gupta A, Bhatnagar A, et al.: Effect of very early skin to skin contact on success at breastfeeding and preventing early hypothermia in neonates. Indian J Public Health. 2014 Jan-Mar; 58(1): 22–26. PubMed Abstract | Publisher Full Text\n\nAndrews C, Whatley C, Smith M, et al.: Quality-Improvement Effort to Reduce Hypothermia Among High-Risk Infants on a Mother-Infant Unit. Pediatrics. 2018 Mar; 141(3): e20171214. Epub 2018 Feb 14. PubMed Abstract | Publisher Full Text\n\nDemissie BW, Abera BB, Chichiabellu TY, et al.: Neonatal hypothermia and associated factors among neonates admitted to neonatal intensive care unit of public hospitals in Addis Ababa, Ethiopia. BMC Pediatr. 2018 Aug 4; 18(1): 263. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNimbalkar S, Popat V, Patel P, et al.: Effect of Kangaroo Mother Care Transport in Preventing Moderate Hypothermia in Low Birth Weight Babies During Transportion to Home After Discharge: A Randomized Controlled Trial. Indian Pediatr. 2023 Apr 15; 60(4): 272–276. Epub 2023 Jan 9. PubMed Abstract | Publisher Full Text\n\nJoseph N, Dror T, Takhalova E, et al.: A quality improvement initiative to reduce hypothermia in a Baby-Friendly nursery - our story of algorithms, K-cards, and Key cards. J Perinatol. 2021 Jul; 41(7): 1760–1768. Epub 2021 May 13. PubMed Abstract | Publisher Full Text\n\nMukunya D, Tumwine JK, Nankabirwa V, et al.: Neonatal hypothermia in Northern Uganda: a community-based cross-sectional study. BMJ Open. 2021 Feb 11; 11(2): e041723. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlawuyi O, Ezenwa BN, Fajolu IB, et al.: Knowledge, attitude and practice of kangaroo mother care among mothers in the neonatal wards of a tertiary care center. Pan Afr Med J. 2021 Apr 14; 38: 364. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChoudhary SP, Bajaj RK, Gupta RK: Knowledge, attitude and practices about neonatal hypothermia among medical and paramedical staff. Indian J Pediatr. 2000 Jul; 67(7): 491–496. PubMed Abstract | Publisher Full Text\n\nLunze K, Yeboah-Antwi K, Marsh DR, et al.: Prevention and management of neonatal hypothermia in rural Zambia. PLoS One. 2014 Apr 8; 9(4): e92006. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShamba D, Schellenberg J, Hildon ZJ, et al.: Thermal care for newborn babies in rural southern Tanzania: a mixed-method study of barriers, facilitators and potential for behaviour change. BMC Pregnancy Childbirth. 2014 Aug 11; 14: 267. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGetachew G, Ibrahim IM, Mulugeta Y, et al.: Early newborn bathing and associated factors among mothers in Afar Region, Northeast Ethiopia. J Trop Pediatr. 2022 Dec 5; 69(1): fmac117. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMullany LC, Katz J, Khatry SK, et al.: Neonatal hypothermia and associated risk factors among newborns of southern Nepal. BMC Med. 2010 Jul 8; 8: 43. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEkubay M, Berhe A, Yisma E: Initiation of breastfeeding within one hour of birth among mothers with infants younger than or equal to 6 months of age attending public health institutions in Addis Ababa, Ethiopia. Int Breastfeed J. 2018 Jan 23; 13: 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWako WG, Beyene BN, Wayessa ZJ, et al.: Assessment of neonatal thermal cares: Practices and beliefs among rural women in West Guji Zone, South Ethiopia: A cross-sectional study. PLOS Glob Public Health. 2022 Jun 15; 2(6): e0000568. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDongre AR, Deshmukh PR, Garg BS: Awareness and health care seeking for newborn danger signs among mothers in peri-urban Wardha. Indian J Pediatr. 2009 Jul; 76(7): 691–693. Epub 2009 Apr 16. PubMed Abstract | Publisher Full Text\n\nSousa LB, Braga HFGM, Alencastro ASA, et al.: Effect of educational video on newborn care for the knowledge of pregnant and postpartum women and their families. Rev Bras Enferm. 2021 Nov 10; 75(Suppl 2): e20201371. English. Portuguese. PubMed Abstract | Publisher Full Text\n\nMangwi Ayiasi R, Kolsteren P, Batwala V, et al.: Effect of Village Health Team Home Visits and Mobile Phone Consultations on Maternal and Newborn Care Practices in Masindi and Kiryandongo, Uganda: A Community-Intervention Trial. PLoS One. 2016 Apr 21; 11(4): e0153051. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEluri S, Baliga BS, Rao SS, et al.: Can Flip-Chart Assisted Maternal Education Improve Essential New Born Care Knowledge and Skills? A Randomized Controlled Trial. Matern Child Health J. 2022 Sep; 26(9): 1891–1906. Epub 2022 Apr 6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSubramanian L, Murthy S, Bogam P, et al.: Just-in-time postnatal education programees to improve newborn care practices: needs and opportunities in low-resource settings. BMJ Glob Health. 2020 Jul; 5(7): e002660. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAdhisivam B, Vishnu Bhat B, Poorna R, et al.: Postnatal counseling on exclusive breastfeeding using video - experience from a tertiary care teaching hospital, south India. J Matern Fetal Neonatal Med. 2017 Apr; 30(7): 834–838. Epub 2016 May 26. PubMed Abstract | Publisher Full Text\n\n[Dataset]. Smrithi GM, Rohith M: Hypothermia FINAL DATA Excel.xlsx. Dataset. figshare. 2024. Publisher Full Text\n\nSmrithi GM: Questionnaire and Consent form. [Dataset]. figshare. Thesis. 2024. Publisher Full Text"
}
|
[
{
"id": "320822",
"date": "25 Sep 2024",
"name": "Linus Olson",
"expertise": [
"Reviewer Expertise Hyper- and hypothermia for neonates",
"Infections public health in LMIC countries",
"treatment with HT for HIE"
],
"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 an interesting article. The article shows that we need to use interactive tools and videos as well as multiple training sessions.\nThere are many things in results that are discussion material and needs to be moved down (As a reviewer, I don’t want to go into the details here since I would advise the authors that the whole manuscript should be rewritten).\nThere are though some References discussing how communication is done in a closed loop way that should be added. (The technique of closed loop discussions go hand in hand with this manuscript so the authors have many to choose of and since there are culture differences in what you prefer using I choose not to give an example in this review report)\nI suggest to rewrite it in less statement in method and more as a scientific article.\n\nThe filming and video tools used is not described well enough. The type of camera, resolution and how they where used (blinded/masked for the group being filmed or not), how the videos were presented on a TV or a screen or in a bigger audience is not clear and what equipment used.\nAll of this influence the learning concept for the mothers especially if they are in a crises or stress and since this is an important study that can have a big impact on how we teach and tell things it is of great importance for possible replications by others later.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12578",
"date": "17 Oct 2024",
"name": "Smrithi null",
"role": "Author Response",
"response": "Author Response Smrithi GM Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India Dear reviewer, We are very thankful for the availability and willingness of an international reviewer such as yourself to help us in peer review of the article titled “Assessment of early neonatal practices to prevent hypothermia ; A comparative study”. We have carefully considered your valuable feedback and have made efforts to improve the clarity and focus in our manuscript as per you suggestions and have made the changes accordingly. 1. Reviewer’s Comment : “There are many things in results that are discussion material and needs to be moved down (As a reviewer, I don’t want to go into the details here since I would advise the authors that the whole manuscript should be rewritten).” Response : The format of the article has been re-written with the result section being made concise and discussion material shifted under appropriate heading. 2. Reviewer’s Comment : “There are though some References discussing how communication is done in a closed loop way that should be added. (The technique of closed loop discussions go hand in hand with this manuscript so the authors have many to choose of and since there are culture differences in what you prefer using I choose not to give an example in this review report)” Response : We have addressed the methodology and explained in detail the materials used to communicate with and educate the mothers. In regards to communication, our video was made to enable a closed loop communication where we had clear objective of a set of points to educate the mothers. The information was clearly communicated in the language best understood and any questions asked following the video were addressed and followed up the next day prior to conducting the post intervention interview (ensuring closed loop communication). 3. Reviewer’s Comment : “I suggest to rewrite it in less statement in method and more as a scientific article. The filming and video tools used is not described well enough. The type of camera, resolution and how they where used (blinded/masked for the group being filmed or not), how the videos were presented on a TV or a screen or in a bigger audience is not clear and what equipment used.” Response : The methodology has been rewritten in less statement and more according to a scientific article. The key points like how the video was prepared, and used (as single blinded) and how it was presented have been elaborated in methodology. 4. Reviewer’s Comment : “All of this influence the learning concept for the mothers especially if they are in a crises or stress and since this is an important study that can have a big impact on how we teach and tell things it is of great importance for possible replications by others later.” Response : Regarding the learning concept of the mothers, we have included only the mothers who have had an uneventful pregnancy and were of sound mind to participate in the study because we had to interview them pre and post video intervention. Any mothers who had any complications or seemed to be in stress due to pain or any other reasons had been excluded as they fulfil the exclusion criteria “inability of the mother to participate” of the study. Once again, we appreciate your valuable feedback, and if you have any further comments or suggestions to improve the article, we will be happy to address them."
}
]
},
{
"id": "316697",
"date": "01 Oct 2024",
"name": "Pracheth Raghuveer",
"expertise": [
"Reviewer Expertise Mental Health",
"Non-Communicable Diseases",
"Health Systems 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\nI congratulate the authors for a timely study focusing on assessment of early neonatal practices to prevent neonatal hypothermia. However, there are a few reservations. 1. Rationale or need for study is missing. The authors are advised to incorporate it. 2. The methods need improvement. Instead of going for points, it is advisable to explain the methods in sentences. 3. In the results, I suggest it is better to present some of the key factors associated with early neonatal practices. 4. Discussion needs significant improvement. It is essential to compare the key findings with other studies, provide a balanced summary of the findings and highlight the strengths, novelty. 5. Ethics section has appeared twice in the manuscript.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? 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": "12579",
"date": "17 Oct 2024",
"name": "Smrithi null",
"role": "Author Response",
"response": "Author Response Smrithi GM Kasturba Medical College Mangalore, Manipal Academy of Higher Education, Karnataka, Manipal, 576 104, India. Dear reviewer, Thank you for taking time to review our article. We appreciate your feedback and would like to address your observation and inform you that the following changes have been done. 1. Reviewer’s comment : “Rationale or need for study is missing. The authors are advised to incorporate it.” Response : Rationale for need of study has been added after Summary of Evidence. 2. Reviewer’s comment : “The methods need improvement. Instead of going for points, it is advisable to explain the methods in sentences.” Response : We have revised and reviewed the article thoroughly and the methodology has been rewritten in the appropriate format as per your suggestion. 3. Reviewer’s comment : “In the results, I suggest it is better to present some of the key factors associated with early neonatal practices.” Response : As per your suggestions, the results have also been rewritten to include only the key factors associated with early neonatal practices. The remaining points have been discussed under Discussion. 4. Reviewer’s comment : “Discussion needs significant improvement. It is essential to compare the key findings with other studies, provide a balanced summary of the findings and highlight the strengths, novelty.” Response : Discussion has been reviewed and updated. The key findings have been compared with other studies and the strengths have been highlighted in the critical reflection as per your suggestion. 5. Reviewer’s comment : “Ethics section has appeared twice in the manuscript.” Response : We have removed the additional Ethics section which had been repeated in the manuscript. Once again, we appreciate your valuable feedback, and if you have any further comments or suggestions to improve the article, we will be happy to address them."
}
]
}
] | 1
|
https://f1000research.com/articles/13-934
|
https://f1000research.com/articles/13-1325/v1
|
05 Nov 24
|
{
"type": "Research Article",
"title": "Water quality evaluation by WQI and ICOs for the rivers of Joya de los Sachas and Francisco de Orellana",
"authors": [
"Diego Vacili Burbano Salas",
"Freddy Ajila",
"Maria Paulina Poma Copa",
"Daniel A. Lowy",
"Diego Vacili Burbano Salas",
"Freddy Ajila",
"Maria Paulina Poma Copa"
],
"abstract": "A monitoring program enabled the evaluation of water quality and the simulation of the pollution dynamics of the rivers in the Joya de los Sachas and Francisco de Orellana cantons in Ecuador. For this assessment one used the WQI (water quality index) and the pollution indices ICOMO (organics contamination), ICOSUS (suspended solids), ICOMI (mineralization), ICOTRO (trophy system), and ICOpH (pH Index). The mathematical model operates with several input parameters, including dissolved oxygen, fecal coliforms, the biochemical oxygen demand (BOD5), turbidity, total solids, total phosphorus, pH, total nitrogen, suspended solids, alkalinity, conductivity, temperature, and the concentrations of nitrates, nitrites, and phosphates. WQI values were obtained from ICO pollution indices. The pollution of the Sacha area is significant, WQI = 0.292, which represents an advanced degree of pollution, since increased BOD values correspond to a high load of organic pollutants. They can originate from household, agricultural, industrial, and soil erosion waste. Likewise, the Sacha River has an ICOSUS = 0.16, which renders water treatment difficult, without impacting human health. Calculated WQI values reveal that the water quality of the Sacha, Basura and Coca rivers is low, being highly contaminated. In contrast, the Huamayacu, Jivino Rojo, Jivino Negro, and Jivino Blanco rivers are commonly polluted.",
"keywords": [
"Ecuador rivers",
"river water quality",
"ICOMI",
"ICOMO",
"water pollution index",
"and water quality index (WQI)"
],
"content": "Highlights\n\n\n\n• Water quality of Ecuadorian rivers.\n\n• Use of water quality index (WQI).\n\n• Application of pollution indices ICOMO, ICOSUS, ICOMI, ICOTRO, and ICOpH.\n\n• Pollution dynamics of rivers in the Joya de los Sachas and Francisco de Orellana cantons.\n\n\nIntroduction\n\nFreshwater quality today is an important concern of the habitats, as they are exposed to pollution originating from natural and anthropogenic sources (Singh et al. 2020), including agricultural and industrial agents (Aristizabal-Tique et al. 2024), namely, agricultural runoff and untreated sewage (Kumar & Mishra 2024). Agriculture pollutes waters through the often-excessive application of fertilizers, composts, and pesticides, as well as by animal farming activities, incorrect irrigation practices, deforestation, and aquaculture (Anh et al. 2023). Among industrial discharges, one should primarily mention industrial waste. Also, one cannot neglect the increasing quantity of household garbage.\n\nNatural causes may play an unwanted role, like biodegradation of plant and animal parts in clear water (Bhosale et al. 2023), and natural events, which trigger erosion processes, such as siltation arising from riverbank erosion (Wu et al. 2024). Therefore, aquatic ecosystems are exposed to threats. One should emphasize that these ecosystems are the most valuable and at the same time the most vulnerable habitats in the world (Ribeiro et al. 2021).\n\nHumankind is confronted with the severe problem of scarcity of fresh water in rivers and lakes, which are exposed to pollutants produced by anthropic activities (Gleick & Cooley 2021). Water quality relates to different uses therefore, it is important to collect quantitative information on the concentrations of organic, inorganic (Teunen et al. 2021), radiological (Asaduzzaman et al. 2022), and microbiological parameters of water (Anggun et al. 2024).\n\nBased on the above theoretical assessment, the authors have identified several factors that affect inadequate water management in Ecuador. Among them, one should mention the scarcity of biophysical information, the absence of planning in agro-productive and industrial activities, the shortage of rural development agencies, and the sectionally organized governments.\n\nAccording to data from the National Institute of Statistics and Censuses (INEC) of Ecuador in 2020 a total of 5.2 million hectares were allocated to agricultural activities in the country. Such a large agricultural area demands an extensive use of agrochemicals. Because of bad practices, one uses an excessive quantity of pesticides. The latter constitutes a major pollutant; pesticides spread because of runoff and erosion severely affecting water quality. Beyond doubt, this endangers the cleanliness of surface water, human health, and the environment. The agricultural activities in the Joya de los Sachas area have intensified considerably over the years 2008-2015 owing to the drop in oil prices and the utilization of large native forest areas. Another identified problem is hydrocarbon activity, like in Block 60 where oil spills occurred. 58% of the oil spills happened in the parishes of San Carlos, and 42% in the parish Unión Milagreña, where four private companies and one public company function. These are environmental management companies, which handle hazardous wastes of the oil industry. Therefore, rivers are highly polluted.\n\nAs reported in previous studies, several toxic metals are present in the Basura, including Cu, Cd, Ni, and Pb; Estero INIAP contains Cu, Ni, Pb, and TPH; Yanayacu has Cu, Ni, and Pb; Blanco identified the presence of TPH, while copper (Cu) was found in Sacha also known as the Quinchayacu River. There are significant problems of water pollution in the parishes Unión Milagreña with 66.2%, San Sebastián del Coca with 56.5%, and Enokanqui with 47.6% of the total available water (Rocha-Gutiérrez et al. 2015; Lorenzo et al. 2016).\n\nThe main reason for establishing a monitoring program is to check the physical, chemical, and biological parameters of rivers in the project area, and to rate, whether they represent a climate-smart production system. Also, one aims to determine synergies between mitigation, adaptation, and food security measures implemented since 2017 by the Causana Yachay Group. To establish such synergies, one should document that they meet requirements for agricultural use, conservation of aquatic life, and recreation (Asaduzzaman et al. 2022).\n\nTo assess water quality, representative indicators should be considered, which enable a comprehensive analysis of the state of rivers (Torres et al. 2010). A widely used tool is the ICA water quality index (WQI) which identifies the quality trends by considering physicochemical, biological, and non-aquatic aspects. One evaluated the quality of river waters via mathematical models that revealed the approximate quality parameters at points where the water was monitored from October 2019 to February 2020. Models were used to simulate the dynamics of pollutants and compare different rivers. In addition, the natural variables of aquatic ecosystems (Gleick & Cooley 2021, Torres et al. 2010, Morin-Crini et al. 2022) were tracked over time.\n\n\nMethods\n\nThe study area of this project included the experimental farms of the examined components in the Parishes San Carlos, San Sebastián del Coca, Tres de Noviembre, San José de Guayusa, the Joya de los Sachas and Francisco. Investigated were the experimental farms of Orellana components, in the Province of Orellana, which correspond to an area of 1205.6 km2. Four reference points have been selected for sampling on the Sacha River and Basura River experimental estates.\n\nOne sampled and characterized river water at the monitoring points to assess the water quality and simulate the pollution dynamics of the Joya de los Sachas canton for agricultural use, preservation of aquatic life, and recreation. Subsequently, one performed calculations and analysis of quality indices WQI, ICOMO, ICOSUS, ICOpH, ICOTRO, and ICOMI.\n\nThe sampling points were selected by considering the use of oil, anthropogenic activities close to the rivers, and the accessibility, width, and depth of the rivers. By this approach, the authors designated 5 monitoring points at the Sacha River, 5 at the Basura River, 6 at the experimental farms assigned to zootechnics, and 5 at the sector for agronomy. At each monitoring point, one carried out an integrated sampling, according to the following criteria: for rivers over 10 m wide 1 sampling point was chosen for every 2 m of the river width (Morales-Guzmán et al. 2022; Castle 2015), and a total of 21 points were monitored. To obtain better representativeness of the water bodies’ quality, the samples were collected monthly, from October 2019 to February 2020, to coincide with the rainy and dry seasons (Alvarez et al. 2019). In each of the 21 points one determined: dissolved oxygen (DO), turbidity, dissolved total solids, pH, alkalinity, conductivity, temperature, and the concentration of three ions: ammonium (NH4+), nitrates (NO3-), and nitrites (NO2-). All data were collected with the multiparameter meter HI 9829 (Hanna Instruments, Ltd., Bedfordshire, England). The coliforms were measured utilizing Petrifilm® plates (Neogen, Lansing, Michigan, USA), following the procedure below: (i) the samples were diluted in a ratio of 1:10 with distilled water, (ii) then the sample was homogenized and (iii) with the help of a volumetric pipette of 1.0 mL the sample was sown onto the plate, and lastly, (iv) the plate was incubated in a stove at 105 °C. To measure phosphates a Compact photometer PF-12Plus (MACHEREY-NAGEL, Inc., Allentown, Pennsylvania, USA) was used and the 0-80 Nano colors test was conducted with reference 984 080. The biochemical oxygen demand (BOD5) was analyzed by the test method ITE-AQLAB-07 (AQLAB Laboratorios Acosta y Compañía, Ecuador), with reference HACH 8000.\n\nThe WQI measure was used to evaluate water quality. First, the parameters were selected and then a mathematical equation was developed (see Eq. 1). The WQI value varied from 0 to 10, where “0” represented the lowest quality and “10” the highest. Value ranges were assigned to the obtained WQIs (Miranda et al. 2016). Hence, WQI of 9.0-10.0 means excellent water quality, 7.0-9.0 represents good water quality, the 5.0-7.0 range corresponds to regularly contaminated waters, 2.5-5.0 is highly contaminated water, while 0.0-2.5 relates to an oversaturation of contaminants when the water resource is practically dead (see Table 1). All experimental data and the related calculations are available in the Dryad repository (Lowy 2024).\n\nSource: The authors’ ellaboration based on Google Maps.\n\nTherefore, the selected parameters are grouped according to the organic load (BOD5), recovery effect (expressed as dissolved oxygen, DO), fecal coliforms (FC), and aesthetic aspects (ST, turbidity) as dependent variables, while nutrients NO3- and PO43- are considered independent variables (Koch et al. 2023). The WQI factor weights are based on the importance of each parameter for human health, the environment, and the organoleptic properties of the water. For the variables in Eq. 2, the weighting factors commonly used for comparison are the following: a = 1, b = 1.7, c = 1.5, d = 1.6, e = 1, f = 1, g = 1.2, and h = 1.\n\nTo calculate the pollution rate based on the performed monitoring, six pollution indices (ICOs) shall be used: the mineralization pollution index (ICOMI), which in its turn considers 3 parameters (conductivity, hardness, and alkalinity), the organic matter contamination index (ICOMO), BOD5, total coliforms, percent of dissolved oxygen in water (%DO), suspended solids contamination (ICOSUS), total phosphorus contamination (ICOTRO), and the pH pollution index (ICOpH). The latter parameter is based on the pH and the temperature pollution index (ICOTEMP), i.e., the temperature of the receiving body and the pouring (Lorenzo et al. 2016, Gil-Marín et al. 2018). Also used is the ICAUCA index, a water quality index adapted from the WQI NSF, Dinius, CETESB, and ICOSUS indices (Torres et al. 2010). ICAUCA considers the chemical, physical, and microbiological parameters, including %DO, Fecal coliforms, Turbidity, BOD5, Total solids, pH, Total phosphorus, and Total nitrogen for the weighting of each parameter of ICAUCA. The weightings of all these parameters are listed in Table 2, developed for tropical rivers.\n\nThe obtained values were compared with those listed in Table 3, the latter corresponding to the water quality classification according to the ICAUCA value. Several equations shall be used for the calculation of pollution indices: ICOMI, which represents the average value of the three chosen variables, all being defined in the range from 0 to 1, where zero “0” indicates very-low contamination, while values close to the unity “1” correspond to very high contamination (see Eq. 3).\n\nWhen the conductivity values are greater than 210 μS cm−1, the conductivity index takes the value ICOND = 1; for hardness values that exceed 110 ppm, the hardness index will be IHARD = 1. For a hardness less than 30 ppm, the hardness index is IHARD = 0. When the alkalinity is equal to or greater than 250 ppm, the alkalinity index value becomes IALK = 1, and for lower alkalinity, one has IALK = 0 (Asaduzzaman et al. 2022, Trikoilidou et al. 2017).\n\nFor Equation 4 to calculate ICOMO, the values greater than BOD of 30 g m−3 correspond to a biochemical oxygen demand index IBOD = 1; if BOD is less than 2 g m−3, IBOD = 0.\n\nWhen the total coliforms are greater than 20,000 NMP.100 cm−3 the ITOT COL = 1, while in case the total coliforms are less than 500 NMP.100 cm−3, ITOT COL = 0. If the percent of oxygen is greater than 100%, then IO% = 0. Therefore, in chaotic systems, percent-saturations greater than 100% indicate re-aeration of water resources; in lentic systems, this reflects the eutrophication problem (Gil-Marín et al. 2018).\n\nThe ICOSUS calculation was performed according to Eq. 5. One considers that suspended solids greater than 340 g m−3 correspond to ICOSUS = 1, while suspended solids less than 10 g m−3 are assigned an ICOSUS = 0.\n\nFor the ICOTRO calculations, values between 0 and 1 are determined, where the total phosphorus concentration defines the oligotrophic <0.01 g m−3, mesotrophic 0.01–0.02 g m−3, eutrophic 0.02–1 g m−3, and hypereutrophic >1 g m−3 waters.\n\nICOpH calculations were performed based on Eq. 6, where contamination values of 0 and 1 are assigned to the low and high limits of the pH scale (Mokhtar et al. 2021). When Eq. 7 was used for the calculation of ICOTEMP, at a temperature difference (ΔT) less than 2.5 °C, the ICOTEMP value was 0, and when ΔT was greater than 15.0 °C the assigned ICOTEMP value was equal to the unity.\n\n\nResults and Discussion\n\nIn total 16 parameters were monitored to calculate contamination rates for the analyzed samples. These parameters were ICOMO, ICOSUS, ICOPH, ICOTRO, and ICOMI, the latter being derived from values of conductivity, hardness, and alkalinity (see Table 4).\n\nThe Sacha, Basura, Coca, Huamayacu, Jivino Rojo, Jivino Negro, and Blanco Chico rivers presented low ICOMI values, except for the Jivino Negro River, which has a greater value (this parameter is related to hardness). The ICOMO pollution rate with values as high as 0.292 can be explained by correlating the rate of trophic contamination with the rate of contamination by organic matter already present in the river. A phenomenon of eutrophication originating from the high phosphorus content was revealed. The analysis concluded that because of this phenomenon, the amount of organic matter in the water increased the biological demand for oxygen, generating an oxygen shortage in the environment. Therefore, the excess nutrients and organic matter deteriorate water quality, as revealed in Figure 2a; Figure 2b shows the quantification of phosphorus in the water samples. Figure 2c documents how fecal coliforms were analyzed, while Figure 2d is a picture taken during NO3- and PO43- measurements.\n\na. Jivino Negro River eutrophic quality, b. Total P determination in the laboratory, c. Determination of fecal coliforms, d. Determination of NO3- and PO43-.\n\nThe ICOpH values, on the 0-1 to 1-0 scale (Quality-Pollution), were determined for the Sacha, Coca, Basura, Huamayacu, Jivino Rojo, Jivino Negro, and Blanco Chico rivers. On the scale established for this parameter (Ramos-Pacheco et al. 2023) they all present low ICOpH values, which reveals that the water quality of these rivers is not altered. This means that no corrosion problems are expected in the pipes. Nonetheless, pH adjustment is needed because of the coagulant used in the flocculation-coagulation stage. Doing so will enable efficient water purification. The ICOSUS parameter, which indicates the suspended solid contamination rates of the Sacha, Coca, Basura, Huamayacu, Red Jivino, Black Jivino, and Blanco Chico rivers arise from a low half-basin, as displayed in Figure 3a. The phosphorus concentration in water affects the Hash Pollution Index (ICOTRO) shown in Figure 3b.\n\nTherefore, the Sacha, Red Jivino, Black Jivino, Coca, and Basura rivers are of eutrophic quality, a phenomenon caused by an excessive concentration of dissolved or suspended nutrients in the water. Plants and organisms are abundant; upon dying they deplete the water quality. By contrast, mesotrophic quality presents a certain abundance of nitrogen and phosphorus. Nevertheless, Huamayacu and Blanco Chico rivers remain of desirable quality.\n\nWastewater discharges, solid waste, and uncontrolled spills of hydrocarbons are likely responsible for pollution. From the comparison of ICOs pollution rates, one assigns the Sacha River the value of 0.292, the highest relative to the other rivers investigated in this study; it corresponds to an elevated degree of pollution. Increased BOD values reveal the presence of a large load of organic pollutants, which can originate from household, agricultural, industrial, or soil erosion waste. Likewise, the Sacha River has an ICOSUS value of 0.16, the highest of the rivers examined here. It causes problems when it enters through the pipes of the water purification system; fortunately, it does not pose any health issues, not affecting the daily activities of people.\n\nThe water quality of the Sacha, Basura, and Coca Rivers, characterized by the water quality index, WQI, assesses high contamination, the Huamayacu, Jivino Rojo, Jivino Negro, and Blanco Chico rivers being regularly contaminated (Koch et al. 2023). The identified problems are related to the hydrocarbon activity of Block 60, where several oil spills happened. Examples include accidental oil spills, which occurred in the parishes of San Carlos and Unión Milagreña (reported above). In these places 4 private companies and one public company operate, all being environmental managers, which handle the hazardous waste in the oil industry (Table 5).\n\nThe results reported in this paper document water quality when remarkable anthropic activity and a strong incidence of contamination are present. The observed chemical, microbiological, and physical parameters show local variations at certain points in the aquatic systems. Wastewater discharges, solid waste, and uncontrolled spills of hydrocarbons (oils) are likely responsible for the contamination of these rivers. The comparison of ICOs pollution rates reveals that Sacha River has an ICO = 0.292, which is the highest of the investigated rivers. This value corresponds to an advanced degree of pollution since increased values of BOD indicate a strong load of organic pollutants. Likewise, the Sacha River has an ICOSUS value of 0.16, the most elevated of all the examined rivers. Nonetheless, it does not pose problems in water treatment, and it does not affect the health or the daily activities of people who get in touch with the water.\n\nThe pollution problem of the Sacha, Basura, and Coca rivers is severe and constitutes a concern, as according to our WQI results, these rivers are significantly contaminated. The pollution was mainly caused by the hydrocarbons-related activity in Block 60, where oil spills were reported. It is alarming that most oil spills occurred in the San Carlos parish and in the Unión Milagreña parish. This demonstrates that the environmental management of companies in this area is not effective, therefore, these companies cause severe damage to the water quality of nearby rivers. In April 2000, shortly after the timeframe of the water quality monitoring reported in this paper, a major oil spill occurred in the Ecuadorian Amazon, which severely polluted the Coca River. It affected the area over the entire year, posing serious health problems to the indigenous Kichwa (Flores & Josefsen Hermann 2020). This harsh event demands for urgent measures taken by the authorities in charge to control and prevent pollution in this area. Oil companies must comply with environmental standards and be held accountable for the harm caused to the ecosystem. Furthermore, it is essential to strengthen surveillance and to monitor oil-related activities to prevent new spills and environmental damage. It is also important to involve and motivate the community in protecting the rivers and to encourage local people to report polluting activities. The health of people and the ecosystem depends largely on water quality, so it is vital to reverse environmental decay, and to act for securing a beneficial and safe environment. As revealed by WQI values, the investigated Ecuadorian rivers are polluted. Basura River contains Cu, Cd, Ni, and Pb; Estero INIAP has Cu, Ni, Pb, and TPH; pollutants of Yanayacu River are Cu, Ni, and Pb; Blanco contains TPH, while Sacha or Quinchaya has toxic Cu. The water in the parishes is also contaminated: Unión Milagreña parish with 66.2%, San Sebastián del Coca with 56.5% and Enokanqui with 47.6% of the total water available in natural surface water sources (Rocha-Gutiérrez et al. 2015; Lorenzo et al. 2016).\n\n\nConclusions\n\nSampling and 4-point analysis were carried out on the experimental farms. Seven points in specific settlements, 5 points in the Sacha River, and 5 points in the Basura River, which correspond to the sampling points, identified with the names of the owners and belonged to the Sacha, Huamayacu, Jivino Rojo, Jivino Negro, Coca, and Garbage rivers. From October 2019 to February 2020, 6 rivers in the Joya de los Sacha Canton and 1 river in the Francisco de Orellana Canton were examined.\n\nThe ICO pollution rate of Sacha River was found 0.292. This is the highest value among the investigated rivers, and corresponds to a significant degree of pollution, since increased BOD indicates a strong load of organic pollutants originating from household, agricultural, industrial, and soil erosion waste. Likewise, the Sacha River has an ICOSUS value of 0.16, the most elevated of the examined rivers. This poses corrosion problems, when water enters the pipes for water treatment, as the moving solid particles act as abrasives, wearing down the metal surface of the pipes, weakening the pipe wall, and making it more susceptible to chemical corrosion. Fortunately, it does not pose health problem and does not affect the daily activities of people, who get in contact with the water.\n\nThe pollution index study represents an easy-to-understand quantitative assessment, which conveys important information of water quality and pollution. An advantage of this method is that it integrates and correlates essential parameters via straightforward equations. Among the considered parameters one finds water hardness, total coliforms, and the total amount of phosphorus present in water. After completing the calculations, one can effortlessly interpret the process, since the values from 0 to 1 provide a good estimate of the other indices.\n\nThe water quality was described quantitatively by the water quality index (WQI) and yielded the following classification: (i) the Sacha, Basura and Coca rivers are highly contaminated, while (ii) the Huamayacu, Jivino Rojo, Jivino Negro, and Blanco Chico are regularly contaminated. Importantly, the authors seek to provide incentive, support, and continuity to similar studies, since they provide useful data to improve the general environmental conditions of the province of Orellana. These findings can also promote and generate new legislation that would serve to regulate all company activities in the area. Results reported here also recommend good practices for farmers, who dispense bodies of water. Such streams can yield minimum amounts allowed for the content of potentially harmful substances over the dumping and, in general, can stimulate the dissemination of the results obtained in such studies.\n\n\nEthics statement of the authors\n\nThe research reported in this manuscript did not involve human participants and no animals were used.\n\nOur manuscript adheres to the reporting standards: the submitted manuscript is accurate and objective. The authors have written an entirely original research article, and the work and/or words of others have been appropriately cited or quoted. No permissions were needed. Proper acknowledgment of the work of others was given, all information contained in the manuscript is cited properly. No privately obtained information was used or reported. No forms of plagiarism are present in the submitted manuscript. No information obtained in the course of confidential services was used. Neither this paper, nor its topic have been submitted for consideration in another journal. Authorship is limited to exclusively the four named authors who have contributed to the conception, design, execution, or interpretation of the reported study. No other experts have contributed to the article.\n\nComprehensive data availability statement: all data collected and processed in this paper are available in the following repository.",
"appendix": "Data availability\n\nDyrad: River water quality measurement in Ecuador, DOI: https://doi.org/10.5061/dryad.2ngf1vhz7 (Lowy 2024).\n\nThis project contains the following underlying data:\n\n• README.md – Abstract of the project, Description of the data and file structure, list of variables used in the paper, Methods: Study Area, Methodology, Sampling and characterization of monitoring points.\n\n• River_water_quality_in_Ecuador.xls – Excel file with all data acquired over the research.\n\nData is available under the terms of the Creative Commons CC0 Universal license (CC0 1.0).\n\n\nAcknowledgment\n\nThe authors thank the authorities of the Escuela Superior Politécnica de Chimborazo Sede Orellana for supporting the implementation of equipment and materials in the laboratory, which enabled the analysis of water samples. We appreciate the farm owners, who granted access to their facilities, and we praise the contribution made by seventh-grade students of the Department of Environmental Engineering, from September 2019 to March 2020, who collaborated in monitoring and taking water samples from the rivers.\n\n\nReferences\n\nAlvarez M, Philip C, Vasquez G: 2019 Evaluation of the quality of surface water bodies around the San Ramon mining project (Red Eagle) applying GIS and QUAL2KW tools. Monografía Especialización en Medio Ambiente y Geoinformática (Monograph of Specialization in Environment and Geoinformatics). Universidad de Atioquia; June 2019. [Accessed: 6th June 2024]. Reference Source\n\nAnggun Zuhaida A, Widodo A, Prima EC, et al.: River Water Quality Analysis Using Arduino-Based Sensor of the Cikapundung River, Indonesia. iJOE Int. J. Online Biomed. Eng. 2024; 20: 30–47. Publisher Full Text\n\nAnh NT, Can LD, Nhan NT, et al.: Influences of key factors on river water quality in urban and rural areas: A review. Case Stud. Chem. Environ. Eng. 2023; 8: 100424. Publisher Full Text\n\nAristizabal-Tique VH, Gómez-Gallego DM, Ramos-Hernández IT, et al.: Assessing the Physicochemical and Microbiological Condition of Surface Waters in Urabá-Colombia: Impact of Human Activities and Agro-Industry. Water Air Soil Pollut. 2024; 235(4): 260. Publisher Full Text\n\nAsaduzzaman K, Priya FJ, Akter D, et al.: Radiological risk assessment of farm-raised fish species due to natural radionuclides in the freshwater ecosystem of Bangladesh with the statistical approach. Radiation Effects and Defects in Solids. 2022; 177(5–6): 432–454. Publisher Full Text\n\nBhosale R, Pathare S, Bhosale R, et al.: A Review Paper on Water Pollution in Rivers of the City. Int. J. Res. in Appl. Sci. Eng. Technol. (IJRASET). 2023; 11(5): 7210–7215. Publisher Full Text\n\nCastle G: Toxicological Tests and Water Quality Assessment Methods.2015; Vol. 53. 9788578110796.\n\nCastro M, Almeida J, Ferrer J, et al.: Indicators of water quality: evolution and trends at the global level. Ing. Ambient. 2014; 10: 111–124. Publisher Full Text\n\nFlores CE, Josefsen CE, Hermann L: Months after an oil spill in the Ecuadorian Amazon, the Kichwa’s water remains polluted. Lifegate. 2020 Dec. 31; 2020. (Accessed: June 26, 2024). Reference Source\n\nGil-Marín JA, Biscay C, Montaño-Mata NJ: Assessment of surface water quality using the Water Quality Index (ICA). Case study: Guarapiche River Basin, Monagas, Venezuela. An. Scientists. 2018; 79: 111–119.\n\nGleick PH, Cooley H: Freshwater Scarcity. Annu. Rev. Environ. Resour. 2021; 46: 319–348. Publisher Full Text\n\nKoch S, Bianchi V, Grutka SA, et al.: Diagnosis of water quality in an urban wetland. Revista de Gestão Social e Ambiental. 2023; 17(2): e03225–e03225. Publisher Full Text\n\nKumar M, Mishra GV: Causes and Impacts of Water Pollution on Various water bodies in the State of Rajasthan, India: A Review. Environ. Ecol. 2024; 42: 645–654. Publisher Full Text\n\nLorenzo-Márquez H, Torres-Dosal A, Barba Macías E, et al.: Estimation of risk of exposure to heavy metals by consumption of plecos (Pterygoplichthys spp.) in infants of riverside communities of ríos the Grijalva and Usumacinta rivers, Mexico. Rev. Int. Contam. Ambient. 2016; 32: 153–164. Publisher Full Text\n\nLowy D: River water quality measurement in Ecuador. [Dataset]. Dryad. 2024. Publisher Full Text\n\nMiranda R, Paul J, Mosquera S, et al.: Quality indexes on surface water bodies in the planning of water resources. Indices of quality surface water bodies in the planning of water. Logos, Hundred & Technology. 2016; 8: 159–167.\n\nMokhtar K, Boualem B, Layachi G: Hydrochemical Characterization and Water Quality of the Continental Intercalare Aquifer in the Ghardaïa Region (Algerian Sahara). J. Ecol. Eng. 2021; 22(10): 152–162. Publisher Full Text\n\nMorales-Guzmán G, Ferrera-Cerrato R, Rivera-Cruz M d C, et al.: Phytoremediation of soil contaminated with weathered petroleum hydrocarbons by applying mineral fertilization, an anionic surfactant, or hydrocarbonoclastic bacteria. Int. J. Phytoremediation. 2022; 25(3): 329–338. Publisher Full Text\n\nMorin-Crini N, Lichtfouse E, Liu G, et al.: Worldwide cases of water pollution by emerging contaminants: a review. Environ. Chem. Lett. 2022; 20(4): 2311–2338. Publisher Full Text\n\nRocha-Gutiérrez BA, del Rosario Peralta-Pérez M , Zavala-Díaz de la Serna FJ: Global review of the problem of the emerging contaminants. PBDEs in Mexico, a particular case. Revista Internacional de Contaminación Ambiental. 2015; 31(3): 311–320.\n\nRamos-Pacheco BS, Choque-Quispe D, Ligarda-Samanez CA, et al.: Water Pollution Indexes Proposal for a High Andean River Using Multivariate Statistics: Case of Chumbao River, Andahuaylas, Apurímac. Water. 2023; 15(14): 2662. Publisher Full Text\n\nRibeiro S, Limoges A, Massé G, et al.: Vulnerability of the North Water ecosystem to climate change. Nat. Commun. 2021; 12: 4475. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSingh J, Yadav P, Pal AK, et al.: Water pollutants: Origin and status. Sensors in water pollutants monitoring: Role of material (Part of the book series: Advanced Functional Materials and Sensors, AFMS). 2020; pp. 5–20. Publisher Full Text\n\nTeunen L, De Jonge M, Malarvannan G, et al.: Effect of abiotic factors and environmental concentrations on the bioaccumulation of persistent organic and inorganic compounds to freshwater fish and mussels. Sci. Total Environ. 2021; 799: 149448. PubMed Abstract | Publisher Full Text\n\nTorres P, Cruz CH, Patiño P, et al.: Applying water quality indexes (WQI) to use of water sources for human consumption. Inginiería e Investigación. 2010; 30(3): 86–95. Publisher Full Text\n\nTrikoilidou E, Samiotis G, Tsikritzis L, et al.: Evaluation of water quality indices adequacy in characterizing the physico-chemical water quality of lakes. Send it. Process. 2017; 4: S35–S46. Publisher Full Text\n\nWu X, Zhang Z, Cai C, et al.: Soil type regulates the divergent loss characteristics of sediment associated carbon and nitrogen in different size classes during rainfall erosion on cultivated lands. J. Environ. Manage. 2024; 354: 120479. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "344444",
"date": "16 Jan 2025",
"name": "Masoud Hussein Hamed",
"expertise": [
"Reviewer Expertise Environmental",
"water",
"soil",
"air pollution",
"waste water treatment",
"ecology and risk assessment"
],
"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 has been accepted and includes innovative research focusing on the Joya River. However, I recommend enhancing the quality of the included figures to ensure they effectively convey the research findings and support the study’s conclusions. Additionally, it would be beneficial to incorporate recent and relevant literature to provide a more comprehensive context for the research. This will not only strengthen the manuscript's credibility but also align it with the current state of knowledge in the field\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": "13158",
"date": "17 Jan 2025",
"name": "Daniel A. Lowy",
"role": "Author Response",
"response": "On behalf of the Authors I would like to thank Professor Masoud Hussein Hamed for his valuable comments and useful recommendations! Given that river water quality if of high environmental impact and the pollution of river waters may cause significant health problems to the population, the authors intend to continue their research and to keep monitoring river waters in a continuous and sustainable manner. Our next account will incororate, indeed, Professor Hamed's suggestions."
}
]
}
] | 1
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https://f1000research.com/articles/13-1325
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https://f1000research.com/articles/13-1322/v1
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05 Nov 24
|
{
"type": "Research Article",
"title": "Determinants of child marriage among rural women in the West Guji Zone, Southern Ethiopia, 2024: a community-based cross-sectional study",
"authors": [
"Shiferaw Gelchu",
"Dessalegn Wirtu",
"Merga Dheresa",
"Dessalegn Wirtu",
"Merga Dheresa"
],
"abstract": "Background of the study Child marriage is linked with multiple maternal and child health issues. However, there is insufficient information regarding the factors influencing child marriage among rural women.\n\nObjective To identify the determinants of child marriage among rural women of reproductive age women in the West Guji Zone, Southern Ethiopia, 2024.\n\nMethods A community-based cross-sectional study was conducted from April 1 to May 5, 2024. A multistage sampling procedure was used to select 711 participants. The SPSS version 25 was used for data analysis. A multivariable logistic regression model was fitted to determine the determinants of child marriage. Adjusted odd ratio with a 95% confidence interval was used to assess the strength of the associations, and statistical significance was declared at p < 0.05.\n\nResults The prevalence of child marriage was 49.6% (95% CI: 0.472-0.524). Being Muslim (AOR=2.104, 95% CI =1.176-3.764), nonformal fathers’ education (AOR=2.633, 95% CI=1.135-6.109), primary level of fathers’ education (AOR=3.326, 95% CI=1.421-7.787); not exposed to media (AOR=1.56, 95% CI=1.033-2.356); living with a relative (AOR=1.592, 95% CI=1.012-2.504); not knowing the legal age of marriage (AOR=2.528, 95% CI=1.593-4.010); marital decision making by girls (AOR=.666, 95% CI=.463-.959), and poor parental wealth status (AOR=4.464, 95% CI=2.795-7.129) were associated with child marriage.\n\nConclusion Almost one in every two women married before 18 in the study area. The determinant factors include religion, fathers’ level of education, exposure to media, living arrangements; awareness of the legal marital age, marriage decision making, and parents’ wealth status. Thus, intervention efforts should focus on these factors to increase the marital age and improve women’s prospects.",
"keywords": [
"Child marriage",
"rural women",
"determinants",
"West Guji"
],
"content": "Introduction\n\nAge at first marriage has a significant effect on women’s prospects. Child marriage is a widespread cultural tradition globally and involves the marriage of girls under the age of 18 years.1 Marriage before the age of eighteen is regarded as a discriminatory practice that violates human rights and exposes women to numerous challenges.2 Marriage at an early age is associated with a lower level of education, dissatisfaction with married life, poor physical and mental health outcomes, a lack of autonomy, increased gender inequality, marital insecurity, divorce, a low status of women in society, curtailed economic empowerment, limited access to job opportunities, and a higher fertility rate.3–5 In contrast, marriage at a later age than 18 years has been correlated with higher rates of female involvement in the labor force, improved mother and child health, more bargaining power, higher levels of education, and lower fertility rates.6\n\nA report by the United Nations Children’s Fund (UNICEF) states that more than 650 million women and girls alive today were married before turning 18.7 More than half 55.11% of women in sub-Saharan Africa are married at a young age less than18 years old.8 Among them, Eastern and Southern Africa is home to about 32%. With 17.3 million early-married women, Ethiopia is the leading country in the region.7\n\nGlobally, there was an increase in the mean age at first marriage among women between 1995 and 2015 from 22.3 years to 23.3 years.6 In Western countries, between 1965 and 2000, the mean age of marriage improved from 24.7 to 28.3 years.9 Similarly, the proportion of women married before 18 years of age has declined over the past three decades from 1 in 3 girls to 1 in 4 girls.10 In Sab-Saharan Africa (SSA) from 1950-2005, there was an increase in marital age of 3.3 years in urban areas and 1.1 years in rural areas.11 Nonetheless, the region as a whole had a 55.11% prevalence of early marriage, with a range of 28.11% in Burundi to 80.77% in Niger.8 Similarly, in Ethiopia, the mean age of first marriage among women improved from 14.34 years in 2000 to 15.5 years in 2016.12 However, Ethiopia remains one of the top ten countries in the world in terms of the number of girls married at an early age.10\n\nChild marriage is associated with several factors, including women’s education status, employment opportunities, family wealth status, family size,8 religion,13 living in rural areas, knowledge of legal marital age,14 marriage decision making,15 ethnicity, exposure to media,16,17 lack of alternative options for girls rather than marriage, absence of supporting agencies, social norms, fear of pregnancy,18 maternal education,19 lack of awareness of the legal age of marriage,20 feelings of loneliness,21 an unsecured environment, conflict within the family, the presence of fragmented families22 and stigma associated with girls’ virginity,23 which are factors that influence early marriage.\n\nEliminating cultural practices that affect women’s health, such as marriage before the age of 18 is a national and international concern. According to Sustainable Development Goal (SDG) 5.3, early marriages should cease by 2030,24 and Ethiopia pledged to end under 18 marriages by 2025.25 However, more than half (56.34%) of Ethiopian girls married before turning 18 years.26 Moreover, research has revealed that rural women are more likely to marry at an early age than urban women, and experience the negative effects of doing so.20,26 Arranged marriages are more common in the research area than love marriages are, which increases the likelihood of early marriage.27 An increase in age at first marriages has been documented over the past several decades.12 However, there is a paucity of information on whether changes accompany rural women. In Ethiopia, little is known about child marriage among rural women.\n\nTherefore, this research aims to investigate the prevalence of child marriage and its determinants among rural women of reproductive-age. This study has implications for policymakers in designing policies targeting rural girls by engaging local institutions in the study area, such as ‘Haadha siiqee’, an organization dedicated to defending women’s rights, the ‘Gadaa’, a governance organization that formulates and implements laws, and religious institutions to work against child marriage.\n\n\nMethods\n\nStudy setting: This study was conducted in the West Guji zone of southern Oromia. The zone was located 470 kilometers south of Ethiopia’s capital, Addis Ababa. The zone has three climatic zones: 37.8% lowlands (desert), 54.2% mid-highlands (Wayne degas), and 8% highlands (Degas). The zone is situated between 500 and 2200 m above sea level. The climatic conditions of the zone are relatively hot, and the annual average rainfall varies between 500 and 1200 ml. The zone has 10 administrative districts (9 rural districts and 1 urban district) and 196 kebeles (the lower-level administrative unit). The zone is bordered to the west and north by the southern nation, nationalities, and peoples region; to the east by the East Guji zone; and south by the Borana zone.\n\nGuji society is an Oromo ethnic group that preserves and practices Oromo traditional institutions such as the Gada system (indigenous governance system) which formulates and implements law. Another is the siinqee institution, which aims to protect women’s rights. Guji Oromo practiced arranged marriages (parents decided on marriage) rather than love marriages.28\n\nThe West Guji Zone Administration Office’s 2023 report that there were approximately 2.5 million residents in the zone, 50.4% of whom were men and 49.6% of whom were women. There are 303,636 women of reproductive age living in rural districts.\n\nStudy period: This study was carried out from April 1 to May 5, 2024.\n\nStudy design: A community-based cross-sectional study design was applied in this study.\n\nSource population: The source population for this study included all women of reproductive age (15-49 years) living in the rural districts of the West Guji zone.\n\nStudy population: The study population for this study include randomly selected women of reproductive age (15-49 years) living in selected Kebeles of the West Guji zone more than six months and who were available in their residential home during the study period from April 1 to May 5, 2024.\n\nInclusion criteria: Women of reproductive-age who were married and lived in selected Kebele for more than six months were included in the study.\n\nExclusion criteria: Women who were sick, had mental or hearing impairments, were in cohabiting relationships, and who did not stay for more than six months in selected Kebele were excluded.\n\nA single population proportion formula was used to determine the sample size for this study with the assumptions of Zα/2 = 1.96, 95% confidence level, 5% margin of error, 69.9% proportion of child marriage from the previous study,29 and design effect = 2, By adding a nonresponse rate contingency of 10%, the final sample size for this study was 711.\n\nA multistage sampling technique was adapted from earlier published studies20,30 and applied to select participants for this study. Out of the 9 rural districts, 4 districts were selected randomly. From the 96 kebeles found in the selected districts, 37 kebeles were selected based on proportion to size. After households (HHs) with eligible women were identified, a sampling frame was prepared for each selected kebele. Finally, the random sampling technique (computer-generated table of random number) was implemented to select households with eligible participants. In the case of more than one eligible woman of reproductive age in a single household, a lottery method was applied. By this method, 250 HHs with eligible women were selected in Bule Hora districts, 96 from Duda Dawa, 192 HHs in Kercha, and 173 HHs in Abaya Districts. This resulted in a total of 711 respondents selected from the households.\n\nDependent variable: In this study, child marriage is based on self-reported age during marriage. Women who get married before turning 18 are seen as experiencing child marriage.\n\nThe independent variables were sociodemographic factors such as age, marital status, education level, religion, occupation, family size, and family economic status. Service-related factors include the accessibility of media; the availability of girl’s supporting agencies, legal punishments against offenders of early marriage, and the availability of job opportunities for girls. Individual-related attributes, such as living arrangement, perceived marital age, and awareness of legal age, and context-related factors, such as criteria girl’s reached for marriage, custom of girls’ marriage at an early age, stigma associated with girls’ age, honor for girls and parents related to girls’ virginity, insecurity in the surroundings, conflict within the family, and marriage decision making are included.\n\nChild marriage: Child marriage is any marriage that takes place before the girl reaches the age of eighteen and for which she is not prepared for marriage and childbirth.20\n\nWealth index: The principal component analysis method was used to generate the wealth index. By factor loadings, three components were extracted. Each home was divided into three categories according to its score (low, medium, and high), which represented poor, medium, and rich households, respectively.\n\nThe data collection instrument was adapted after the relevant literature was reviewed.14,20,31 The tools were pretested and administered via face-to-face interview techniques. The questionnaires cover the sociodemographic and economic characteristics of the participant’s parent; the sociodemographic attributes of individual participants and predictors of marital age. The tools’ were prepared in English and reviewed by two language experts. The questionnaires translated into Afan Oromo, the official working language of the Oromia region, and then translated them back to English for consistency. A statistical analysis of the tools’ reliability revealed that their internal consistency Cronbach’s alpha score of 0.76 (76%) fell within an acceptable range. Tools were pretested in 5% (36 married women) of the study participants who lived in similar settings outside of the study area in the Uraga district of the East Guji zone, and on the basis of the findings, amendments were made. Ethical approval was obtained from the Bule Hora University Institute of Health Ethical Review Committee before the commencement of the study on 14 February 2024, reference number (Ref.no. BHU-IOH 02-012). Twenty health extension workers participated in the data collection. A total of ten supervisors supervised the data collection processes. The study assistants were trained for two days on the study instruments, and data collection procedures, including the relevance of the study, objective of the study, confidentiality of the collected data, and informed consent. The data collectors work under the close supervision of the supervisors.\n\nBefore the data were entered into Epi-Data version 4.4.3.1, all the data were cleaned, coded, and verified for completeness. The data were subsequently exported to the Statistical Package for Social Science (SPSS) version 25 for analysis. Both descriptive and inferential statistics were applied in this study. Descriptive statistics, frequencies, percentages, and means were calculated and are presented in the table.\n\nBinary and multivariable logistic regression models were used to identify determinants of child marriage. For bivariate analysis, variables that had a significant association at p <0.2 were selected for multivariable logistic regressions to determine the determinants of child marriage. The Hosmer-Lemeshow (HL) and Omnibus tests were used to assess the model’s fitness for the data, and the results revealed that the model fit the data well. A multicollinearity test was carried out to assess the correlation between independent variables. An adjusted odd ratio (AOR) with a 95% confidence interval (CI) was used to quantify the strength of the associations between the determinant factors and a response variable, and a p-value < 0.05 was taken to declare statistical significance.\n\n\nResults\n\nIn this study, 711 women were interviewed and the response rate was 100%. The mean marital age of the surveyed women was 17.5 ± (2.456 SD), and the median was 18 ± (3 IQR). The minimum and maximum ages at first marriage were 13 and 25 years, respectively. In terms of the respondents’ marital status, the majority of the women 682 (95.9%) were in a union, whereas a few of them 20 (2.8%) divorced. With respect to the participants’ level of education, 333 (46.8%) had a primary level of education, and only 37(4.9%) had attained a higher level of education, college education or above. The majority of the participants’ parents 464 (65.3%) had a large family size ≥7, and slightly more than half 369 (51.9%) of the study participants had a medium family size of 4-6 members. In terms of family wealth, one-third of the participants’ parents were in the poor wealth category (Table 1).\n\nAmong the interviewed women, nearly half 353 [49.6% (95% CI: 0.472-0.524)] had an age at first marriage less than 18 years (Figure 1).\n\nThe majority of the respondents 548 (77.1%) had followed media and of those who had access to media, two-thirds listened radio. A remarkable number of study participants 567 (79.7%) reported the absence of girls supporting agencies in their vicinity. More than half of them 423 (59.5%) reported a lack of legal punishment against perpetrators of early marriage. The majority of surveyed women 625 (87.9%) stated a lack of job opportunities in their locality for females (Table 2).\n\nA significant number of the respondents 638 (89.7%) believed that sexual intercourse before marriage was incorrect. Similarly, more than half of the participants 365 (51.3%) mentioned that sexual intercourse before marriage led to a girls’ marriage at an early age. Two-thirds 514 (72.3%) of the interviewed women lived with their parents before marriage, and 585 (82.3%) of them perceived the correct age of marriage as greater than or equal to 18 years. Similarly, 586 (82.4) respondents were aware of the legal age of marriage (Table 3).\n\nAmong the surveyed women, 591 (83.1%) reported the appearance of signs of puberty (breast enlargement, occurrence of menstruation) which is considered a criterion for a girl reaching marriage, and 469 (66%) women confirmed the custom of a girls’ marriage, age less than 18 years in their vicinity. The main reason for a girls’ marriage at a young age was to avoid premarital sexual practices and protect her virginity. The majority of women 664 (93.4%) reported that there was fear related to girls’ age, and the main reason for this fear was that they may miss the chance of marriage, family reputation, and stigma associated with girls’ age becoming older. A total of 632 (88.9%) and 591(83.1%) interviewed women reported that there is honor related to girls’ virginity for girls as well as for girls’ parents (Table 4).\n\nA bivariable logistic regression analysis was carried out to select variables for multivariable logistic regression, and 11 variables were significant at p < 0.2. These variables are the parent’s marital status, religion, fathers’ level of education, mothers’ education, the respondents’ level of education, exposure to media, live with before marriage, awareness of the legal age of marriage, marriage decision making, conflict within the family, and parents’ wealth status.\n\nIn the multivariable logistic regression, seven variables were significant at p < 0.05 religion, fathers’ level of education, exposure to media, live with before marriage, awareness of the legal age of marriage, marriage decision making, and parents’ wealth status.\n\nMuslim and Protestant followers were 2 times more likely to practice child marriage than Orthodox followers (AOR=2.104, 95% CI =1.176-3.764) and (AOR=1.877 95% CI=1.126-3.127). The participants whose fathers had no formal education were 2.6 times (AOR=2.633, 95% CI=1.135-6.109) more likely to marry before 18 years than those whose fathers had secondary education or above. Similarly, those fathers who attended the primary level were 3 times (AOR=3.326, 95% CI=1.421-7.787) more likely to practice child marriage than their counterparts. The odd of child marriage were 1.6 times (AOR=1.56, 95% CI=1.033-2.356) higher among the participants who had not been exposed to media than those who had been exposed to media. The participants, who lived with their relatives were 1.6 times (AOR=1.592, 95% CI=1.012-2.504) more likely to marry below 18 years than those who lived with their parents. Participants who were not aware of the legal age of marriage were 2.5 times (AOR=2.528, 95% CI=1.593-4.010) more likely married before 18 years than those who aware of the legal age of marriage. Participants who made marriage decisions by themselves were 33.4% (AOR=.666, 95% CI=.463-.959) less likely to marry below the age of 18 years than those whose marriage was decided by others. The participants whose parents were in the poor wealth category were 4.5 times (AOR=4.464, 95% CI=2.795-7.129) more likely to marry below the age of 18 than those whose parents were in the rich wealth category. Similarly, participants whose parents were in the middle wealth category were 2 times (AOR=2.040, 95% CI=1.318-3.156) more likely to marry before the age of 18 than their counterparts (Table 5).\n\n\nDiscussion\n\nThis study aims to identify the determinants of child marriage among women of reproductive age in the West Guji zone, southern Ethiopia. The results of this study demonstrated the mean age of first marriage, prevalence, and the determinants of child marriage. In this study, the mean and median ages at first union were 17.5 and 18 years, respectively. This means that almost half of the surveyed women were married before 18 years of age. In the study area, the onset of secondary sexual characteristics (occurrence of menses and breast enlargement) was considered as the criterion that the girls met for marriage. In addition, to avoid premarital affairs and protect girls’ virginity up to marriage, early marriage was encouraged by parents. These results are in line with those of previous studies carried out in Ethiopia, where the mean and median ages of the first union were 17.2 and 17.5,13 respectively,and in India, the median age of the first marriage was 18.2 years.32\n\nHowever, there was a slight improvement in the mean age of the first union compared with another study conducted in Ethiopia, which reported that the mean age of first marriage was 14.8 years.29 The observed discrepancy is perhaps due to study time, differences in the study population, sample size, and the commitment of the government to eliminate violence against women including early marriage. This implies that more effort is needed to scale up the age at first marriage and achieve the goal outlined in the national reproductive health policy, no gender-based violence, including early marriage by 2025,25 and the SDG 5.3 target.24\n\nThe present study revealed that the prevalence of child marriage among rural women was 49.6%. This finding is lower than previous studies conducted in Ethiopia the magnitude of child marriage ranges from 62.8% to 73%.29,31,33 The difference might be due to population size. The sample size of the former studies was larger. Furthermore, improvement in perceived age of marriage and awareness of legal marital age could contribute to the differences. However, the result was higher than the studies done in Eastern Ethiopia, Harari region (33.7%),20 central region of Eritrea (42%),15 Egypt (13.22%),34 and Indonesia (12.53%).35 The discrepancy might be due to differences in the study population. Both rural and urban women participated in the previous studies. The study results revealed that there was fear associated with girls’ age, and the reasons for this fear were may face difficulty to marry and age-related stigma. This finding is supported by a study conducted in the Harari region, in eastern Ethiopia.20 This could be because early marriage is a widely accepted and practiced custom in Ethiopia.\n\nReligion was one of the determinants of child marriages. The participants who follow Muslim were 2 times more likely to practice child marriage than Orthodox Christianity followers. This result is in agreement with a study carried out in Eastern Ethiopia.20 This is because religion is the cultural component that encourages early marriage as a means of preventing extramarital sex. Furthermore, Muslims believe that the union of Mohammed and Aisha is the cause of the practices of child marriage. Similarly, family wealth status was a significant predictor of child marriage. The participants whose parents were in the poor wealth category were 4.5 times more likely to marry below the age of 18 than those whose parents were in the rich wealth category. Similarly, participants whose parents were in the middle wealth category were 2 times more likely to marry before the age of 18 than their counterparts. This finding is in line with previous studies8,30,31 showing parents’ economic status is a potential determinant of child marriage in developing countries. Marriage at an early age is motivated by challenging economic conditions and families pressure their daughters to get married at an early ages for financial relief.36 Another piece of evidence suggests that poverty is closely associated with marital age. Early marriage is viewed by parents as a way to lessen the financial strain of raising and educating daughters.37 This has the implications for improving the living standards of girls’ families and increasing job opportunities for females to increase their age at first marriage.\n\nDespite the legal age of marriage being 18 years old in Ethiopia,25 lack of awareness of legal age marriage was risk factor of child marriage. Participants who were not aware of the legal age of marriage were 2.5 times more likely married before 18 years than those who aware of the legal age of marriage. The finding in line with report from Harari region that not know legal age marriage 4.49 time more likely married age below 18 years.20\n\nThe participants whose fathers had no formal education were 2.6 times more likely to marry before 18 years than those whose fathers had secondary education or above. Similarly, those fathers who attended the primary level were 3 times more likely to practice child marriage than their counterparts. This result supported by study conducted in the Amhara region, where the fathers’ education status was significantly associated with early marriage.30 The parents’ level of education has an influence on girls’ age at first marriage.22,38 This is because educated parents are aware of the negative consequences of marriage at an early age on the prospects of women’s lives.\n\nParticipants who made marriage decisions by themselves were 33.4% less likely to marry below the age of 18 years than those whose marriage was decided by others. This finding contradicts a cross-sectional study carried out in the central region of Eritrea, where the odds of early marriage were four times higher for women who had made marital decisions on their own.15 The difference might be due to sociocultural and population size. The population size in the current study is larger than that in previous study. This finding is supported by earlier studies conducted in Ethiopia20,31,39 showing that marriage decisions by parents are significantly associated with early marriage. In Ethiopia, parents have a major influence on marriage decisions.40\n\nThe large sample size in this study enables generalization to the target population, and face-to-face interviews conducted by native speakers of Afan Omomo can facilitate dialogue and ensure accurate data collection. However, there are certain drawbacks. First, the cross-sectional study design made it impossible to determine a cause-and-effect relationship between the predictor variables and the outcome. Second, the age at first marriage was asked retrospectively perhaps the possibility of recall bias.\n\n\nConclusion\n\nIn this study, nearly one in every two women were married before turning 18 years old and the mean age at first marriage was 17.5 ± (2.456 SD). The key determinant factors of child marriage in the study area marriage include religion, fathers’ level of education, exposure to media, living arrangements; awareness of the legal marital age, marriage decision making, and parents’ wealth status. The intervention strategies focus on these factors in order to rise the age at first marriage above 18 years, which can either directly or indirectly improve mother’s or children’s well-being. Improving family income, encouraging female participation in education, increasing awareness on the legal age of marriage, and increasing girls’ autonomy in marital decisions are essential to curve child marriage among rural women in the West Guji Zone. Moreover, the involvement of girl’s families, local elders, and religious leaders is vital to prevent the practice of child marriage in the study area.\n\nThis study involved human participants and complied with all relevant rules and regulations of the Helsinki Declaration of Medical Research Ethics.41 The Bule Hora University Institute of Health Ethical Review Committee granted ethical approval before the start of the study (Ref.no. BHU-IOH 02-012). Before signing the written informed consent form, all research participants were well-informed about the study’s goals, advantages, and significance. A permission letter was provided to the West Guji Zone administration office, selected districts, and Kebeles. The participants were informed of their freedom to withdraw from the study at any time, and their anonymity was protected by providing pseudonyms. The collected data were stored in electronic files with a code and password to ensure confidentiality.\n\n\nAuthor contributions\n\nSG - Conceptualization, methodology, Data curation, Formal analysis, Software, Writing-Original draft, DW- Investigation, editing and reviewing, and supervision., MD - Methodology, Visualization and Validation.",
"appendix": "Data availability\n\nFigshare: Determinants of child marriage among rural women in the West Guji Zone, Southern Ethiopia, 2024: a community-based cross-sectional study, DOI: https://doi.org/10.6084/m9.figshare.27188259.v2. 42\n\nThis project contains the following underlying data:\n\n• data2.sav\n\nFigshare: Determinants of child marriage among rural women in the West Guji Zone, Southern Ethiopia, 2024: a community-based cross-sectional study, DOI: https://doi.org/10.6084/m9.figshare.27188259.v2. 42\n\nThis project contains the following:\n\n• Questionnaire\n\nFigshare: Determinants of child marriage among rural women in the West Guji Zone, Southern Ethiopia, 2024: a community-based cross-sectional study, DOI: https://doi.org/10.6084/m9.figshare.27188259.v2. 42\n\nThis project contains the following:\n\n• STROBE CHECK\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgement\n\nAll the authors expressed their gratitude to the study participants and data collectors.\n\n\nReferences\n\nNour NM: Health consequences of child marriage in Africa. 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African study monographs. 2009; 30(1): 15–36.\n\nMulleta AD, Muda K: Deciphering meanings embedded in the cultural ornaments of Guji Oromo women of Southern Ethiopia. Heliyon. 2021; 7(4): e06774. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGetu M, Emirie G, Habtamu K: The prevalence and drivers of early marriage across three generations in three districts from Amhara, Oromia and Southern Nations, Nationalities and Peoples regions of Ethiopia. Ethiopian Journal of the Social Sciences and Humanities. 2021; 17(2): 91–112.\n\nBezie M, Addisu D: Determinants of early marriage among married women in Injibara town, north West Ethiopia: community-based cross-sectional study. BMC Womens Health. 2019; 19: 1–6. Publisher Full Text\n\nAychiluhm SB, Tesema AK, Tadesse AW: Early marriage and its determinants among married reproductive age group women in Amhara Regional State, Ethiopia: a multilevel analysis. Biomed. Res. Int. 2021; 2021(1): 1969721.\n\nPandya YP, Bhanderi DJ: An epidemiological study of child marriages in a rural community of Gujarat. Indian J. Community Med. 2015; 40(4): 246–251. PubMed Abstract | Publisher Full Text\n\nTessema ZT: Spatial distribution and associated factors’ of early marriage among reproductive age women in Ethiopia: a secondary data analysis of Ethiopian Demographic and Health Survey 2016. BMC Womens Health. 2020; 20(1): 268. PubMed Abstract | Publisher Full Text | Free Full Text\n\nElnakib S, Elsallab M, Wanis MA, et al.: Understanding the impacts of child marriage on the health and well-being of adolescent girls and young women residing in urban areas in Egypt. Reprod. Health. 2022; 19(1): 8. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKuswanto H, Oktaviana PP, Efendi F, et al.: Prevalence of and factors associated with female child marriage in Indonesia. PLoS One. 2024; 19(7): e0305821. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKok MC, Kakal T, Kassegne AB, et al.: Drivers of child marriage in specific settings of Ethiopia, Indonesia, Kenya, Malawi, Mozambique and Zambia–findings from the Yes I Do! baseline study. BMC Public Health. 2023; 23(1): 794. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPsaki SR, Melnikas AJ, Haque E, et al.: What are the drivers of child marriage? A conceptual framework to guide policies and programs. J. Adolesc. Health. 2021; 69(6): S13–S22. Publisher Full Text\n\nTan Q: Parents’ influence on children’s marital decision case study: China. Cogent Social Sciences. 2023; 9(1): 2179433. Publisher Full Text\n\nAlem AZ, Yeshaw Y, Kebede SA, et al.: Spatial distribution and determinants of early marriage among married women in ethiopia: a spatial and multilevel analysis. BMC Womens Health. 2020; 20: 1–13. Publisher Full Text\n\nAlemu B: Early marriage in Ethiopia: causes and health consequences. Exchange on HIV and AIDS, Sexuality and Gender. 2008; 1: 4–6.\n\nAssociation WM: World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013; 310(20): 2191–2194. Publisher Full Text\n\nGelchu SW, Dessalegn, Dheresa M: Determinants of child marriage among rural women in the West Guji Zone, Southern Ethiopia, 2024: a community-based cross-sectional study. Dataset. figshare. 2024; 2024."
}
|
[
{
"id": "344911",
"date": "28 Dec 2024",
"name": "John Boulard Forkuor",
"expertise": [
"Reviewer Expertise Social Protection and Social Welfare"
],
"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. The authors address a topic that is of international and African concern. A topic that has socio-cultural and legal determinants and implications. I appreciate the attempt to tease out the key determinants as this has potential implications for intervention/re-dress\nFundamental Question to Authors. Can a perception study be used to establish determinants of a phenomenon like child marriage? When you ask people about their perception regarding pre-marital sex (for instance) as you do in this study, does that allow you to say anything about pre-marital sex determining child marriage? This particular limitation seems to be acknowledged by the authors in the section labeled “Strengths and limitations of the study”. If this limitation is fundamental to the study and acknowledged by the authors, then the research cannot have “determinants of child marriage” as part of the topic. I suggest the authors take a look at this again.\nIntroduction. In the introduction, the authors situate their study by claiming that there has been little research on child marriage in rural Ethiopia. I refer the authors to the following references (Erulkar and Muthengi, 2009; Alem et al., 2020; Erulkar, 2022; Gebeyehu et al., 2023). Please refer to suggested readings below for the full list of references. Some of these are systematic reviews and meta-analyses of child marriage in Ethiopia. How do the authors situate their research within this broad literature? Suppose the authors feel that their study is significantly different. In that case, I recommend that they include a brief sentence acknowledging these studies and indicating how the present study is different from what exists.\nMethods. While the authors provide a brief geographical description of the setting, they do not provide enough socio-cultural description of the setting that will help readers understand the relevance of the setting to this particular research. I acknowledge the short write-up on the local traditional institutions of governance. Can this be firmed up? Again, since child marriage occurs at the intersections of social, cultural, and legal systems, I would suggest that the authors spend more time explaining the socio-cultural realities of the context. This will be important in helping readers not only appreciate the choice of the setting but also in interpreting the research in context. Regarding the inclusion and exclusion criteria, I find it curious that parents and community leaders (both of whom are key cultural stakeholders and contribute to determining child marriage) were not targeted. Do the authors have a specific reason for this? If the authors wanted to prioritize the voice of women who have experienced the phenomenon over all other groups, they should indicate that early on and provide a clear justification as to why this focus is relevant to their study. As it stands, it appears the authors are discussing determinants of child marriage (a phenomenon that is also socio-cultural) without engaging the socio-cultural stakeholders who are active in determining the incidence of child marriage. My other concern with the study population has to do with the exclusion of persons with hearing impairment. In the spirit of inclusion, the authors need to clarify why women with hearing impairment were not included. This is important to prevent the perception or appearance of the authors devaluing the voice and experience of women with hearing impairment. The contention here is that having a hearing impairment does not in itself invalidate a woman’s experience of early marriage, neither does it invalidate her perception of same. The authors need to clarify this particular exclusion for readers. Regarding sampling, the authors make the following statement: “after households with eligible women were identified”. I suggest that the authors provide a better explanation of how households with eligible women were identified in this particular study. The independent variables are quite confusing for me. I assume from the work that these are variables determining child marriage. So, when the authors indicate “age” for instance, whose age is determining the child marriage here? Again, for marital status, are the authors looking at the marital status of parents or the child bride herself as a determinant for child marriage? I am unclear as to how these two could be considered independent variables that determine the occurrence of child marriage. This is because, age is already a factor in the operationalization of child marriage, the same for marital status. I have similar concerns about religion and occupation. It will be good for the authors to explain how these are considered independent variables for this study.\nResults, discussion and conclusion. The authors indicate in the final paragraph of their introduction that they want their research to have implications for policy and intervention. As a result, it is important that in the conclusion they rely on their findings to indicate the key points of policy and intervention and how this will be different and more relevant than existing policies and interventions at reducing the incidence of child marriage. Given the results, what are the key points of intervention within such resource-constrained contexts? Answering this question will improve the research. In the results, the authors indicate the mean age of first marriage. It would help if they added the frequencies and percentages first. For instance, it will help to know the proportion of respondents who were married before 18 compared to those who married above 18. This basic comparison allows us to understand your claims about the likelihood of marriage in the subsequent sections. For instance, if 100% of respondents were married before 18, what will be the essence of the analysis that seems to relate the likelihood of early marriage to some other socio-demographic characteristic? The variable religion, does it assess the religion of the participant? Or does it assess the religion of their father? Or Mother? This should be clarified. In the section labeled ‘Factors associated with child marriage’, you make the following statement: “…fathers who attended the primary level were 3 times more likely to practice child marriage than their counterparts”. Which counterparts are the authors referring to? Are they referring to counterparts who had secondary education or counterparts who had no primary education?\nAs this is a quantitative study that seeks to establish relationships, these clarifications will help readers understand the measures and the relationships that the authors establish among the variables.\nSuggested Readings Erulkar AS, et al., 2009 (Ref 1)\nErulkar, A. (2022) Ref 2\nAlem AZ, et al., 2020 (Ref 3)\nGebeyehu NA, et al., 2023 (Ref 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? 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/13-1322
|
https://f1000research.com/articles/13-1320/v1
|
05 Nov 24
|
{
"type": "Research Article",
"title": "A global overview of the use of cone beam computed tomography in dentistry: a bibliometric review focusing on paediatric patients",
"authors": [
"Danielle Cristina Alves Rigo",
"Aurélio de Oliveira Rocha",
"Lucas Menezes dos Anjos",
"Pablo Silveira Santos",
"Isabela Ramos",
"Michely Cristina Goebel",
"Julia Maldonado Garcia",
"Gabriela Beatriz Rigo Wietzkoski",
"Carla Miranda Santana",
"Mariane Cardoso",
"Aurélio de Oliveira Rocha",
"Lucas Menezes dos Anjos",
"Pablo Silveira Santos",
"Isabela Ramos",
"Michely Cristina Goebel",
"Julia Maldonado Garcia",
"Gabriela Beatriz Rigo Wietzkoski",
"Carla Miranda Santana",
"Mariane Cardoso"
],
"abstract": "Background Cone Beam Computed Tomography (CBCT) has improved diagnosis and treatment planning in paediatric dentistry, but no bibliometric studies have examined the research landscape. This study provides an overview of CBCT in paediatric dentistry.\n\nMethods A bibliometric review was conducted using articles from the Web of Science database up to February 2024. Conference papers and editorials were excluded. Data extracted included citation counts, publication dates, journals, impact factors, study designs, topics, geographical and institutional affiliations, authors, and keywords. Collaborative networks were visualised using VOSviewer, and Spearman’s correlation assessed the relationship between citation counts and other variables.\n\nResults The review analysed 517 articles, with the most cited receiving 557 citations. Publication dates ranged from 2005 to 2024, with a peak in 2023. Observational studies were the most common, particularly on maxillary expansion. The American Journal of Orthodontics and Dentofacial Orthopedics was the most cited journal, and the USA was a major contributor. Jacobs R authored the most articles (n=19), and the University of Alberta led in institutional output. Spearman’s correlation showed a weak positive correlation between citation count and journal impact factor (rho=0.272, p<0.001) and a strong negative correlation with publication year (rho=-0.762, p<0.001).\n\nConclusions This bibliometric review provides an overview of the use of CBCT in paediatric dentistry, particularly in maxillary expansion. The findings suggest that more specific imaging protocols may improve safety and clinical outcomes, and that further investigation of long-term outcomes may provide valuable insights.",
"keywords": [
"Cone-Beam Computed Tomography",
"CBCT",
"Paediatric",
"Dentistry",
"Bibliometric Analysis"
],
"content": "Introduction\n\nCone beam computed tomography (CBCT) represents a diagnostic imaging approach using x-radiation to reproduce a specific section of the human body in any of the three planes of space.1 In contrast to conventional radiographs, which project all the structures traversed by X-rays in a single plane, CBCT highlights structural relationships in depth, presenting images in “slices”.2 Unlike multi-slice computed tomography (MSCT), CBCT uses an X-ray source composed of a fixed low-energy anode, similar to those used in dental panoramic tomography.3 Despite having a lower incidence of radiation than MSCT, CBCT generates high-resolution images and minimizes the likelihood of metallic artefacts. In addition, it offers the ability to generate all two-dimensional images as required.4,5\n\nAlthough CBCT is a growing imaging technology with several dentomaxillofacial applications, its use in paediatric dental patients remains a sensitive point, mainly due to the radiation doses involved.6 Specific recommendations aimed at guiding the justified indication of the use of CBCT in paediatric dental patients were discussed as part of the European project DIMITRIA (Paediatric dentomaxillofacial imaging: an investigation into low-dose radiation-induced risks), which focused on optimizing the doses applied to children.7 Despite the need for a cautious approach, particularly for the investigation and appropriate treatment of orofacial and jawbone pathologies, as well as specific situations such as dental trauma, orofacial clefts and supernumerary teeth, the use of CBCT is justified.4 Given this scenario, the use of CBCT in paediatric dental patients has emerged as a crucial imaging exam to help professionals diagnose and prognosticate numerous oral conditions in children.5,8,9\n\nDespite the widespread use of CBCT in paediatric dental care, there is a lack of comprehensive bibliometric analyses that examine the trends, geographical distribution, and scientific collaborations in this area. Many studies have focused on the technical aspects and clinical applications of CBCT,1,3–5,7–9 but no studies have been found to date that have systematically mapped the research landscape to identify gaps in knowledge and areas that need further investigation. Furthermore, concerns about radiation exposure in children underscore the importance of establishing clearer protocols and guidelines for its safe application. Existing studies tend to concentrate on specific clinical outcomes, leaving a broader understanding of CBCT’s impact on paediatric dental care largely unexplored.\n\nBibliometric studies map existing concepts, indicating the main trends in scientific research and the main dental methods and tools used.10,11 These analyses allow researchers to identify patterns, assess influential indicators, recognise leading authors, evaluate prominent journals, and highlight countries with the most significant research output. Additionally, bibliometric analysis enables the visualisation of collaborative networks between researchers.12 Although bibliometric studies have been conducted in several fields of dentistry,13–16 no studies to date have specifically focused on the use of CBCT in paediatric dentistry. In light of this gap, the aim of this study was to conduct a bibliometric analysis to provide a comprehensive panorama on the scientific landscape of CBCT on paediatric dentistry and to guide future clinical and research developments.\n\n\nMethods\n\nThis study complies with the Guideline for Reporting Bibliometric Reviews of Biomedical Literature (BIBLIO)17 and follows a rigorous standard of data collection and analysis.17,18\n\nA literature review was conducted to identify studies using CBCT in paediatric dental patients. The search covered publications up to February 2024, with no restrictions on language or publication year. The bibliographic search was conducted in the Web of Science - Core Collection (WoSCC) database, using the following search strategy: [TS=(“Cone-Beam Computed Tomography” OR “Cone Beam Computed Tomography” OR CBCT OR “Computed Tomography, Cone-Beam” OR “Cone Beam Computed Tomography” OR “CT Scan, Cone-Beam” OR “CT Scan, Cone Beam” OR “CT Scans, Cone-Beam” OR “Cone-Beam CT Scan” OR “Cone-Beam CT Scans” OR “Scan, Cone-Beam CT” OR “Scans, Cone-Beam CT” OR “Tomography, Cone-Beam Computed” OR “Tomography, Cone Beam Computed” OR “CAT Scan, Cone-Beam” OR “CAT Scan, Cone Beam” OR “CAT Scans, Cone-Beam” OR “Cone-Beam CAT Scan” OR “Cone-Beam CAT Scans” OR “Scan, Cone-Beam CAT” OR “Scans, Cone-Beam CAT” OR “Cone-Beam Computer-Assisted Tomography” OR “Computer-Assisted Tomography, Cone-Beam” OR “Cone Beam Computer Assisted Tomography” OR “Tomography, Cone-Beam Computer-Assisted” OR “Cone-Beam Computerized Tomography” OR “Computerized Tomography, Cone-Beam” OR “Cone Beam Computerized Tomography” OR “Tomography, Cone-Beam Computerized” OR “Cone-Beam CT” OR “CT, Cone-Beam” OR “Cone Beam CT”) AND ((“Paediatric Dentistry” OR “Dentistry, Paediatric” OR “Paediatric Dentistry” OR “Dentistry, Paediatric”) OR (child* OR schoolchild* OR “school child*” OR adolescen* OR juvenil*) OR (“tooth, deciduous” OR “deciduous tooth” OR “deciduous teeth” OR “milk teeth” OR “milk tooth” OR “primary teeth” OR “primary tooth” OR “primary dentition”))]. Two researchers independently conducted the study selection process, and a third author was consulted in the event of disagreements. Studies were only included when all the reviewers reached a consensus. Studies that were not research articles (such as conferences or editorials) and did not use CBCT in paediatric dental patients were excluded.\n\nFor each article, data was collected such as number and density of citations (number of citations per year), year of publication, journal impact factor (JIF), study design, theme (main objective of the study), country and continent, institution (based on the corresponding author), authors and keywords. The study designs were categorized as systematic review, interventional, observational, case report or series, literature review and laboratory study. Considering the theme, the studies were grouped considering the central outcomes of each study. Themes that were reported in only one study were grouped under “other”.\n\nThe selected articles were entered into the VOS Viewer software (version 1.6.18) (https://www.vosviewer.com) to create visual representations that show collaboration between authors and keywords. Words associated with the most prominent foci indicate greater frequency, while words of the same color and linked together form networks, highlighting more intense collaboration between studies. The correlation between the number of citations, the year of publication and the journal’s impact factor was explored using SPSS for Windows statistical software (SPSS, version 24.0; IBM, Armonk USA Corp). The Kolmogorov-Smirnov test was used to verify the normality of the data distribution, and Spearman’s correlation test was used due to the non-normal distribution. As an alternative, Microsoft Office Excel can be used to carry out these statistical calculations (normality test and correlation), with the relevant database provided in the Data Availability section.19\n\n\nResults\n\nThe literature search identified a total of 1,147 records. After the selection process, 517 articles were included for bibliometric analysis. Of the articles not included, two were editorials, three were from conferences, and the remaining (n=625) were excluded because they did not address the objective of the study.19\n\nThe selected articles accumulated a total of 7,538 WoSCC citations. Of these, 896 were self-citations (11.53%). The average number of citations per year was 396.7. The most cited article on WoSCC was “Effective dose of dental CBCT-a meta-analysis of published data and additional data for nine CBCT units”, with 257 citations, published in Dentomaxillofacial Radiology.20 Spearman’s correlation revealed a weak positive correlation between the number of citations and the journal’s impact factor (rho=0,272; p<0.001) and a strong negative correlation between the number of citations and the year of publication (rho=-0.762; p<0.001).\n\nThe articles were published between 2005 and 2024, spanning 19 years. The earliest publications date back to 2005,7 while the most recent, up to February 2024, total two.21,22 The year with the highest number of publications was 2023, with 71 articles indicating a recent and significant interest in research related to this topic. The distribution of the number of publications over the years can be seen in Figure 1.\n\nThe most frequent journals that published articles on the use of CBCT in paediatric dental patients are shown in Table 1. The American Journal of Orthodontics and Dentofacial Orthopedics (n=69) was the most prominent journal, followed by Angle Orthodontist (n=30) and Dentomaxillofacial Radiology (n=23). According to Journal Citation Reports, the journals with the highest IF in 2022 linked to this study were the Journal of Dental Research (IF 7.7; 1 occurrence), European Radiology (IF 5.9; 2 occurrences) and the International Endodontic Journal (IF 5.0; 1 occurrence), all contributing one article each.\n\nMost of the articles were observational studies (n=352), followed by laboratory studies (n=54), case reports or series (n=39), interventional studies (n=41), literature reviews (n=20) and systematic reviews (n=11). About the themes of the selected studies, the majority of studies used CBCT to plan and assess maxillary expansion (n=87), followed by aid in endodontic diagnosis and treatment (n=39) and to aid in the diagnosis and treatment of cleft lip and/or palate (n=38). Table 2 lists the different themes with their respective study designs and the year in which the articles were published.\n\nA total of 52 countries contributed to the articles related to the use of CBCT in paediatric dental patients. Considering the number of publications per country, the most prevalent were the USA (n=64), China (n=63), Turkey (n=55), South Korea (n=37) and Brazil (n=36). Among the continents with the most articles, Asia stands out (n=232), followed by Europe (n=144) and North America (n=80). The worldwide distribution of publications can be seen in Figure 2.\n\nThrough the data contained in the corresponding authors of the selected studies, 301 different institutions were identified. The University of Alberta (Canada) was the institution with the largest number of documents (n=11). Table 3 shows the top 10 institutions.\n\nThe authors with the highest number of articles were Jacobs R (n=19), Lagravere MO (n=16) and Sekerci AE (n=14). Figure 3 highlights the collaboration and the main groups of authors, while Table 4 shows the 10 authors with the highest number of publications.\n\nA total of 1,841 keywords were identified. The most prevalent was “children” (n=118), followed by “CBCT” (n=85) and “cone-beam computed tomography” (n=83). Figure 4 shows the most prevalent keywords (5 or more occurrences) and the collaborative relationships between them.\n\n\nDiscussion\n\nIn paediatric dental patients, CBCT plays a crucial role in diagnosing oral conditions such as dental fractures and bone lesions.4 In addition, it serves as an essential tool in planning procedures such as maxillary expansion and correction of nasopalatine clefts.23 This study identified the main applications of CBCT in paediatric dental patients, analysed the profile of publications related to this topic and discussed possible future trends for research in this field. The results revealed that the emphasis is predominantly on observational studies, concentrating on the diagnosis and planning of patients with maxillary atresia who require expansion procedures.\n\nThe most cited article, published in 2015, is a systematic review that aimed to analyse dose measurement and estimate the effective dose for performing CBCT with dental applications.20 In this study, the authors indicated that the effective dose for performing CBCT in children ranges from 13 to 769 μSv for large or medium fields of view and 7 to 521 μSv for small FOV fields of view. The abundance of citations in this study highlights not only the importance of using CBCT in dental applications but also underscores the crucial need for accurate measurement of radiation exposure, especially in paediatric dental patients.\n\nA cohort study carried out in the UK, involving approximately 175,000 individuals who were children when exposed to CT scans of the head, revealed that cumulative doses of around 50 mGy almost tripled the risk of leukaemia, while doses of around 60 mGy almost tripled the risk of brain cancer.24 Similar results were observed in an Australian cohort of 10.9 million people aged between 0 and 19, showing a 24% increase in the incidence of cancers, including brain cancers and leukaemia, after exposure to CT scans. This incidence was correlated with increased dose and young age at the time of exposure.25 Although the risk of dentomaxillofacial imaging using CBCT is small for an individual, when multiplied by the large population of patients exposed to diagnostic imaging, the risk of radiation becomes a significant public health problem, especially in children and adolescents.20\n\nWhen comparing this study with other bibliometric studies,16,17,26 a significant number of self-citations can be observed. Although this practice is not widely accepted in the scientific community, it can be considered a natural consequence. Authors and research groups dedicated to a specific topic may find the need to self-cite their own work in order to contribute to the ongoing development of this area.27\n\nThe oldest article, published in 2008, proposes the use of reference points for cephalometric analysis using three-dimensional (3D) CBCT reconstruction with orthodontic indications.28 In this study, CBCT scans of 10 adolescents were used, and the authors indicated that the reference point with the highest intra-reliability was located between the two spinous foramina. With the indication of this cephalometric point, the authors proposed a tool that could be used as a reference for orthodontists when analysing 3D images since the use of this type of image, as it is an anatomically true representation (1:1 size), from which the sections can be displayed from any angle in any part of the skull and provided digitally on paper or film, can provide useful information for identifying teeth and other structures for diagnostic and descriptive purposes.\n\nSince 2005, publications investigating or using CBCT in children and adolescents have shown an upward trend over the years. A significant increase in the years 2021, 2022 and 2023 stands out, once again highlighting the relevance of this imaging exam in paediatric dental patients. This trend suggests not only recognition of the clinical importance of CBCT but also reinforces confidence in its safety when applied to this specific age group.\n\nThe American Journal of Orthodontics and Dentofacial Orthopedics was the journal with the highest number of published articles and, therefore, the highest number of citations. However, it was well below the JIF, occupying only seventh position. The JIF is the annual average of citations of the articles published by the journal over the last two years.29 It is noteworthy that, despite the International Journal of Paediatric Dentistry and the European Journal of Paediatric Dentistry being the paediatric dentistry journals with the highest JIF, the number of studies published on CBCT (cone beam computed tomography) in these journals remains considerably lower than in the most frequently cited dental journals.\n\nThe choice of study design plays an important role in the quality and reliability of research findings. In paediatric dentistry, the use of CBCT has been investigated using a variety of study designs, including observational studies, clinical trials, case reports and systematic reviews. Selecting the appropriate study design helps to address specific research questions, such as the applicability of CBCT from clinical diagnosis and treatment planning to the assessment of long-term outcomes.\n\nThe predominance of observational studies in this review aligns with previous bibliometric analyses in dental research, where observational designs are often favoured for their ability to collect data in real-world settings.11,12 While observational studies provide valuable information on trends and associations in clinical practice, their limitations, such as the inability to establish causal relationships and control for confounding variables, should be acknowledged.18 Previous studies, including those on CBCT applications in orthodontics and endodontics, have also highlighted the usefulness of such designs in documenting treatment outcomes and identifying practical applications.3,10\n\nHowever, the low proportion of randomised controlled trials (less than 1%, with only five studies) identified in this global review may be attributed to the ethical and practical challenges of conducting trials involving ionising radiation in paediatric populations. Given the risks associated with radiation exposure, particularly the long-term risks of cancer, RCTs in this area are difficult to justify.24 In contrast, controlled studies would offer a more rigorous assessment of outcomes and potential risks, particularly regarding radiation exposure in children.6 Instead, observational studies are more commonly employed, as they allow for the exploration of CBCT’s evolving role in treatments without the need for unnecessary radiation exposure.16,30\n\nMost of the studies included in this analysis used CBCT to plan and assess maxillary expansion, highlighting the importance of this technology in complex orthodontic diagnoses. CBCT is widely used to evaluate bone morphology and tissue response to rapid maxillary expansion (RME), particularly in children with maxillary atresia. Studies such as Fastuca et al. (2015)30 demonstrate that CBCT provides detailed insight into airway changes following RME, allowing for accurate evaluation of skeletal and dentoalveolar modifications. Additionally, CBCT has proven essential for three-dimensional documentation of bone and dental movement, offering precision in post-treatment follow-up, which facilitates planning for additional interventions. However, the potential for CBCT to reduce radiation exposure in paediatric patients requires further exploration, particularly in optimising image acquisition protocols.\n\nAnother significant use of CBCT was in aiding endodontic diagnosis and treatment, with an increasing emphasis on its use to assess root canal volume and untouched areas after instrumentation, as discussed by Gogos et al. (2020).11 CBCT offers high-resolution images, enabling precise three-dimensional visualisation of anatomical structures such as roots and canals, which are often challenging to assess in conventional two-dimensional radiographs. This accuracy facilitates the diagnosis of hidden pathologies and improves the success of endodontic treatments. However, there is an opportunity to expand research on the long-term impact of CBCT on clinical success in endodontic treatments, as well as its application in guided endodontic techniques.\n\nCBCT was also widely used in the diagnosis and treatment of cleft lip and/or palate, where its ability to generate detailed three-dimensional images is indispensable for surgical planning. The clear visualisation of the palate and surrounding areas allows for accurate assessment of the cleft and associated bone structure. The CBCT has been widely used in preoperative planning and postoperative follow-up of these corrections, especially in paediatric patients. However, despite its widespread use, the challenge of minimising radiation exposure in children remains a priority, necessitating further studies focused on developing low-dose imaging protocols.16\n\nDifferent institutions carried out most of the studies. The University of Alberta in Canada emerged as the most important institution with the highest number of publications. This prominence can be attributed to the university’s robust research programmes in paediatric dental patients and its significant investment in imaging technologies. Ranked in the top 100 in the world and fourth in Canada,31 the University of Alberta has extensive resources and expertise that are likely to contribute to its high output in this area. In addition, the presence of specialised research centres and strong collaborative networks with other leading institutions may enhance its ability to produce influential research in CBCT and paediatric dental patients, which may explain the significant number of articles in this bibliometric analysis.\n\nJacobs R was the most prominent author, focusing his articles mainly on observational and laboratory studies. His focus is on the assessment of radiation dose during cone beam computed tomography (CBCT) scans. On the other hand, the second most prominent author is Lagravere MO, whose production covers observational and interventional studies, with a particular emphasis on maxillary expansion. These authors, although clustered in 2018, belong to different research groups without any collaboration. These two authors stand out as significant contributors to the field, each bringing valuable perspectives and knowledge to research related to CBCT and paediatric dental patients.\n\nThe findings of this bibliometric review have important clinical implications for professionals in the field of paediatric dental patients. The principal application of CBCT in maxillary expansion, as evidenced in this review, highlights its efficacy in the differential diagnosis and treatment planning of patients with complex maxillofacial conditions. For clinicians, an awareness of these trends can facilitate the identification of cases in which CBCT should be used to optimise patient outcomes. This encompasses cases that demand precise imaging for orthodontic assessments, surgical planning, or the evaluation of cleft lip and palate. Furthermore, the data suggests an increasing focus on reducing radiation exposure, which is vital for establishing safe practice protocols. Consequently, this review offers clinicians a detailed account of contemporary research trends, thereby facilitating the formulation of optimal practices and providing a foundation for evidence-based clinical decision-making.\n\nFurthermore, this study did not impose any restrictions regarding publication year, citations, or language, thereby enabling a comprehensive and inclusive analysis of all documents pertaining to CBCT in paediatric dental patients up to the date of the research. This appears to be the inaugural bibliometric review to address this topic in such a comprehensive manner.\n\nWhile this review offers a thorough examination of the use of CBCT in paediatric dental patients based on data from the Web of Science database, it is crucial to recognize certain limitations inherent in this approach. The decision to focus on a single database, excluding others such as Scopus or PubMed, might have restricted the breadth of the analysis. Consequently, some relevant studies published in other databases may not have been considered. This choice aligns with the methodology used in previous bibliometric reviews,15,17 and was made to maintain consistency with established research practices. Nonetheless, to achieve a more exhaustive understanding of the available literature and reduce the risk of overlooking significant findings, future research would benefit from adopting a more inclusive search strategy that encompasses multiple databases. This approach could help mitigate the potential for biases associated with the selection of a single data source.\n\n\nConclusions\n\nThis bibliometric review provided an overview of the current state and trends in research into the use of CBCT for dental purposes in children and adolescents. An important finding was the greater research interest in Asia and Europe. Although the oldest article was published 19 years ago, there has been substantial growth in this area in the last four years, with an emphasis on observational studies aimed at assessing maxillary expansion. It is important to note that most of these studies were published in the American Journal of Orthodontics and Dentofacial Orthopedics, with the United States and China being the most frequent origins of these contributions. This panorama reflects not only the significant advance in research involving CBCT in paediatric dental patients but also points to a geographic distribution that highlights interest and scientific production in this specific area.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nFigshare: Dataset Supporting the Bibliometric Review of Cone Beam Computed Tomography in Paediatric Dentistry. https://doi.org/10.6084/m9.figshare.27176001.v5. 19\n\nThe project contains the following extended data:\n\n• Bibliom_CBCT.xlsx and Data Files CBTC.sav (Raw bibliometric data extracted from the top-cited articles on Cone Beam Computed Tomography (CBCT), supporting the findings of the study),\n\n• Flow diagram-v1\n\nFigshare: BIBLIO checklist for ‘A global overview of the use of cone beam computed tomography in dentistry: a bibliometric review focusing on paediatric patients’. pdf. https://doi.org/10.6084/m9.figshare.27176001.v5. 19\n\nFigshare: Flow diagram of the selection process of the included studies. https://doi.org/10.6084/m9.figshare.27176001.v5. 19\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 Public domain dedication).\n\n\nReferences\n\nGaêta-Araujo H, Alzoubi T, Vasconcelos KF, et al.: Cone beam computed tomography in dentomaxillofacial radiology: a two-decade overview. Dentomaxillofac. Radiol. 2020; 49(8): 20200145. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFeldkamp LA, Davis LC, Kress JW: Practical cone-beam algorithm. J. Opt. Soc. Am. A-Opt. Image Sci. Vis. 1984; 1(6): 612–619. Publisher Full Text\n\nDe Vos W, Casselman J, Swennen GR: Cone-beam computerized tomography (CBCT) imaging of the oral and maxillofacial region: a systematic review of the literature. Int. J. Oral Maxillofac. Surg. 2009; 38(6): 609–625. PubMed Abstract | Publisher Full Text\n\nOenning AC, Jacobs R, Pauwels R, et al.: Cone-beam CT in paediatric dentistry: DIMITRA project position statement. Pediatr. Radiol. 2018; 48(3): 308–316. PubMed Abstract | Publisher Full Text\n\nSingh P, Saha S, Tripathi AM, et al.: Cone-beam Computed Tomographic Analysis of Deciduous Root Canals after Instrumentation with Different Filing Systems: An In Vitro Study. Int. J. Clin. Pediatr. Dent. 2022; 15(Suppl 1): S22–S29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWhite SC, Scarfe WC, Schulze RK, et al.: The Image Gently in Dentistry campaign: promotion of responsible use of maxillofacial radiology in dentistry for children. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2014; 118(3): 257–261. PubMed Abstract | Publisher Full Text\n\nOenning AC, Salmon B, Vasconcelos KF, et al.: DIMITRA paediatric skull phantoms: development of age-specific paediatric models for dentomaxillofacial radiology research. Dentomaxillofac. Radiol. 2018; 47(3): 20170285. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhardwaj SS, Alghamdi S, Almulhim B, et al.: CBCT in Paediatric Dentistry: Awareness and Knowledge of Its Correct Use in Saudi Arabia. Appl. Sci.-Basel. 2022; 12(1). Publisher Full Text\n\nSolano Mendoza P, Aceytuno Poch P, Solano Reina E, et al.: Skeletal, Dentoalveolar and Dental Changes after “Mini-Screw Assisted Rapid Palatal Expansion” Evaluated with Cone Beam Computed Tomography. J. Clin. Med. 2022; 11(16): 4652. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGogos C, Kodonas K, Fardi A, et al.: Top 100 cited systematic reviews and meta-analyses in dentistry. Acta Odontol. Scand. 2020; 78(2): 87–97. PubMed Abstract | Publisher Full Text\n\nRocha AO, Santos PS, Machado BA, et al.: The Top 100 Most-Cited Papers in Erosive Tooth Wear: A Bibliometric Analysis. Caries Res. 2022; 56(1): 29–35. PubMed Abstract | Publisher Full Text\n\nJayaratne YS, Zwahlen RA: The evolution of dental journals from 2003 to 2012: a bibliometric analysis. PLoS One. 2015; 10(3): e0119503. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDos Anjos LM, Rocha AO, Magrin GL, et al.: Bibliometric analysis of the 100 most cited articles on bone grafting in dentistry. Clin. Oral Implants Res. 2023; 34(11): 1198–1216. PubMed Abstract | Publisher Full Text\n\nRocha AO, Anjos LMD, Vitali FC, et al.: Tooth Bleaching: A bibliometric analysis of the top 100 most-cited papers. Braz. Dent. J. 2023; 34(2): 41–55. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLima TO, Rocha AO, Dos Anjos LM, et al.: A Global Overview of Guided Endodontics: A Bibliometric Analysis. J. Endod. 2024; 50(1): 10–16. PubMed Abstract | Publisher Full Text\n\nHamadallah HH, Alturki KN, Alsulaimani M, et al.: Cleft Lip and Palate Research Trends in Saudi Arabia: A Bibliometric Analysis. Cureus. 2024; 16(1): e52085. PubMed Abstract | Publisher Full Text\n\nMontazeri A, Mohammadi S, Hesari PM, et al.: Preliminary guideline for reporting bibliometric reviews of the biomedical literature (BIBLIO): a minimum requirement. Syst. Rev. 2023; 12(1): 239. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDonthu N, Kumar S, Mukherjee D, et al.: How to conduct a bibliometric analysis: An overview and guidelines. J. Bus. Res. 2021; 133: 285–296. Publisher Full Text\n\nRigo DCA, Rocha AO, Anjos LM, et al.: Dataset Supporting the Bibliometric and Altimetric Review of Artificial Intelligence Use in Cariology. [Dataset]. figshare. 2024. Publisher Full Text\n\nLudlow JB, Timothy R, Walker C, et al.: Effective dose of dental CBCT-a meta-analysis of published data and additional data for nine CBCT units. Dentomaxillofac. Radiol. 2015; 44(1): 20140197. Erratum in: Dentomaxillofac Radiol 44(7):20159003. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee KE, Koo JY, Ye JR, et al.: Three-dimensional analysis of the alveolar ridge profiles of maxillary central incisors in children for autotransplantation. Ann. Anat. 2024 Feb; 252: 152193. PubMed Abstract | Publisher Full Text\n\nVicente A, Wiedel AP, Becker M, et al.: Quantitative assessment of cleft volume and evaluation of cleft’s impact on adjacent anatomical structures using CBCT imaging. Oral Radiol. 2024 Apr; 40(2): 295–303. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBaratieri C, Alves M Jr, Mattos CT, et al.: Changes of pulp-chamber dimensions 1 year after rapid maxillary expansion. Am. J. Orthod. Dentofacial Orthop. 2013; 143(4): 471–478. PubMed Abstract | Publisher Full Text\n\nPearce MS, Salotti JA, Little MP, et al.: Radiation exposure from CT scans in childhood and subsequent risk of leukaemia and brain tumours: a retrospective cohort study. Lancet. 2012; 380(9840): 499–505. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMathews JD, Forsythe AV, Brady Z, et al.: Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ. 2013; 346: f2360. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGoebel MC, Rocha AO, Santos PS, et al.: A Bibliometric Analysis of the Top 100 Most-Cited Papers Concerning Dental Fluorosis. Caries Res. 2023; 57(4): 509–515. PubMed Abstract | Publisher Full Text\n\nMattos FF, Perazzo MF, Vargas-Ferreira F, et al.: Top 100 most-cited papers in core dental public health journals: bibliometric analysis. Community Dent. Oral Epidemiol. 2021; 49(1): 40–46. PubMed Abstract | Publisher Full Text\n\nLagravère MO, Major PW: Proposed reference point for 3-dimensional cephalometric analysis with cone-beam computerized tomography. Am. J. Orthod. Dentofacial Orthop. 2005; 128(5): 657–660. PubMed Abstract | Publisher Full Text\n\nTriggle CR, MacDonald R, Triggle DJ, et al.: Requiem for impact factors and high publication charges. Account. Res. 2022; 29(3): 133–164. PubMed Abstract | Publisher Full Text\n\nFastuca R, Meneghel M, Zecca PA, et al.: Multimodal airway evaluation in growing patients after rapid maxillary expansion. Eur. J. Paediatr. Dent. 2015; 16(2): 129–134. PubMed Abstract\n\nSalifou O: U of A rises 15 places to rank among world’s top 100, fourth in Canada in latest QS rankings. Folio. 2024. Accessed 26 June 2024. Reference Source"
}
|
[
{
"id": "345091",
"date": "18 Dec 2024",
"name": "Çiğdem Şeker",
"expertise": [
"Reviewer Expertise Oral diagnosis",
"Dentomaxillofacial 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\nVisualization of collaboration networks using VOSviewer enhances the study scientifically and visually. The benefits of CBCT in specific areas such as maxillary expansion, endodontic treatment and cleft lip and palate management are well highlighted. The study provides important scientific data by analyzing global trends in the use of CBCT in pediatric dentistry, leading countries, institutions and authors.\nIf I may make a suggestion: 1. I could not find any information in the sources cited in the introduction regarding the issue of CBCT minimizing metal artifact formation. On the other hand, this is mostly possible with software programs such as the metal artifact reduction algorithm. I recommend reviewing this information and references.\n2. Radiation risks associated with the use of CBCT in pediatric patients are discussed, but no recommendations for more detailed safety protocols are made. If available in the studies, this topic can also be discussed.\n3. When analyzing the study themes, do you have any idea about the reason for the increase in 2023? If so, please specify.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "342266",
"date": "07 Jan 2025",
"name": "Beenish Fatima Alam",
"expertise": [
"Reviewer Expertise 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\nAbstract:\n\nrephrase this line 'This study provides an overview of CBCT in paediatric dentistry' as This study provides an overview regarding the role of CBCT in paediatric dentistry.\nMethods:\nTimeline for data collections needs to be added.\nDate when the online search was conducted on WOS needs to be added in methods and in abstract.\n\nHow were papers scrutinized/selected? this processs needs to be described in details. You can add a prisma flow chart to better explain the process of paper selection.\n\ninclusion criteria and exclusion criteria need to be clearly described.\n\nDiscussion:\n'Publishing Journals' more details regarding influence of impact factor of journals and why authors prefer to publish in such journals needs to be discussed.\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/13-1320
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https://f1000research.com/articles/13-258/v1
|
10 Apr 24
|
{
"type": "Case Study",
"title": "Maternal and perinatal death surveillance and response in Bangladesh: A case study on measuring impact through health information systems",
"authors": [
"Abu Sadat Mohammad Sayem",
"Jens Johan Kaasbøll",
"Abul Halim",
"Dr. Abu Sayeed Md. Abdullah",
"Jens Johan Kaasbøll",
"Abul Halim",
"Dr. Abu Sayeed Md. Abdullah"
],
"abstract": "The health sector in Bangladesh is thriving, and the Maternal and Perinatal Death Surveillance and Response (MPDSR) program has been in place to investigate the causes of maternal and perinatal death. This study aimed to investigate the availability of information systems for measuring the status of an MPDSR program and the planning process and actions developed based on real-time information. This study delved into innovative information systems that can be used to monitor and measure the impact of health programs. The study included both the primary and secondary data. A total of six key informant interviews were conducted to explore the enablers and strengths of information systems. Secondary data were collected from government websites and MPDSR action plans. This study highlights the potential and challenges of governmental health information systems in notifying maternal and neonatal deaths. While the current notification rates are not up to national standards, it is encouraging to see health managers develop action plans and address this issue. The MPDSR information system is a valuable tool to help health managers measure changes in maternal and perinatal mortality rates and design locally targeted interventions. However, several obstacles must be addressed, such as insufficient data, lack of monitoring, and irregularities in MPDSR review meetings. By finding ways to overcome these challenges, we can unlock the full potential of MPDSR and improve maternal and neonatal health outcomes. The success of an MPDSR program relies on how the information is utilized to take action and measure the outcome. Advanced information systems, such as health dashboards, scorecards, and administrative data, can play a vital role in measuring the progress and impact of a program. The primary challenge lies in capturing all deaths, including their causes, and having the capacity to analyze the data effectively to develop action plans for health managers.",
"keywords": [
"Health information systems",
"dashboard",
"Maternal and perinatal deaths",
"impact measurement"
],
"content": "Introduction\n\nThe health information system in Bangladesh has been transformed from a paper-based and disorganized system to a web-based system called District Health Information Software (DHIS2).1 With over 16,000 health organizations adopting DHIS2 in 2013, Bangladesh has emerged as one of the largest DHIS2 deployers in the world.2 As a result, the health system’s quality of care has been enhanced by adopting tools such as Maternal and Perinatal Death Surveillance and Response (MPDSR), which the WHO and UNICEF recommend. The program notifies the death of the mother and newborn, followed by a death review to identify causes and develop a response to prevent future deaths.3\n\nThe program was piloted in one district in 2007 and was gradually scaled to all 64 districts. It is within the existing health system to identify and examine the causes of maternal and neonatal deaths and stillbirths, both within the community and at the facility.4 The data for the MPDSR were initially collected in papers—a group of professionals reviewed the document to identify the cause of death and associated factors. The recommendations were then sent back to the health managers. This process usually takes more than six months to determine the cause of death and to act accordingly.\n\nGlobally, there was a 44% reduction in maternal deaths, from 532,000 in 1990 to 303,000 in 2015.5 In Bangladesh, the Maternal Mortality Ratio (MMR) declined between 2001 and 2010, but has now plateaued compared to 2016. Although progress has been impressive in the past, it is necessary to achieve Sustainable Development Goals in ending preventable maternal deaths through a renewed focus on accountability and actions.6\n\nOne of the essential pillars of the WHO’s six building blocks is the health management information system, which is crucial for the evaluation and performance measurements of any health program. Health management information systems form the foundation of data-driven decision-making at both the national and subnational levels.7,8 While designing a health information platform, it is crucial to understand that the need for the quantity and comprehensiveness of data at the district [or equivalent] and lower levels is generally more significant than that at the national level.9 One of the challenges of health management in developing countries is the existence of weak accountability and feedback practices.10 At the national level, data is necessary for a broader scope of policymaking. At the district and sub-district levels, local data are of immense value in allocating resources, capacity-building health workers to improve existing service delivery and quality and introducing new services.11 With data available as evidence, local health managers can formulate and justify short- and long-term planning, with the involvement of community people and stakeholders.11\n\nThe DHIS2 system has presented Kenya with unprecedented potential to move from the era of an unreliable and fragmented HIS system to an ideal situation of availability and use of quality health information for rational decision-making.12 Sri Lanka has a DHIS2 platform linked to CRVS data. This ensures that no deaths go unreported, which has compelled healthcare managers to take actions that have effectively reduced maternal deaths.13 The Commission on Information and Accountability (CoIA) in 2011 and the recent Global Strategy for Women’s, Children’s, and Adolescents’ Health (2016–2030) recommend accountability as a core principle driving progress in health outcomes.6\n\nThe National Core Management Information Systems (MIS) committee, chaired by the directorates, meets monthly to obtain feedback on technical issues and monitor data from all the districts.14 The platform has helped reduce the administrative burden on the health system, reducing silos, and streamlining processes within a national data warehouse. Within the MPDSR program, a community healthcare provider enters data related to the death of a mother or newborn at the grassroots level into the DHIS2. By contrast, healthcare managers at national and subnational levels can learn about an event in real time from the same platform.15 The final causes of death are determined at the divisional level by Gynecologists, Obstetricians, and Neonatologists based on death review forms, and that information is also entered into the DHIS2.16\n\nThis study thoroughly analyzed the current information systems utilized in the MPDSR program. The qualitative interviews revealed significant gaps and barriers impeding evidence-based planning and action.\n\n\nMethods\n\nThe ethical clearance for the study was obtained from the Ethical Review Committee of Centre for Injury Prevention and Research, Bangladesh (ERC review number: CIPRB/ERC/2020/08, Date of approval: 27 February 2020). A consent form was developed and used for each interview. Written informed consent was obtained from the respondents before starting the interviews. The consent form clearly stated that their participation is voluntary and can be stopped at any time for any reason and that they can answer some questions and skip others if they wish. The research was guided by ethical considerations, including child safeguarding, sensitivity, openness, confidentiality, data protection, reliability, and independence.\n\nThe study used mixed methodology to understand the given research problem. The mixed method has emerged as a major methodological approach across social science, and many view this as a third approach alongside qualitative and quantitative research.17 Both primary and secondary data were collected and analyzed in this study. We selected 27 districts in which MPDSR implementation matured in 2019. We collected data on reproductive maternal, neonatal, child, and adolescent health (RMNCAH) from 27 districts in 2019 and 2021 (January–December). The selected districts were mainly low-performing and high-priority, based on key performance indicators. Data were collected from the Government of Bangladesh website (DGHS dashboard). Health managers’ approved MPDSR action plans were collected from seven districts (2019-20 plans). The quantitative data collected were based on maternal and perinatal deaths notified and reviewed using the DHIS2. We conducted six key informant interviews at the national level with the National MPDSR core committee members. The participants were chosen based on their relevance to the program for an extended time.\n\nKey Informant Interviews (KII) were conducted in 2021 using a standardized guideline as part of the primary data collection to complement the findings of the document review.25 The KII guidelines were provided by the author. It was pilot-tested before the interview. Two trained anthropologists collected the primary data through face-to-face interviews with key respondents. The interviewers were MBBS with MPH backgrounds. They were experts in taking KIIs of health and family planning managers at the national and district levels. First, a communication letter was circulated from the Line Director, MNC&AH, DGHS, to conduct these KIIs with respondents. Then, the interviewers communicated with the respondents over the phone and booked their time for the interviews. A guideline for KII and a consent form in Bangla was developed by the research team for this data collection. The respondents who were highly engaged with the MPDSR program in Bangladesh were selected purposively. A permission letter was collected from the government for data collection. The data collectors communicated with the selected key informants over the cell phone and booked their time for an interview. Then, they visited the respondents’ work and conducted the interview. Before starting the interview, consent was received for the interview and audio recording. The duration of each interview (KII) was 30-45 minutes. Audio records were included in each interview. The transcription was developed from audio recordings, and the translation was conducted from Bangla to English. A thematic analysis was then conducted using qualitative methods. KIIs were performed to understand critical stakeholders’ beliefs about MPDSR data use and how the implementation of MPDSR could be improved by identifying barriers. The respondents (Table 1) were specifically asked about the gaps in the MPDSR implementation and process and their recommendations for improving the process for a higher impact.\n\nThis study also collected district MPDSR action plans developed by health managers through workshops and funded for implementation. The plans were implemented in the Sylhet, Maulvibazar, Bandarban, Cox’sbazar, Jamalpur, Netrokona, and Gazipur districts.\n\nSecondary data were collected from public governmental health websites. There was a specific dashboard on the MPDSR program within the health dashboard. The MPDSR dashboard produced tables, pie charts, and trends. To provide a quick overview of the performance at the district level, a color-coded tool/table can be generated, with green indicating on-track, yellow indicating progress, and red indicating not on-track. Consent and permission were obtained from the Ethical Review Committee and the Government to access all data used in this study; thus, ethical clearance was ensured. Reviewing the Reproductive, Maternal, Neonatal and Child Health (RMNCH) scorecard was another method applied in this study to observe progress in the health indicators in the MPDSR data. The baseline was 2019 and compared with 2021. The RMNCH scorecard data was collected from 27 districts from the government website (Figure 1). The data from the website was extracted in 2022.\n\nThe causes of death data were also entered into DHIS2 after an expert’s review at the district level. The districts organize a one-day-long workshop with all their sub-district health managers to develop a plan based on the available data in DHIS2. Frequency analysis was used for MPDSR key actions in the seven districts and presented in a tabulated form. Quantitative data on death notifications were also analyzed in a Microsoft Excel (Version 2308) spreadsheet, shown in the Figures 2,3 and 4.\n\n\nResults\n\nIt is worth noting that Bangladesh is one of the few countries that uses real-time MPDSR data through a dashboard, which the MOH creates for monthly monitoring. The study team examined data to measure performance in 27 districts and identify gaps in information systems. This dashboard is used for various meetings, including MPDSR committee meetings, monthly health coordination meetings, MPDSR action plan workshops, video conferences, and national MPDSR core committee meetings. It is also important to mention that the WHO provides projection-based population data to estimate the number of children born to each administrative unit.\n\nIn 2019, only 63% of the estimated 2056 maternal deaths were reported, and health workers reviewed only 32% of notified cases. According to the national MPDSR guidelines, the target for maternal death review was 100% of notified cases. This indicates the need for health workers to visit the deceased mother’s home to increase notifications and review the cause of death. Facility maternal deaths are notified and reviewed, with much better performance compared to community MPDSR. 76% of the cases were reviewed at the facility (Figure 2).\n\nAccording to the national MPDSR guidelines, it is recommended that 10% of neonatal deaths be reviewed to determine the causes of death and to identify social barriers. However, the performance of neonatal death surveillance in capturing community data is lacking, with only 29% of cases being recorded. Additionally, health workers reviewed 46% of the cases, even though this was not required (Figure 3). However, the performance in reviewing facility deaths was satisfactory. Identifying the right target can help health workers reduce their workload by targeting appropriate number of cases.\n\nWe attempted to examine how the performance of MPDSR could be evaluated using data from the dashboard. We observed that the death notification system is unique in all 64 districts and captures data from around 5000 unions (lowest administrative units) through health assistant reports. The data show that the system captures 45% of maternal and 26% of neonatal deaths nationally (Figure 4). This is to mention that private hospitals and urban health facilities are not fully reporting through DHIS2. In this case, the selected districts performed better than the national level in terms of death notification, which was common for all districts.\n\nThis study found that the current information system can capture important qualitative data to aid health managers in evidence-based planning. According to the three-delay model, maternal mortality is linked to delays in three areas: (1) deciding to seek care, (2) reaching the healthcare facility, and (3) receiving care. By analyzing the MPDSR dashboard, health managers could identify the major causes of maternal and neonatal deaths at different levels, which helps in planning. The maternal death review contains information about the cause of death and the three delays: decision-making, transport, and delays in receiving services. The MPDSR dashboard displays the percentage of different causes of maternal and neonatal deaths, which helps health managers prioritize their efforts. Figure 5 below shows that hemorrhage is the leading cause of maternal death, whereas birth asphyxia is the primary cause of neonatal death.\n\nWe collected detailed action plans from seven districts to determine whether the actions were linked to the information systems. Health managers developed MPDSR action plans annually through a 1-2 day-long workshop. All team members analyze the data and develop a 6-to 12-month plan for the district. The senior gynecologist and neonatologist led the technical expertise for interventions, and health managers develop key actions to reduce mortality. We observed that the key actions were being developed in different thematic groups by the cause of death for maternal and neonatal deaths. Some cross-sectoral health-system barriers have been identified. After reviewing the documents, we summarized the key actions to reduce maternal and neonatal deaths in the seven districts (Table 2). During the workshops, health managers identified the major causes of maternal and neonatal deaths along with barriers. The experts recommend solutions to these problems and develop action plans that were costed for implementation. The actions in Table 2 were linked to the causes of death from the dashboard. The persons responsible for implementing these action plans at the community level were health education officers, community healthcare providers, health inspectors, and local elite persons in the community. At the facility level and in the MPDRS committee, the Residential Medical Officer, Medical Officer, Civil Surgeon, Upazila Health and Family Planning Officer, and Upazila Family Planning Officer were responsible for implementing actions to reduce death. The quality of MPDSR action plans varied from district to district. Significant gaps in data completeness have been addressed in the action plan by authorities to improve data entry.\n\nThis study analyzed maternal and neonatal indicators to evaluate the impact of information systems from 2019 to 2021 (Table 3). Based on the scorecard system developed by MOH&FW for key indicators, it was revealed that all seven districts in 2019 had inadequate coverage of specific services, including the registration of pregnant mothers, antenatal care (ANC) and postnatal care (PNC) services, and delivery by skilled birth attendants. This highlights the need to improve these areas to ensure better health care services. The RMNCAH dashboard generates a color-coded table that provides a quick overview of performance at the district level. Green indicates on track, yellow indicates progress, and red indicates not on track (Table 3). The information system can track the progress of health indicators in a district for comparison and trend analysis among health workers. This information system can track the progress of health indicators in a district for comparison and trend analysis. Despite the COVID pandemic, the seven districts that developed MPDSR action plans could measure progress using many indicators. This is to remind you that the COVID pandemic has heavily impacted routine essential health services such as ANC, facility delivery, routine immunization services, and PNC. In 2021, many efforts have been made to restore the services to the baseline year (2019). The impact was impressive in most cases, except in a few districts, which require further investigation.\n\nThis study reviewed the scorecard of the MPDSR program and found that its key performance indicators were linked with maternal and neonatal mortality rates. The program’s performance dashboard can visualize its impact based on surveys and routine data. Most indicators showed positive changes, except in the Bandarban and Gazipur districts, where mortality and service coverage decreased. Pregnancy registration, delivery antenatal 4th visits coverage, and postnatal care increased in Jamalpur and Maulvibazar, where the impact of reducing MMR was the highest. The data were subject to verification but could be discussed during the MPDSR meetings.\n\nThe interviews informed recommendations for improving MPDSR in developing countries.\n\nStrengthening the health workforce through capacity building and incentives\n\nMPDSR involves capacity-building opportunities, such as training and logistics, as well as motivating healthcare workers. Training helps workers understand the importance of death reviews and enables them to use this information during planning. Engaging professional associations and providing incentives can motivate workers to ensure their success. One of the interviewees mentioned that “There was remuneration for death review before, and now there is no incentive for death review and social autopsy in the field. The staff needs to be accountable for this work.”\n\nLinking MPDSR information systems with quality improvement programs\n\nMPDSR plays a crucial role in enhancing the quality of healthcare services. The results derived from the facility death review process should be connected with the quality improvement cycle at the national, subnational, and facility levels through QI/MPDSR committees. Every intervention at the facility level must be linked to the Plan Do Check and Act (PDCA) cycle, ensuring continuous improvement and monitoring through information systems.\n\nProviding a sustainable and trouble-free information system\n\nIt is essential to provide technical assistance to ensure accurate data entry at all levels, especially at the district and upazila levels. With proper guidance and support from an IT cell/department, technical issues related to data entry, data accuracy, and server issues may be minimized or resolved.\n\nBetter coordination between policymakers and field-level staff\n\nCoordination at all levels needs to be strengthened to ensure better implementation and participation of field-level health workers and their supervisors. During the national MPDSR core committee meetings, policymakers need more involvement to change the national strategy and address the findings from lower tiers, such as incentivizing success and appreciating champions at the national level. The managers mentioned that the MPDSR initiative aims to improve maternal and perinatal health outcomes by fostering a collaborative and comprehensive approach. To achieve this, the organogram must include UNICEF, WHO, CIPRB, and the ministry for death notification, data analysis, DHIS2 updates, coordination, and collaboration. By bringing together various stakeholders, the initiative can significantly impact reducing mortality rates and improving healthcare systems, aligning with global efforts to improve maternal and perinatal health outcomes. One of the managers said that:\n\n“The coordination needs to be improved within DGHS and DGFP. The staff members need to be rewarded for the work.”\n\nRevision of National MPDSR guideline\n\nMost key stakeholders believe that there is a need to revise the current MPDSR guidelines developed in 2014. The new guidelines should clarify certain functions and add improvements to the existing framework/process, as per the new WHO guidelines, including stillbirth.\n\n“There is an urgent need to revise the MPDSR guideline based on the lessons learned from the experiences of implementation. We are currently revising the MPDSR guidelines, including integration of stillbirth.”\n\nPromote standardized response processes.\n\nThe actions taken during the MPDSR workshops were mostly similar and broad. Some solutions, such as HR and funds, are not manageable by local health managers. This includes the systematic follow-up and implementation of recommendations across system levels using a tracking system. The MPDSR committee can review the actions and define a set of common actions for all districts as a recommendation.\n\nLegal enforcement of death reporting\n\nIn many countries, death reporting is required by law, which makes it essential for healthcare providers to report all types of deaths, including maternal and neonatal deaths and stillbirths. This will further strengthen the information system for the MPDSR. One respondent stated that:\n\n“In Bangladesh, recently, with the support of UNFPA, progress has been made by the parliament to make death reporting a legal requirement. Soon, maternal and neonatal deaths and stillbirths will be more accurately reported, which will aid in the success of MPDSR scale-up and implementation.”\n\nMonthly district-level cause-analysis\n\nThe stakeholders recommend the provision of monthly cause analysis workshops at the district level instead of conducting the workshop at a higher level. At the district level, gynae-and-pediatric consultants are present, so conducting cause analysis workshops monthly using the local information system is possible. This will improve the accuracy and speed of local action plan development.\n\nMPDSR-monitoring cell\n\nPolicymakers suggest the formation of a separate MPDSR-focused cell to concentrate on the successful implementation of the program, including partners supporting it in different districts. The capacity of MPDSR data analysis needs to be further strengthened by local health managers.\n\n\nDiscussion\n\nPublic health surveillance is the ongoing systematic collection, analysis, and interpretation of health data. This includes disseminating the resulting information to health managers who need it to develop actions. MDSR continuously links the health information system and quality improvement processes, both locally and nationally. It includes routine identification, notification, quantification, and determination of causes and modifiable causes of all maternal deaths as well as using this information to respond to actions that will prevent future deaths.18\n\nRMNCH scorecards and MPDSR dashboards were innovative tools for visualizing and converting data into information for use. The scorecard alerts program managers and decision-makers to be aware of areas that continuously record low performance and lack progress, as well as those needing more attention and action.19 The innovation here was the integration of scorecard and dashboard functionalities that help track progress and drive actions.\n\nThe study found that information systems could identify gaps in measuring MPDSR performance, such as coverage of maternal death notifications, pregnancy registration systems, and effective interventions to improve awareness among pregnant mothers. Moreover, based on this information, health managers have developed interventions for their districts based on context. An information system can measure the effectiveness of an intervention and determine whether it has been successful. For example, in Bandarban, a hilly terrain, the interventions listed in the plan did not work out, and as per the scorecard, the MMR went up. The managers mentioned conducting video conferences to monitor progress regularly and to improve health managers’ accountability.\n\nThe Southeast Asia region WHO report revealed that out of 10 countries, only three hold national-level meetings twice yearly on MPDSR committees.20 In Bangladesh, health managers recommend that the government and partners collaborate to implement the MPDSR and establish accountability and laws for death notification.\n\nIn Ethiopia, the identification and detection of maternal and perinatal deaths are poor relative to the national target. However, the percentage of maternal death reviews is higher in Ethiopia than in Kenya and Guinea.21 In Guinea, it was found that healthcare providers underreport maternal death for fear of being accused and punished,22 which was not the case in Bangladesh. It was also revealed that out of 23 study districts in the country, three did not have any maternal death review committee, and among the reported maternal deaths, only half were reviewed.22 Poor reporting and record-keeping results in poor documentation in Nigeria.23 Bangladesh’s robust information systems have facilitated more significant progress than those of Kenya, Ethiopia, and Guinea.\n\nThis study identified common actions to prevent maternal and perinatal deaths. Similar measures are also taken in other countries, which include proper training of health care providers for the management of complications,20 motivating people for institutional delivery,22 ensuring sufficiency of medicine at the facility, ensuring the availability of transport facilities,22 making better coordination between referring and referral intuition, confirming the birth plan for every woman,20 proper monitoring and evaluation, strengthening MPDSR implementation by regular meetings at the district level,23 and ensuring adequate funding.22 Our study also resonates with similar findings from interviews at the national level and from health managers during the development of action. Information systems at the lower level enable health managers to discuss similar barriers and develop key actions.\n\nAction plans should be taken according to the cause of death, and it should be feasible to apply them according to the country’s context.24 Our study revealed that the action plans taken in our study districts are heavily data driven. Although the number of deaths, HR, and facility readiness were not similar, most actions were similar between the districts. Moreover, there was no tracking of the actions, and no information on how the action was implemented to achieve the goal. This is one of the areas in which the country needs further attention to design more effective interventions to reduce deaths. This study found that an MPDSR dashboard could be a helpful solution for health managers to easily find data for the program’s planning, monitoring, and evaluation. This must be integrated with motivational awards or incentives through events, such as the National Health Minister’s Award of Emergency Obstetric Care Awards. There is a need for capacity building for health managers to strengthen monitoring through the MPDSR dashboard, which could help field health workers work more cohesively.\n\nThe main challenges of MPDSR implementation are poor documentation, underreporting, and a lack of regular monitoring and feedback at the district level.20,22,24 The government portal in Bangladesh explicitly compares death reviews and notifications at both the facility and community levels thanks to the population information system in place. Although most studies have been conducted at the facility level, it is crucial to conduct more studies at the community level to identify obstacles to implementing this approach. Examining death reviews and notification processes in different contexts and levels is essential to achieve better outcomes. The government portal in Bangladesh explicitly compares death reviews and notifications at both facility and community levels. Although most studies have been conducted at the facility level, it is crucial to conduct more studies at the community level to identify obstacles to implementing this approach. Examining death reviews and notification processes in different contexts and levels is essential to achieve better outcomes.\n\n\nConclusion\n\nBangladesh implemented innovative methods for visualizing MPDSR information systems. This allowed health managers to monitor, design action plans, and evaluate their impact in real time. Data quality plays a significant role in decision making at both the local and policy levels. Although routine data showed decreased maternal and neonatal mortality in most of the implemented districts, further evaluation is recommended through data triangulation and independent assessment. The existing information system enables the program to track the progress of every step of the MPDSR. However, monitoring and accountability by managers require strengthening. The availability of MPDSR information systems created a culture of evidence-based planning and monitoring through visualization platforms, such as the RMNCAH scorecard and MPDSR dashboard. Thus, health managers can now make evidence-based decisions. A strengthened routine information system has reduced dependency on survey data. However, there is a lack of tracking interventions after the development of action plans, making it difficult to measure the effectiveness of each intervention. Nevertheless, information systems can produce program impact results. Improving the data quality of MPDSR through proper monitoring is essential for success. Real-time data from MPDSR can identify low-performing districts. Strengthening accountability in the program could help Bangladesh achieve its SDG goals.",
"appendix": "Data availability\n\nThe data on the website can be accessed from the government website using the following url:\n\n- MPDSR dashboard https://dashboard.dghs.gov.bd/pages/dashboard_mpdsr_performance.php\n\n- RMNCAH scorecard https://dashboard.dghs.gov.bd/pages/dashboard_rmnch.php\n\nAll routine data pertaining to the government can be found on the website and is accessible from anywhere. There are various dashboards available for specific programs, but for the purposes of this research, two dashboards have been utilized: the MPDSR dashboard and the RMNCAH scorecard. The MPDSR dashboard is used by program managers to monitor the progress of implementation, while the RMNCAH scorecard is employed to track coverage indicators and measure progress over time.\n\nFigshare: MPDSR-Bangladesh data. https://doi.org/10.6084/m9.figshare.24710166. 25\n\nThe project contains the following underlying data:\n\n- Paper 2 MPDSR Raw data file final.xlsx\n\n- Interview transcript MPDSR redacted.pdf\n\nFigshare: MPDSR-Bangladesh data. https://doi.org/10.6084/m9.figshare.24710166. 25\n\nThe project contains the following extended data:\n\n- Guideline KII_National level_MPDSR IR.pdf (Interview guides)\n\n- MPDSR Figure 1.tiff\n\n- MPDSR Figure 2.tiff\n\n- MPDSR Figure 3.tiff\n\n- MPDSR Figure 4.tiff\n\n- MPDSR Figure 5.tiff\n\n- MPDSR Table 1.tiff\n\n- MPDSR Table 2.tiff\n\n- MPDSR Table 3.tiff\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\nUNICEF ROSA: Health System Strengthening: Transforming the health information system in Bangladesh | UNICEF South Asia. UNICEF; 2019. Reference Source\n\nKhan MAH, Cruz V de O, Azad AK: Bangladesh’s digital health journey: reflections on a decade of quiet revolution. WHO South East Asia J. Public Health 2019; 8(2): 71–76. Publisher Full Text\n\nKinney MV, Walugembe DR, Wanduru P, et al.: Implementation of maternal and perinatal death reviews: a scoping review protocol. BMJ Open. 2019; 9(11): e031328. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBiswas A: Shifting paradigm of maternal and perinatal death review system in Bangladesh: a real time approach to address sustainable developmental goal 3 by 2030. F1000Res. 2017; 6: 1120. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWHO, UNICEF, UNFPA, World Bank Group, United Nations Population Division: Trends in Maternal Mortality: 1990 to 2015. Geneva: WHO; 2015.\n\nBandali S, Thomas C, Hukin E, et al.: Maternal death surveillance and response systems in driving accountability and influencing change. Int. J. Gynecol. Obstet. 2016; 135(3): 365–371. PubMed Abstract | Publisher Full Text\n\nIndicators, A. H. O: Monitoring the building blocks of health systems. Geneva, Switzerland: WHO Document Production Services; 2010.\n\nSandiford P, Annett H, Cibulskis R: What can information systems do for primary health care? An international perspective. Soc. Sci. Med. 1992; 34(10): 1077–1087. Publisher Full Text\n\nSenyoni WF, Kimaro HC, Braa J, et al.: An institutional perspective on the adoption of open dashboard for health information systems in Tanzania. Information and Communication Technologies for Development. Strengthening Southern-Driven Cooperation as a Catalyst for ICT4D: 15th IFIP WG 9.4 International Conference on Social Implications of Computers in Developing Countries, ICT4D 2019, Dar es Salaam, Tanzania, May 1–3, 2019, Proceedings, Part I 15. Springer International Publishing. 2019; pp. 272–283.\n\nMoyo CM, Frøyen MH, Sæbo JI, et al.: Using performance league tables to promote accountability and feedback in health management in Malawi. IFIP WG. 2016, December; Vol. 9.\n\nChaulagai CN, Moyo CM, Koot J, et al.: Design and implementation of a health management information system in Malawi: issues, innovations and results. Health Policy Plan. 2005; 20(6): 375–384. PubMed Abstract | Publisher Full Text\n\nKaruri J, Waiganjo P, Daniel ORWA, et al.: DHIS2: the tool to improve health data demand and use in Kenya. J. Health Inform. Dev. Ctries. 2014; 8(1).\n\nHazard RH, Buddhika MP, Hart JD, et al.: Automated verbal autopsy: from research to routine use in civil registration and vital statistics systems. BMC Med. 2020; 18: 1–11. Publisher Full Text\n\nBegum T, Khan SM, Adamou B, et al.: Perceptions and experiences with district health information system software to collect and utilize health data in Bangladesh: a qualitative exploratory study. BMC Health Serv. Res. 2020; 20(1): 1–13. Publisher Full Text\n\nBiswas A, Ferdoush J, Abdullah ASM, et al.: Social autopsy for maternal and perinatal deaths in Bangladesh: a tool for community dialog and decision making. Public Health Rev. 2018; 39(1): 1–7. Publisher Full Text\n\nMinistry of Health and Family Welfare [MoHFW]: National Guideline on MPDSR 2016.[cited 2020 July 28]. Reference Source\n\nClark VLP, Creswell JW, Green DON, et al.: Mixing quantitative and qualitative approaches. Handbook of emergent methods. Vol. 363.2008; pp. 363–387.\n\nWorld Health Organization: Maternal death surveillance and response: technical guidance information for action to prevent maternal death. World Health Organization; 2013.\n\nHanifi SMA, Hossain A, Chowdhury AH, et al.: Do community scorecards improve utilisation of health services in community clinics: experience from a rural area of Bangladesh. Int. J. Equity Health. 2020; 19: 1–11. Publisher Full Text\n\nWHO: Strengthening Country Capacity on Maternal and Perinatal Death Surveillance and Response: Report of a South-East Asia Regional Meeting, 16-18 February 2016.2016.\n\nAyele B, Gebretnsae H, Hadgu T, et al.: Maternal and perinatal death surveillance and response in Ethiopia: achievements, challenges and prospects. PLoS One. 2019; 14(10): e0223540. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMillimouno TM, Sidibé S, Delamou A, et al.: Evaluation of the maternal deaths surveillance and response system at the health district level in Guinea in 2017 through digital communication tools. Reprod. Health. 2019; 16: 1–11. Publisher Full Text\n\nSageer R, Kongnyuy E, Adebimpe WO, et al.: Causes and contributory factors of maternal mortality: evidence from maternal and perinatal death surveillance and response in Ogun state, Southwest Nigeria. BMC Pregnancy Childbirth. 2019; 19(1): 1–8. Publisher Full Text\n\nSchiavone F, Leone D, Caporuscio A, et al.: Revealing the role of intellectual capital in digitalized health networks. A meso-level analysis for building and monitoring a KPI dashboard. Technol. Forecast. Soc. Chang. 2022; 175: 121325. Publisher Full Text\n\nSayem ASM: MPDSR-Bangladesh data. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "280803",
"date": "25 Jun 2024",
"name": "Tahmina Begum",
"expertise": [
"Reviewer Expertise To make this article reproducible by other researchers",
"a detailed description of the study methodology",
"data source",
"analysis plan needs to be well described"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a very informative article and has all the merits of indexing. However, to make the study reproducible by other researchers, it requires more detail. I have added some points for consideration for the next round of revision. Data flow in the introduction should support the rationale of conducting this study in the context of MPDSR.; what has been done so far, what new things are we proposing, and is there any successful evidence from other LMICs using our proposed approach/ has the new approach been successful in other MNH health service delivery? Methods:\nEthics would come next after describing the study design and setting. This is not justified to explain mixed method as 3rd, it is better to drop this line, at best author can say qual findings were used to explain the data gap……….. observed in quantitative findings. Be specific about what you mean by primary and secondary data. Publicly available data from the DGHS dashboard is your secondary data source here. Did the patients provide consent to use their data for research? The research is focused on MPDSR, but the justification of analysis RMNCAH data is not clear from the methods section. Though the author specifies the primary data source in 3rd paragraph, different terminology “Document review was used to explain the quantitative data source. What documents did the author review as part of the Quan data source has not been specified before. Nothing was mentioned about the analysis plan for the qualitative data. How did they divide data under the theme, what themes were used, how did you code, a-priori/reflexive /inductive …… manual /software? What is the RMCH scorecard, and what are the components? How did u analyze them? Figure 1.27 The study site seems clustered on the south side of the map, which means the rest of the sites are well-performing. Did the author use convenient sampling, if so, how it is going to affect the generalizability of your findings?\nResult:\n\nThe result section is only to present findings, we can not add any argument or justification, For example, the below 2 lines do not fit in the result section. “It is also important to mention that the WHO provides projection-based population data to estimate the number of children born to each administrative unit”. For all the figures Axis titles are not unique and check for spelling mistakes. Does not make sense to specify that Bangladesh and the intervention district are in the same graph with different bars. Please explain how the estimated maternal and neonatal death numbers were calculated/projected in your method section.\nDiscussion:\n\nPlease add an opening paragraph with key findings from your paper.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Not applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": [
{
"c_id": "12728",
"date": "05 Nov 2024",
"name": "Abu Sadat Mohammad Sayem",
"role": "Author Response",
"response": "Dear Reviewer, Thanks for your comprehensive feedback on the article, and much appreciated. I have corrected those in my new version and added more facts to boost further understanding of the manuscript. I have added more information in the introduction based on your comments. Methods: The ethics section has been relocated to a more appropriate position within the document to enhance clarity and coherence. In addition, the methods section has been thoroughly revised to improve its overall readability, and we have incorporated additional details to address your inquiries regarding both primary and secondary data collection methods. I included qualitative analysis techniques, although I faced some constraints due to word limitations that prevented me from elaborating further on this aspect. In the results section, I provided a comprehensive explanation of the RMNCAH (Reproductive, Maternal, Newborn, Child, and Adolescent Health) dashboard. This dashboard serves as an integrated data system that consolidates all relevant maternal and neonatal health information, enabling a better understanding of the outcome and impact-level indicators for Bangladesh. Furthermore, the selection of districts for this study was based on specific criteria, which have been elaborated upon in the methods section to provide greater transparency regarding our approach. Results: The language and writing style of the results section have undergone a thorough revision to enhance clarity and precision. However, it was not possible to modify the Axis title, as it was sourced directly from the MPDSR dashboard, which has been cited in our reference materials. Additionally, the explanation regarding the estimated population figures draws upon an Excel file that was provided by the World Health Organization (WHO) to the government. This Excel file contains comprehensive district-wise data, including detailed calculations that utilize the growth rate projections for each year. This meticulous methodology ensures accuracy and reliability in the population estimates presented. Discussion: It has been improved further."
}
]
}
] | 1
|
https://f1000research.com/articles/13-258
|
https://f1000research.com/articles/13-295/v1
|
18 Apr 24
|
{
"type": "Research Article",
"title": "Could Anemia Impact the Severity of Infections? COVID-19 as an Example",
"authors": [
"Sham ZainAlAbdin",
"Salahdein Aburuz",
"Amal Akour",
"Rami Beiram",
"Munther Alnajjar",
"Derar Abdel-Qader",
"Mosab Arafat",
"Anan Jarab",
"Mohammed Aburuz",
"Sara AlAshram",
"Sara AlJabi",
"Fatima AlSalama",
"Mohammed Al Hajjar",
"Sham ZainAlAbdin",
"Amal Akour",
"Rami Beiram",
"Munther Alnajjar",
"Derar Abdel-Qader",
"Mosab Arafat",
"Anan Jarab",
"Mohammed Aburuz",
"Sara AlAshram",
"Sara AlJabi",
"Fatima AlSalama",
"Mohammed Al Hajjar"
],
"abstract": "Background The association between anemia and severity of infection as well as mortality rates among patients infected with COVID-19 has scarcely been studied. This is the first study UAE aimed to assess the influence of anemia on COVID-19 severity, ICU admission, and mortality rate.\n\nMethods A retro-prospective chart review of hospitalized COVID-19 patients was conducted in a large COVID-19 referral hospital in UAE. The study included adult patients with confirmed COVID-19. Clinical and laboratory data, severity of the disease, ICU admissions, and mortality rates were analyzed and correlated to the presence of anemia among the patients.\n\nResults A total of 3092 patients were included. 362 patients (11.7%) were anemic and most of the cases were between asymptomatic and mild COVID-19 (77.4%, n=2393). Among patients with anemia, 30.1% (n=109) had moderate to severe COVID-19. Statistically, anemia was associated significantly with a higher risk for severe COVID-19 outcome compared to nonanemic patients (AOR:1.59, 95% CI:1.24-2.04, p<0.001). Intensive care unit (ICU) admission was almost 3 times higher among anemic patients compared to nonanemic (AOR:2.83,95% CI:1.89-4.25, p<0.001). In addition, the overall mortality rate of 2.8% (n=87) was 2.5-fold higher in anemic than nonanemic patients (OR:2.56, CI: 1.49-4.06, p<0.001). Moreover, older age (≥48-year-old) and male gender were independent predictors for severe illness (Age: OR=1.26, CI:1.07-1.51, p=0.006; Gender: OR:1.43,CI:1.15-1.78, p<0.001)) and ICU admission (Age: OR:2.08, CI:1.47-2.94, p<0.001; Gender: OR: 1.83, CI:1.12-3.00, p=0.008) whereas only age ≥48 years old contributed to higher mortality rate (OR:1.60, CI:1.04-2.46, p=0.034).\n\nConclusion Anemia was a major risk factor for severe COVID-19, ICU admission and mortality among hospitalized COVID-19 patients. Thus, healthcare providers should be aware of monitoring the hematological parameters among hospitalized patients with COVID-19 and anemia to reduce the risk of disease complications and mortality. This association should also be considered in other infectious diseases.",
"keywords": [
"COVID-19",
"Anemia",
"Severity",
"ICU admission",
"Hospitalization",
"Mortality",
"Hemoglobin",
"Ferritin"
],
"content": "Introduction\n\nAnemia is a global health concern affecting more than 1.62 billion people worldwide (approximately 24.8%).1 The World Health Organization (WHO) defines anemia as a condition in which the number of red blood cells or the hemoglobin concentration within them is lower than normal. Low hemoglobin levels are considered at <120 g/L in females and <130 g/L in males. Based on hemoglobin level, severity of anemia can be categorized as mild (110-119 g/L for females and 110-129 g/L for males), moderate (80-109 g/L) or severe (less than 80 g/L).2 Studies in the Arab region, assessing the clinical characteristics of COVID-19 patients, have not explored the prevalence of anemia nor tested its association with COVID-19 severity and mortality.\n\nCoronavirus disease of 2019 (COVID-19) has become a global pandemic since its outbreak in Wuhan (Hubei Province, China) in December 2019.3 According to the National Emergency Crisis and Disasters Management Authority (NCEMA), more than 700 thousand cases were confirmed, and 2135 deaths were reported in the United Arab Emirates (UAE) until November, 4th 2021 and the rate of developing new cases has increased to 67.0% by 2023 although majority of the people are vaccinated against COVID-19.4 Genetic mutations of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) resulted in the emergence of more contagious variants; hence, increasing cases on daily bases.5 Severe infections, such as COVID-19, are associated with hyper-inflammatory state, which might cause alteration in iron homeostasis.6,7 The main suggested mechanism was explained by increased iron acquisition and retention within macrophages and decreased intestinal absorption of iron. Subsequently, this reduces iron availability for erythropoiesis, decreasing the production of hemoglobin. Altogether, the inhibition of erythropoiesis by inflammatory markers, shortened half-life of erythrocytes and decreased biological activity of erythropoietin induce the development of anemia. In contrast to functional iron deficiency, which is associated with low ferritin levels and elevated transferrin levels, the anemia of inflammation is characterized by low levels of iron and transferrin or reduced saturation of transferrin with iron, while ferritin levels are normal or elevated.6 Furthermore, the presence of anemia has been identified as a major risk factor for hospitalization and mortality in several chronic and inflammatory diseases.6–8\n\nSince systemic inflammation is a common manifestation among COVID-19 patients, the presence of anemia in COVID-19 patients may well enhance disease progression and severity.6 However, the exact correlation is unclear, as whether it is a baseline characteristic of patients, or developed secondary to the inflammatory process of COVID-19. In this regard, studies have investigated the association between anemia and COVID-19 severity and mortality. However, there were some limitations in the literature regarding the prevalence and pathogenesis of anemia in COVID-19, as well as its impact on disease severity and mortality.\n\nAnemia was one of the most common hematologic findings in severe or critically ill COVID-19 patients.9 A study showed a severe disease presentation in terms of prolonged hospitalization and the need for ICU admission or mechanical ventilation. Generally, elevated ferritin levels were related to disease severity. However, anemia was not associated with higher mortality rate.6 However, a recent study found that elevated ferritin levels was a predictor for mortality in COVID-19 patients.10\n\nRecent data showed that anemia was significantly associated with severe illness and higher mortality rate,8,11 especially if anemia was present upon admission.6,8 Moreover, Tremblay et al. found that elevation of red blood cell distribution width (RDW) was a poor prognostic factor in hospitalized patients.12 RDW has been validated as a strong predictor of 30-day mortality, reflecting overall inflammation and oxidative stress.13 Another study reported that anemia induced the development of severe COVID-19 pneumonia.14 All these studies concluded that anemia could be a predictive factor of increasing COVID-19 severity and mortality. However, the available data regarding the association between anemia and COVID-19 severity and mortality are scarce and controversial. Moreover, studies evaluating parameters of severe outcomes failed to demonstrate truly this association in a large considerable sample size.15–17\n\nRemarkably, all the reviewed studies have not clearly classified cases in terms of severity (mild/moderate/severe) or evaluated the actual association between anemia and severity, ICU admission and mortality. Therefore, further studies are required to confirm this association in a larger cohort with definite stratification of severity per se. This is the first study aiming to assess the influence of anemia on COVID-19 severity, ICU admission and mortality rate in hospitalized patients in the UAE.\n\n\nMethods\n\nThis is a retrospective observational study carried out on adult patients (≥18 years old) with a confirmed diagnosis of COVID-19, as measured using polymerase chain reaction (PCR) testing on a nasopharyngeal swab, who were admitted to a large government tertiary care center in Al-Ain city, UAE between March and June 2020. All adult patients diagnosed with COVID-19 during the study period were eligible for inclusion.\n\nThe following were the exclusion criteria\n\n1. Pediatrics (Age <18 years old)\n\n2. Pregnant patients\n\n3. Patients admitted for Surgery\n\n4. Patients with Co-infection with other diseases\n\n5. Patients with Cancer\n\nThis study was approved by Covid-19 IRB committee at the Department of Health in the United Arab Emirates (reference number: DOH/CVDC/2020/1121, 3rd of June 2020). Patients’ information was kept confidential and authors didn’t have access to information that could identify individual participants during or after data collection. Study was performed in accordance with relevant guidelines and regulations. This was a retrospective review patients’ files and therefore consent form is waived and not required.\n\nDuring the period from June to July 2020, an IT engineer retrieved all the patients’ data from the hospital electronic databases for patients admitted from March to June 2020 in an Excel sheet. During the period from July to September 2020, two of the research investigators revised, cleaned, and coded the data independently to check for inter-rater reliability. Any disagreement was discussed between the two investigators. The data was accessed for the purpose of this research during the period from January-June 2022. The collected data encompassed demographic information (age, gender, and BMI) in addition to the death rate (calculated by dividing the number of dead cases by total number of the study sample) and presence of anemia for the purpose of our study. Baseline vital signs upon admission (heart rate, respiratory rate, oxygen saturation, systolic, and diastolic blood pressure) in addition to the most relevant laboratory parameters to anemia, such as (hemoglobin, hematocrit, ferritin, D-dimer, and alkaline phosphatase) were reviewed and analyzed.\n\nAdditionally, clinical manifestations on admission (cough, shortness of breath, fever, sore throat, pain, nausea, vomiting and diarrhea), disease severity (asymptomatic, mild, moderate, severe) related to COVID-19 infection were also presented in this study. The disease severity of COVID-19 was categorized according to the guidelines for diagnosis and treatment of COVID-19 published by the National Institute of Health (NIH) (Overview of COVID-19).18 The NIH has categorized the severity of COVID-19 from no symptoms to critically ill cases into 5 categories: asymptomatic, mild, moderate, severe, and critically illness. However, the authors of this study classified the severity of COVID-19 into two categories since the distribution of patients in these categories is inconsistent and for better tabulation of the findings as follows: 1) Asymptomatic/mild illness: those with confirmed COVID-19 with or without the typical symptoms of the disease with no evidence of dyspnea or abnormal chest imaging, and 2) Moderate to severe/critical illness: those with typical symptoms, evidence of dyspnea, PaO2 of ≥94%, and abnormal chest imaging, with or without respiratory failure/multiple organ dysfunction.\n\nAnemia was defined as hemoglobin (Hgb) levels <12.0 g/dL in females and <13.0 g/dL in males as per the study site reference values. Anemia was further categorized based on hemoglobin levels as follows: mild: 10.0 g/dL to lower limit of normal range (12.0 g/dL in females and 13.0 g/dL in males), moderate: 8.0 to 10.0 g/dL, and severe: below 8 g/dL.14 Anemia diagnosis was also confirmed from the hospital database.\n\nThe primary outcome of this study was to evaluate the association between anemia and COVID-19 severity, ICU admission and mortality in hospitalized COVID-19 patients. A secondary outcome was to investigate the effect of other demographic factors including age and gender on COVID-19 outcomes (disease severity, ICU admission rate, and mortality rate).\n\nThe Statistical Package for the Social Sciences (IBM- SPSS, version 26.0) was used for the statistical analysis of data. Mean and standard deviation (SD) were calculated to present parametric data, while median and interquartile range were calculated for non-parametric data. Categorical variables were described as frequencies and percentages.\n\nChi-square test or Fisher’s exact test was calculated to assess the association between anemia and severity of symptoms (stratified as asymptomatic/mild and moderate/severe cases for patients with or without anemia). Similarly, the ICU admissions and mortality rate were assessed and compared for and between patients with and without anemia using the abovementioned statistics. The differences in laboratory parameters between patients with or without anemia were analyzed using the independent t-test or Mann-Whitney test. A p-value less than 0.05 indicated a statistically significant difference with a confidence interval of 95.0%. Additionally, multivariable logistic regression analysis was performed to confirm the influence of anemia on disease severity, ICU admission and mortality.\n\n\nResults\n\nTable 1 represents the differences in demographics and clinical characteristics of the patients with and without anemia. The study included a total of 3092 patients. The average age of all patients (including anemic and non-anemic) was 44.29±13.42 years old and majority of them were males (77.8%, n=2407). In addition, 11.7% of total patients were previously diagnosed with anemia (n=362).\n\nUnivariate analysis of the biodata showed that anemia was higher among females compared to males (20.9% and 9.1%; respectively, p<0.001). In addition, patients aged 48 years old and older were more likely to present with anemia compared to patients aged between 18 and 47 years old (16.2% and 8.9%; respectively, p<0.001). Furthermore, anemia was more prevalent among patients with BMI ≥30 kg/m2 when compared to patients with lower BMI (15.7% and 10.6%; respectively, p<0.001).\n\nUpon evaluating the relationship between anemia and certain hematological parameters, it was found that D-dimer and ferritin were significantly higher in patients with anemia compared to the non-anemics (p<0.001). In contrast, hemoglobin and hematocrit levels were remarkably lower in patients with anemia (p<0.001) compared to the non-anemics. Further details of the differences of vital signs and laboratory parameters among patients with and without anemia are illustrated in Table 1.\n\nThe majority of patients (77.4%, n=2393) were asymptomatic or had a mild form of the infection. Figure 1 shows the clinical presentation of patients with COVID-19. Cough was the most reported symptom by the patients followed by fever, and dyspnea. Other symptoms, such as loss of smell and taste were rarely reported. Regarding the clinical presentation of symptoms among anemic and nonanemic patients, no statistical difference was found.\n\nTable 2 represents the Bivariate analysis of patients’ characteristics and COVID-19 outcomes (severity of COVID-19, ICU admissions, and mortality rate). The risk of developing moderate to severe symptoms was significantly higher when patients presented with anemia, male gender, and age ≥48 years old. In addition, ICU admission among anemic patients was almost 3 times higher than non-anemic patients, was also more than 2 times higher in patients aged ≥48 years old compared to young-age patients, and 1.5 times higher in males compared to females. Moreover, anemia was significantly associated with over 2.5 times risk of death, as 6.1% of anemic cases died compared to 2.4% of nonanemic cases. Also, patients aged ≥48 years old had almost 2 folds higher risk for mortality compared to younger ages. Further details are illustrated in Table 2.\n\nUpon classifying patients anemia into normal, mild and moderate to severe; severity of COVID-19 was higher in anemic compared to normal patients (p <0.001). On the other hand, moderate-to-severe anemia was associated with greater ICU admissions and mortality rates (p <0.001) as presented in Table 3.\n\nMultivariable logistic regression analysis of anemia and health outcomes among hospitalized patients with COVID-19 is shown in Table 4. After adjustment of gender, ages, BMI and anemia, anemia was shown to be a significantly independent risk factor for severe symptoms (AOR: 1.59, 95% CI: 1.24-2.04, p <0.001), ICU admission (AOR: 2.83, 95% CI: 1.89-4.25, p <0.001), and higher mortality rate (AOR: 2.46, 95% CI: 1.49-4.06, p <0.001). In addition, male gender and age (≥48-year-old) were independent risk factors that significantly contributed to developing moderate severe COVID-19 and increasing the rate of ICU admissions. Also, age (≥48 years old) was an independent risk factor for mortality as well.\n\n\nDiscussion\n\nTo the best of our knowledge, our study is the first comprehensive, decently sized study addressing the potential association between anemia and clinical outcomes in hospitalized COVID-19 patients in the United Arab Emirates. These outcomes included disease severity, risk of ICU admission, and mortality. Additionally, the study explored possible correlation between certain demographic variables and the disease outcomes. Based on the data collected from 3092 hospitalized adult patients in one of the largest hospitals in UAE, majority of the patients were males, 11.7% of whom were anemic. Compared to findings of previous studies, our findings indicated lower prevalence of anemia in the studied sample (11.4%), whereas other studies reported a higher prevalence of anemia ranging from 24.7%-35.5% among hospitalized COVID-19 patients.6,11 This could be explained by the predominance of males and young age (<48 years old) patients, who are considered to be at lower risk of suffering from anemia.\n\nThe prevalence of anemia was higher in females. Generally, anemia is reported to be more prevalent in females and lower hemoglobin values are seen among females compared to males even in cases without anemia, which is attributed to low iron intake and reproductive issues such as menstruation, pregnancy, and lactation.19 Interestingly, studies evaluating anemia in COVID-19 patients found a higher prevalence of anemia within the male population.20,21 On the other hand, other studies found a higher prevalence of anemia within females.11,14 Of note, however, these studies failed to demonstrate a significant association between anemia and gender. This variation from the well documented fact about anemia prevalence could be attributed to the lack of distinction between the commonly encountered iron deficiency anemia and anemia of inflammation typically linked to COVID-19.\n\nOur modelling analysis showed that patients aged ≥ 48 years old had higher prevalence of anemia. This is in agreement with many previous studies that demonstrated a higher prevalence of anemia with advancing age.11,14,20,21 Interestingly, while Chen et al. demonstrated an increasing anemia prevalence with age, the prevalence then decreased at age of 80 and above years old; however, a small number of cohort was reported in that study.14 The relationship between anemia and aging could be explained by common nutritional deficiencies (iron, folate, or vitamin B12), typically encountered with elderly or anemia of chronic diseases, and sometimes due to unknown reason. This is mainly because with aging there seems to be a progressive resistance of bone marrow erythroid progenitors to erythropoietin, and a chronic subclinical pro-inflammatory state, resulting in anemia.19\n\nOur study showed that most of COVID-19 cases with anemia were associated with high serum ferritin, which is mainly attributed to the fact that ferritin levels elevate dramatically during infection or inflammation.22 This is because ferritin by itself is a key biomarker in inflammatory and pathological conditions, mainly because it leaks from damaged cells.23 Basically, males have higher ferritin levels than females throughout their adulthood in which they peak between 30 to 39 years and stay constant until their 70’s. Whereas, females have relatively low ferritin levels, beginning to rise after menopause.22 Few studies highlighted the correlation between serum ferritin levels and COVID-19 clinical characteristics and disease outcomes. Cheng et al found that ferritin levels generally varied based on COVID-19 severity and presence of comorbidities. Ferritin levels were significantly elevated in patients with COVID-19 and other comorbidities -including anemia- rather than COVID-19 alone. This could be probably due to the presence of concurrent inflammatory and pathological reactions.24 Similarly, this finding was also illustrated in a previous observational study which reported that anemia was highly prevalent among 206 hospitalized COVID-19 patients.20\n\nAlthough COVID-19 is a primary respiratory illness, it also affects multiple organs and results in systemic complications, such as thrombotic disorders and coagulopathies. Several studies reported significant elevation in D-dimer among hospitalized COVID-19 patients, reflecting the remarkable prevalence of thrombotic disorders in this population. Thus, elevation of D-dimer could be a potential biomarker of COVID-19 poor prognosis.25 A cut-off value of D-dimer has not yet been established to predict mortality in patients with COVID-19, but one study published lately in 2021 described a cut-off point of 1.5μg/ml (sensitivity 70.6%, specificity 78.4%).25 Yet only one study compared the levels of D-dimer in anemic versus non-anemic COVID-19 patients. They found that D-dimer was higher in patients with moderate/severe anemia compared to mild anemia.11 This is in line with our findings that D-dimer levels were higher in the anemic patients’ group (p<0.001). There is a lack of clear justification behind the additional elevation of D-dimer among COVID-19 anemic cases, and further studies are required to understand this finding manifestly.\n\nThe present study reported that majority of COVID-19 patients were asymptomatic or had mild symptoms of COVID-19. However, patients with moderate or severe symptoms presented mainly with cough and fever. Likewise, a systematic review of 152 studies indicated that fever and cough were highly prevalent among COVID-19 patients.26 However, some reports revealed that in addition to cough and fever, a sudden loss of smell or taste is a common manifestation of the disease.27,28\n\nAn interesting finding of this study was the significant association between anemia and the risk of developing moderate to severe symptoms. This finding is in agreement with previously published studies that found a significant effect of anemia on disease severity related to the severe inflammatory response.11,29 Additionally, several studies that explored the parameters of developing severe disease outcomes failed to demonstrate this association with a considerable sample size.15–17 Fan (2020) investigated 69 patients and found that lymphopenia and elevated LDH were associated with higher rates of ICU admissions.15 In addition, Henry et al pooled data into a meta-analysis from 21 studies with small sample sizes; 18 studies of which inspected the severity, and the other 3 assessed the mortality rate of COVID-19 by studying several hematological parameters. Although this analysis reported a significant decline in hemoglobin levels among patients with a severe form of the disease, it did not assess anemia as a determinant factor of COVID-19 severity.16\n\nBesides, findings of this study showed almost 3-fold increase in the risk of ICU admission in COVID-19 patients with anemia compared to their counterparts. This was further proven by the results of a multivariable logistic regression after adjustment for covariates. Our results concurred with a prospective study conducted in the Middle East with a decently sized cohort (n=1274), which supports our finding that anemia is an independent risk factor for ICU admission among patients with COVID-19 (p<0.001).21 On the other hand, Cai et al. investigated factors associated with ICU admission and failed to find an association between hemoglobin levels and risk of being admitted to the ICU.30 Such results could be attributed to the small sample size of the study (n=96). In the same manner, Bellman-Weiler et al. found no significant relationship between anemia and ICU admission, but concluded that alterations in iron homeostasis -as a higher ferritin/transferrin ratio- reflected further risk of advanced disease and predicted the need for ICU admission.6 However, these findings were limited to those without iron metabolism variability, which resulted in a selection bias and a smaller sample included in the multivariate analysis. Moreover, according to Bellman-Weiler et al. hemoglobin -as a variable- was not a significant predictor in their multivariate regression analysis, illustrating a probable residual confounding for anemia classification. Furthermore, similar studies recognized the relationship between the presence of anemia and high mortality rate amongst ICU-admitted COVID-19 patients. However, these studies either did not assess ICU admission as a final outcome due to the rapid turnover (discharge or death)8,20 nor tested if the presence of anemia had an effect on admission to the ICU.29,31\n\nAccording to findings of the current study, anemia was associated with a high mortality rate among hospitalized COVID-19 patients compared to non-anemic cases with COVID-19. This observation was further reaffirmed using a multivariable logistic regression analysis, after adjusting for covariables that could contribute to this finding. The results of this study showed that anemia was an independent predictive risk factor for death in COVID-19 patients. Similarly, most studies investigated the relationship between anemia and mortality in COVID-19 patients, and all of them came to the agreement that anemia significantly contributes to a higher mortality rate. Correspondingly, a single center retrospective study assessed the impact of anemia on mortality rate among 333 hospitalized COVID-19 patients with anemia. The study has found that more than half of these patients were significantly at high risk of all-cause mortality. Moreover, AbuRuz, S et al, Bellman et al., Algassim et al, Dinevari et al, Tremblay et al, and Oh et al. showed similar results and further confirmed this association.6,12,21,31,32 In addition, Bellman et al further analyzed this association and compared the mortality rate between mild and moderate/severe anemia. Accordingly, only moderate/severe anemia was significantly associated with a higher mortality rate. Furthermore, their study examined this association after stratifying the subjects by anemia type, as anemia of functional iron deficiency vs. anemia of inflammation. They concluded that anemia of iron deficiency was not associated with higher mortality rates compared to non-anemic cases.6 On the other hand, Tremblay et al. reported that even mild anemia is a predictive risk factor of COVID 19 mortality.12\n\nConsidering other factors, multivariable regression analysis revealed that male gender, older age (≥48-year-old), significantly increased the severity of COVID-19 and ICU admissions. However, only older age was found to be an independent risk factor in addition to anemia for mortality. Previous studies evaluating the clinical impact of anemia did not evaluate the impact of demographics on the disease outcomes, rather they outlined the relationship between demographic factors and anemia.19 Available studies simply reported the prevalence of anemia in each demographic group, and tested if a significant difference was observed.21\n\nOur study is the first study in the Gulf region that spotted the light on the association between anemia and COVID-19 outcomes in terms of severity, ICU admission and mortality. We included a large sample size of COVID-19 patients in a hospital that was specialized for COVID-19 cases. We studied the association between anemia and COVID-19 severity, ICU admission and mortality by conducting a multivariable regression analysis with adjustment of certain covariables that could affect the association. Another point that highlighted the novelty of our study was that we considered other demographic factors and we tested their impact on disease severity, mortality and ICU admission using a multivariable model analysis. In addition, we measured several hematological parameters including hemoglobin, hematocrit, D-dimer and ferritin which reflected the level and significance of anemia in COVID-19 patients. Finally, our population included patients at younger ages compared to previously presented studies, making the influence of age and other comorbidities on the results less significant, since not all of the patients were elderly.\n\nThe present study had several limitations. First, this was a retrospective observational study; therefore, we were unable to accurately control exposure factors, covariates, and potential confounders. Second, it was a single center study, hence, it would be difficult for the results to be emphasized and generalized amongst other areas in the region. Third, our data were not longitudinal; we had no information about hemoglobin levels before infection and we were unable to track the changes in hematological parameters during hospitalization. Fourth, we did not collect and analyze the clinical interventions and therapeutic information related to anemia in COVID-19 patients. These data could have provided a valuable justification for the normalization of hemoglobin and hematocrit levels among patients. Lastly, we did not classify and clearly define anemia based on severity, and the etiology of anemia was not distinguished, whether it is a functional iron deficiency or anemia of inflammation. This limited our interpretations and affected the causal association between anemia and COVID-19 outcomes.\n\n\nConclusion\n\nAnemia was a common clinical manifestation among COVID-19 patients. This study highlighted the association between anemia and COVID-19 clinical outcomes. Analysis of several hematological parameters illustrated that anemia was an independent predictive factor for poor COVID-19 outcomes. Other demographic factors, such as age and gender had an impact on the clinical outcomes in COVID-19 patients. These results could be a guidance for clinicians in triaging hospitalized COVID-19 patients upon admission by considering their clinical parameters, particularly, hemoglobin levels. In turn, this could enhance the healthcare team’ decision for early, intensive therapeutic interventions for certain patient and tailor a patient-specific treatment plan. Further studies with more comprehensive follow-up of COVID-19 patients with anemia, stringent designs and encompassing multiple centers are needed to confirm causality and support generalizability and possibly develop a guideline for management of anemia in COVID-19 patients. This association should also be considered in other infectious diseases.\n\n\nAuthor contribution\n\nSham ZainAlAbdin: Conceptualization, Formal Analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing\n\nSalahdein AbuRuz: Conceptualization, Formal Analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing, Supervision\n\nAmal Akour: Conceptualization, Formal Analysis, Methodology, Writing – original draft, Writing – review & editing,\n\nRami Beiram: Conceptualization, Methodology, Writing – original draft, Writing – review & editing\n\nMunther Alnajjar: Conceptualization, Methodology, Writing – original draft, Writing – review & editing\n\nDerar Abdel-Qader: Conceptualization, Methodology, Writing – original draft, Writing – review & editing\n\nMosab Arafat: Conceptualization, Methodology, Writing – original draft, Writing – review & editing\n\nanan jarab: Conceptualization, Methodology, Writing – original draft, Writing – review & editing\n\nMohammed Aburuz: Data Curation, Writing – Original Draft Preparation, Writing – Review & Editing\n\nSara AlAshram: Conceptualization, Methodology, Writing – original draft, Writing – review & editing, Data curation\n\nSara AlJabi: Conceptualization, Methodology, Writing – original draft, Writing – review & editing, Data curation\n\nFatima AlSalama: Conceptualization, Methodology, Writing – original draft, Writing – review & editing, Data curation\n\nMohammed Al Hajjar: Conceptualization, Methodology, Writing – original draft, Writing – review & editing, Data curation",
"appendix": "Data availability statement\n\nFigshare: Could anemia impact the severity of infections? COVID-19 as an example. https://doi.org/10.6084/m9.figshare.24511999.v1\n\nThe project contains the following underlying data:\n\n• Covid anemia.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nRepository: STROBE checklist for ‘Could anemia impact the severity of infections? COVID-19 as an example”. https://doi.org/10.5281/zenodo.10907120\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\nWorld Health Organization: Worldwide prevalence of anaemia 1993-2005: WHO global database on anaemia. World Health Organization; 2008.\n\nWorld Health Organization: Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. World Health Organization; 2011.\n\nYu P, Zhu J, Zhang Z, et al.: A Familial Cluster of Infection Associated With the 2019 Novel Coronavirus Indicating Possible Person-to-Person Transmission During the Incubation Period. J. Infect. Dis. 2020; 221(11): 1757–1761. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organization: Weekly epidemiological update on COVID-19-22 March 2023.2023.\n\nShiehzadegan S, Alaghemand N, Fox M, et al.: Analysis of the Delta Variant B.1.617.2 COVID-19. Clin. Pract. 2021; 11(4): 778–784. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBellmann-Weiler R, Lanser L, Barket R, et al.: Prevalence and Predictive Value of Anemia and Dysregulated Iron Homeostasis in Patients with COVID-19 Infection. J. Clin. Med. 2020; 9(8): E2429. Publisher Full Text\n\nBi Q, Wu Y, Mei S, et al.: Epidemiology and transmission of COVID-19 in 391 cases and 1286 of their close contacts in Shenzhen, China: a retrospective cohort study. Lancet Infect. Dis. 2020; 20(8): 911–919. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOh SM, Skendelas JP, Macdonald E, et al.: On-admission anemia predicts mortality in COVID-19 patients: A single center, retrospective cohort study. Am. J. Emerg. Med. 2021; 48: 140–147. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMao J, Dai R, Du R-C, et al.: Hematologic changes predict clinical outcome in recovered patients with COVID-19. Ann. Hematol. 2021; 100(3): 675–689. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRaman N, Kv P, Ashta KK, et al.: Ferritin and Hemoglobin as Predictors of Fatal Outcome in COVID-19: Two Sides of the Same Coin. J. Assoc. Physicians India. 2021; 69(8): 11–12. PubMed Abstract\n\nTao Z, Xu J, Chen W, et al.: Anemia is associated with severe illness in COVID-19: A retrospective cohort study. J. Med. Virol. 2021; 93(3): 1478–1488. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTremblay D, Rapp JL, Alpert N, et al.: Mild anemia as a single independent predictor of mortality in patients with COVID-19. eJHaem. 2021; 2(3): 319–326. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBazick HS, Chang D, Mahadevappa K, et al.: Red Cell Distribution Width and all cause mortality in critically ill patients. Crit. Care Med. 2011; 39(8): 1913–1921. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen C, Zhou W, Fan W, et al.: Association of anemia and COVID-19 in hospitalized patients. Future Virol. 2021; 16(7): 459–466. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFan BE: Hematologic parameters in patients with COVID-19 infection: a reply. Am. J. Hematol. 2020; 95(8): E215. PubMed Abstract | Publisher Full Text\n\nHenry BM, de Oliveira MHS , Benoit S, et al.: Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin. Chem. Lab. Med. CCLM. 2020; 58(7): 1021–1028. PubMed Abstract | Publisher Full Text\n\nHuang C, Wang Y, Li X, et al.: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395(10223): 497–506. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNIH: Overview of COVID-19. 2021. Accessed 5 Dec 2022. Reference Source\n\nCappellini MD, Motta I: Anemia in Clinical Practice-Definition and Classification: Does Hemoglobin Change With Aging? Semin. Hematol. 2015; 52(4): 261–269. PubMed Abstract | Publisher Full Text\n\nBergamaschi G, Borrelli de Andreis F, Aronico N, et al.: Anemia in patients with Covid-19: pathogenesis and clinical significance. Clin. Exp. Med. 2021; 21(2): 239–246. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFaghih Dinevari M, Somi MH, Sadeghi Majd E, et al.: Anemia predicts poor outcomes of COVID-19 in hospitalized patients: a prospective study in Iran. BMC Infect. Dis. 2021; 21(1): 170. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organization: Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. Geneva: World Health Organization; 2011.\n\nKernan KF, Carcillo JA: Hyperferritinemia and inflammation. Int. Immunol. 2017; 29(9): 401–409. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCheng L, Li H, Li L, et al.: Ferritin in the coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. J. Clin. Lab. Anal. 2020; 34(10): e23618. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPoudel A, Poudel Y, Adhikari A, et al.: D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS One. 2021; 16(8): e0256744. PubMed Abstract | Publisher Full Text | Free Full Text\n\nda Rosa MR , Francelino Silva Junior LC, Santos Santana FM, et al.: Clinical manifestations of COVID-19 in the general population: systematic review. Wien. Klin. Wochenschr. 2021; 133(7): 377–382.\n\nJotz GP, Voegels RL, Bento RF: Otorhinolaryngologists and coronavirus disease 2019 (COVID-19). SciELO Brasil; 2020.\n\nKosugi EM, Lavinsky J, Romano FR, et al.: Incomplete and late recovery of sudden olfactory dysfunction in COVID-19. Braz. J. Otorhinolaryngol. 2020; 86: 490–496. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTaneri PE, Gómez-Ochoa SA, Llanaj E, et al.: Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis. Eur. J. Epidemiol. 2020; 35(8): 763–773. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCai S-H, Liao W, Chen S-W, et al.: Association between obesity and clinical prognosis in patients infected with SARS-CoV-2. Infect. Dis. Poverty. 2020; 9(1): 80. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlgassim AA, Elghazaly AA, Alnahdi AS, et al.: Prognostic significance of hemoglobin level and autoimmune hemolytic anemia in SARS-CoV-2 infection. Ann. Hematol. 2021; 100(1): 37–43. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAbuRuz S, Al-Azayzih A, ZainAlAbdin S, et al.: Clinical characteristics and risk factors for mortality among COVID-19 hospitalized patients in UAE: Does ethnic origin have an impact. PLoS One. 2022; 17(3): e0264547. PubMed Abstract | Publisher Full Text | Free Full Text"
}
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[
{
"id": "272010",
"date": "24 May 2024",
"name": "Joan-Lluis Vives-Corrons",
"expertise": [
"Reviewer Expertise Rare Anemias"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript provides valuable insights into the association between anemia and COVID-19 outcomes, supported by a large and well-characterized patient cohort. However, the limitations inherent in its retrospective, single-center design, and the lack of longitudinal and interventional data, suggest that further research is needed to confirm these findings and expand upon them. Future studies should aim for a prospective, multi-center approach, include longitudinal data, and consider the etiology of anemia to provide a more comprehensive understanding of this important health issue. Comments: 1. The retrospective observational design limits the ability to control for all possible confounding variables and to establish a causal relationship. Prospective studies or randomized controlled trials would provide stronger evidence 2. The study is conducted in a single center, which may limit the generalizability of the findings to other regions or healthcare settings. Multi-center studies would be more representative and enhance the external validity 3.The study does not track changes in hematological parameters over time during hospitalization. Longitudinal data would provide insights into the dynamics of anemia and its potential evolution in response to COVID-19. 4. The manuscript does not detail the clinical interventions and treatments related to anemia, which could influence patient outcomes. Understanding how anemia was managed during hospitalization would add depth to the analysis 5. The study does not differentiate between types of anemia (e.g., iron deficiency vs. anemia of inflammation). This distinction could impact the interpretation of the findings, as different types of anemia might have different effects on COVID-19 outcomes 6. While the study includes a diverse population in terms of gender and age, it does not address potential ethnic or socioeconomic factors that could influence both the prevalence of anemia and COVID-19 outcomes.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nI cannot comment. A qualified statistician is required.\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12735",
"date": "07 Nov 2024",
"name": "salahdein aburuz",
"role": "Author Response",
"response": "We truly appreciate the time and efforts you dedicated to reviewing our research work. Please note that all of your valuable comments have been addressed, and changes have been made in the manuscript accordingly. Many thanks 1. The retrospective observational design limits the ability to control for all possible confounding variables and to establish a causal relationship. Prospective studies or randomized controlled trials would provide stronger evidence Noted. This has been discussed in the limitations of the study, as the authors were unable to conduct this research prospectively since the pandemic was an emergency crisis for all COVID-19 patients as well as healthcare providers. 2. The study is conducted in a single center, which may limit the generalizability of the findings to other regions or healthcare settings. Multi-center studies would be more representative and enhance the external validity. Noted. Since all COVID-19 patients that were included in this study were admitted to the ICU, it was a challenge that limited healthcare facilities treated such patients in the area, and all patients were sent to one center at the beginning of the crisis. We have also included this in the study limitation section. 3.The study does not track changes in hematological parameters over time during hospitalization. Longitudinal data would provide insights into the dynamics of anemia and its potential evolution in response to COVID-19. Noted. This has been discussed in the limitations of the study, as the authors were unable to conduct this research prospectively since the pandemic was an emergency crisis for all COVID-19 patients as well as healthcare providers. Additionally, Hospital stay wasn’t long enough to track changes. On the other hand, our goal was to see the impact of admission anemia on clinical outcomes. 4. The manuscript does not detail the clinical interventions and treatments related to anemia, which could influence patient outcomes. Understanding how anemia was managed during hospitalization would add depth to the analysis. During hospitalization, the treatment focused on the management of COVID-19, anemic patients were referred to specialists/consultants for further workup after their discharge. In case of severe anemia (HG <7), patients have received blood transfusions as per the guidelines, however, this information was not part of the data collection. 5. The study does not differentiate between types of anemia (e.g., iron deficiency vs. anemia of inflammation). This distinction could impact the interpretation of the findings, as different types of anemia might have different effects on COVID-19 outcomes Noted. It was hard to differentiate the types of anemia as some patients may originally have had iron deficiency anemia and the condition worsened after the COVID-19 infection. 6. While the study includes a diverse population in terms of gender and age, it does not address potential ethnic or socioeconomic factors that could influence both the prevalence of anemia and COVID-19 outcomes. This was the aim that has been discussed in another previously published study. It is also cited in this paper the discussion, Reference number 32. AbuRuz S, Al-Azayzih A, ZainAlAbdin S, et al.: Clinical characteristics and risk factors for mortality among COVID-19 hospitalized patients in UAE: Does ethnic origin have an impact. PLoS One. 2022;17(3):e0264547. 35235580 10.1371/journal.pone.0264547 PMC8890645"
}
]
},
{
"id": "280551",
"date": "09 Jul 2024",
"name": "John McDonnell",
"expertise": [
"Reviewer Expertise immunology",
"statistical 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\nThis is an interesting study about the role of anemia in COVID-19 infection. It is overall well-written and scientifically important, but there are many small wording issues that if corrected will greatly enhance its clarity and readability.\nAdditionally, there are a few more substantial statistical issues to consider. Because these affect the science behind the paper, I believe that they are very important for the authors to consider and address, even more so than the minor quibbles I list below about wording and grammar. Therefore, I have put these in bold.\nThe most substantial statistical issue I have relates to the results section, where table 3 is referenced.\nAuthor List:\n- The name \"anan jarab\" is not capitalized. - Recommendation: Ensure consistent capitalization in the author list, e.g., \"Anan Jarab”, unless there is a specific reason not to.\nAbstract: Background:\n- The sentence \"This is the first study UAE aimed to assess the influence of anemia on COVID-19 severity, ICU admission, and mortality rate.\" is unclear. - Recommendation: Revise to \"This is the first study from the UAE aimed to assess the influence of anemia on COVID-19 severity, ICU admission, and mortality rate.\"\nMethods: - The term \"retro-prospective chart review\" is confusing. - Recommendation: Use \"retrospective chart review\" for clarity.\nIntroduction: - this is a run-on sentence and is hard to understand - \"According to the National Emergency Crisis and Disasters Management Authority (NCEMA), more than 700 thousand cases were confirmed, and 2135 deaths were reported in the United Arab Emirates (UAE) until November, 4th 2021 and the rate of developing new cases has increased to 67.0% by 2023 although majority of the people are vaccinated against COVID-19.\"\n- Recommendation: Break this into two sentences for clarity: \"According to the National Emergency Crisis and Disasters Management Authority (NCEMA), more than 700 thousand cases were confirmed, and 2135 deaths were reported in the United Arab Emirates (UAE) until November 4th, 2021. The rate of new cases increased by 67.0% by 2023, despite the majority of the population being vaccinated against COVID-19.\"\n-This seems to be the wrong “basis”: \"Genetic mutations of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) resulted in the emergence of more contagious variants; hence, increasing cases on daily bases.\" - Recommendation: Correct the word \"bases\" to \"basis\": \"Genetic mutations of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) resulted in the emergence of more contagious variants, hence increasing cases on a daily basis.\"\n- There is redundant wording in this sentence: \"Moreover, studies evaluating parameters of severe outcomes failed to demonstrate truly this association in a large considerable sample size.\" - Recommendation: Simplify to avoid redundancy: \"Moreover, studies evaluating parameters of severe outcomes failed to demonstrate this association in a large sample size.\"\nEthical Considerations: - The wording here is problematic, as past and present tenses are mixed. The use of contractions is probably best avoided in a scientific paper: \"Patients’ information was kept confidential and authors didn’t have access to information that could identify individual participants during or after data collection. Study was performed in accordance with relevant guidelines and regulations. This was a retrospective review patients’ files and therefore consent form is waived and not required.\"\n- Recommendation: Revise for consistent tense and avoid contractions: \"Patients’ information was kept confidential, and the authors did not have access to information that could identify individual participants during or after data collection. The study was performed in accordance with relevant guidelines and regulations. This was a retrospective review of patients’ files; therefore, a consent form was waived and not required.\"\nData Collection: - This sentence is confusing, and the use of parentheses is incorrect: \"Baseline vital signs upon admission (heart rate, respiratory rate, oxygen saturation, systolic, and diastolic blood pressure) in addition to the most relevant laboratory parameters to anemia, such as (hemoglobin, hematocrit, ferritin, D-dimer, and alkaline phosphatase) were reviewed and analyzed.\" - Recommendation: Clarify and streamline the sentence: \"Baseline vital signs upon admission, including heart rate, respiratory rate, oxygen saturation, and systolic and diastolic blood pressure, as well as key laboratory parameters related to anemia (hemoglobin, hematocrit, ferritin, D-dimer, and alkaline phosphatase), were reviewed and analyzed.\"\nTable 2: - Issue: The row \"Male 5.0% (120/2407) 1.58 1.00-2.51 0.028\" indicates a statistically significant adjusted odds ratio (aOR) with a confidence interval that includes 1.00. This does not make sense to me, as a confidence interval that includes 1 should not be significant by definition. Please correct me if I am wrong or I am missing something about the analysis.\n- Recommendation: Verify the confidence interval and ensure that it does not include 1.00 if the result is statistically significant. If this is due to rounding, consider providing more precise values to clarify the significance.\nTable 3: - The word \"Normal\" is followed by asterisks (*) that do not point to anything elsewhere in the table or text. - Recommendation: Remove the asterisks if they are not referencing any footnotes or additional information or provide a clear explanation if they are meant to reference something.\n\n- Inconsistent use of percentages in \"Covid 19 outcomes Severity of anemia % (n/N) P-Value Moderate to Severe Disease Normal* 21.6% (590/2730) <0.001 Mild 30.3 (90/297) Moderate to Severe 29.3 (19/65)\". - Recommendation: Ensure percentages are used consistently throughout the table for clarity. For example: \"Mild 30.3% (90/297) Moderate to Severe 29.3% (19/65)\".\nResults Section (Referencing Table 3): - This sentence is problematic: \"Upon classifying patients anemia into normal, mild and moderate to severe; severity of COVID-19 was higher in anemic compared to normal patients (p <0.001). On the other hand, moderate-to-severe anemia was associated with greater ICU admissions and mortality rates (p <0.001) as presented in Table 3.\" -this is because a significant p-value indicates an overall difference in proportions among the groups as a whole (at least one of them is different, but we do not know which one) but does not specify which groups are different from each other. Which specific group is different cannot be verified without further post-hoc testing which probably should come at the cost of a statistical penalty for repeated comparisons (Bonferroni, etc). - Recommendation: Clarify that the p-value here indicates an overall difference between subgroups and suggest that further post-hoc testing, such as Tukey's HSD, would be needed to identify specific group differences. Alternately perform such post-hoc testing and put the results in the table.\nTable 4: - The confidence interval for \"Gender (male) 1.43 1.15-178 <0.001\" appears to be unusually wide. I am wondering if this was due to a typographical error. - Recommendation: Verify the correct confidence interval and revise it if necessary. For example: \"Gender (male) 1.43 1.15-1.78 <0.001\".\nDiscussion: - Clarify this sentence: \"Based on the data collected from 3092 hospitalized adult patients in one of the largest hospitals in UAE, majority of the patients were males, 11.7% of whom were anemic.\" - Recommendation: Change \"majority\" to \"the majority\": \"Based on the data collected from 3092 hospitalized adult patients in one of the largest hospitals in the UAE, the majority of the patients were males, 11.7% of whom were anemic.\"\n- Clarify this sentence: \"Interestingly, while Chen et al. demonstrated an increasing anemia prevalence with age, the prevalence then decreased at age of 80 and above years old; however, a small number of cohort was reported in that study.\" - Recommendation: Change \"a small number of cohort\" to \"a small cohort\": \"Interestingly, while Chen et al. demonstrated an increasing anemia prevalence with age, the prevalence then decreased at the age of 80 and above; however, a small cohort was reported in that study.\"\n- Clarify this sentence \"The relationship between anemia and aging could be explained by common nutritional deficiencies (iron, folate, or vitamin B12), typically encountered with elderly or anemia of chronic diseases, and sometimes due to unknown reason.\" - Recommendation: Pluralize \"reason\" to \"reasons\": \"The relationship between anemia and aging could be explained by common nutritional deficiencies (iron, folate, or vitamin B12), typically encountered in the elderly or in cases of anemia of chronic diseases, and sometimes due to unknown reasons.\"\n- The abrupt start of this sentence is confusing: \"Whereas, females have relatively low ferritin levels, beginning to rise after menopause.\" - Recommendation: Simplify and clarify: \"Females typically have relatively low ferritin levels, which begin to rise after menopause.\"\n- This sentence seems to be too strong. It is hard to say that a statistical model truly proved this: \"This was further proven by the results of a multivariable logistic regression after adjustment for covariates.\" - Recommendation: Use a more appropriate term such as \"supported\" or \"demonstrated\": \"This was further supported by the results of a multivariable logistic regression after adjustment for covariates.\"\n- Need a citation here: \"Correspondingly, a single-center retrospective study assessed the impact of anemia on mortality rate among 333 hospitalized COVID-19 patients with anemia. The study has found that more than half of these patients were significantly at high risk of all-cause mortality.\" - Recommendation: Add a citation: \"Correspondingly, a single-center retrospective study assessed the impact of anemia on mortality rate among 333 hospitalized COVID-19 patients with anemia. The study found that more than half of these patients were significantly at high risk of all-cause mortality (Citation needed).\"\n- Wording is awkward here: \"Considering other factors, multivariable regression analysis revealed that male gender, older age (≥48-year-old), significantly increased the severity of COVID-19 and ICU admissions. However, only older age was found to be an independent risk factor in addition to anemia for mortality.\"\n- Recommendation: Rework for clarity: \"Multivariable regression analysis revealed that male gender and older age (≥48 years) significantly increased the severity of COVID-19 and ICU admissions. However, only older age, along with anemia, was found to be an independent risk factor for mortality.\"\n- I know what the authors mean here, but the way this sentence is worded is technically inaccurate. Our ability to interpret an association due to limitations in study design or analytic method do not actually affect the causal association itself, merely our ability to detect it: \"This limited our interpretations and affected the causal association between anemia and COVID-19 outcomes.\"\n- Recommendation: Clarify that the limitations were a barrier to assessing causality: \"This limited our interpretations and were a barrier to assessing the causal association between anemia and COVID-19 outcomes.\"\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? 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": "12736",
"date": "05 Nov 2024",
"name": "salahdein aburuz",
"role": "Author Response",
"response": "We truly appreciate the time and efforts you dedicated to reviewing our research work. Please note that all of your valuable comments have been addressed, and changes have been made in the manuscript accordingly. Many thanks Response to comments: Author List: - The name \"anan jarab\" is not capitalized. - Recommendation: Ensure consistent capitalization in the author list, e.g., \"Anan Jarab”, unless there is a specific reason not to. Response: Modified the name to: “Anan Jarab” as recommended. Abstract: Background: - The sentence \"This is the first study UAE aimed to assess the influence of anemia on COVID-19 severity, ICU admission, and mortality rate.\" is unclear. - Recommendation: Revise to \"This is the first study from the UAE aimed to assess the influence of anemia on COVID-19 severity, ICU admission, and mortality rate.\" Response: Modified as recommended. Methods: - The term \"retro-prospective chart review\" is confusing. - Recommendation: Use \"retrospective chart review\" for clarity. Response: Modified as recommended. Introduction: - this is a run-on sentence and is hard to understand - \"According to the National Emergency Crisis and Disasters Management Authority (NCEMA), more than 700 thousand cases were confirmed, and 2135 deaths were reported in the United Arab Emirates (UAE) until November, 4th 2021 and the rate of developing new cases has increased to 67.0% by 2023 although majority of the people are vaccinated against COVID-19.\" - Recommendation: Break this into two sentences for clarity: \"According to the National Emergency Crisis and Disasters Management Authority (NCEMA), more than 700 thousand cases were confirmed, and 2135 deaths were reported in the United Arab Emirates (UAE) until November 4th, 2021. The rate of new cases increased by 67.0% by 2023, despite the majority of the population being vaccinated against COVID-19.\" Response: Modified as recommended. -This seems to be the wrong “basis”: \"Genetic mutations of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) resulted in the emergence of more contagious variants; hence, increasing cases on daily bases.\" - Recommendation: Correct the word \"bases\" to \"basis\": \"Genetic mutations of severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) resulted in the emergence of more contagious variants, hence increasing cases on a daily basis.\" Response: Modified as recommended. - There is redundant wording in this sentence: \"Moreover, studies evaluating parameters of severe outcomes failed to demonstrate truly this association in a large considerable sample size.\" - Recommendation: Simplify to avoid redundancy: \"Moreover, studies evaluating parameters of severe outcomes failed to demonstrate this association in a large sample size.\" Response: Modified as recommended. Ethical Considerations: - The wording here is problematic, as past and present tenses are mixed. The use of contractions is probably best avoided in a scientific paper: \"Patients’ information was kept confidential and authors didn’t have access to information that could identify individual participants during or after data collection. Study was performed in accordance with relevant guidelines and regulations. This was a retrospective review patients’ files and therefore consent form is waived and not required.\" - Recommendation: Revise for consistent tense and avoid contractions: \"Patients’ information was kept confidential, and the authors did not have access to information that could identify individual participants during or after data collection. The study was performed in accordance with relevant guidelines and regulations. This was a retrospective review of patients’ files; therefore, a consent form was waived and not required.\" Response: Modified as recommended. Data Collection: - This sentence is confusing, and the use of parentheses is incorrect: \"Baseline vital signs upon admission (heart rate, respiratory rate, oxygen saturation, systolic, and diastolic blood pressure) in addition to the most relevant laboratory parameters to anemia, such as (hemoglobin, hematocrit, ferritin, D-dimer, and alkaline phosphatase) were reviewed and analyzed.\" - Recommendation: Clarify and streamline the sentence: \"Baseline vital signs upon admission, including heart rate, respiratory rate, oxygen saturation, and systolic and diastolic blood pressure, as well as key laboratory parameters related to anemia (hemoglobin, hematocrit, ferritin, D-dimer, and alkaline phosphatase), were reviewed and analyzed.\" Response: Modified as recommended. Table 2: - Issue: The row \"Male 5.0% (120/2407) 1.58 1.00-2.51 0.028\" indicates a statistically significant adjusted odds ratio (aOR) with a confidence interval that includes 1.00. This does not make sense to me, as a confidence interval that includes 1 should not be significant by definition. Please correct me if I am wrong or I am missing something about the analysis. - Recommendation: Verify the confidence interval and ensure that it does not include 1.00 if the result is statistically significant. If this is due to rounding, consider providing more precise values to clarify the significance. Response: This was a system error, where all ORs were approximated to 2 decimal points. In this case, the value was 1.00095, that’s why, it was presented as 1.00. So, we have modified it to be more precise. Table 3: - The word \"Normal\" is followed by asterisks (*) that do not point to anything elsewhere in the table or text. - Recommendation: Remove the asterisks if they are not referencing any footnotes or additional information or provide a clear explanation if they are meant to reference something. Response: Removed the asterisks (*) as recommended. - Inconsistent use of percentages in \"Covid 19 outcomes Severity of anemia % (n/N) P-Value Moderate to Severe Disease Normal* 21.6% (590/2730) <0.001 Mild 30.3 (90/297) Moderate to Severe 29.3 (19/65)\". - Recommendation: Ensure percentages are used consistently throughout the table for clarity. For example: \"Mild 30.3% (90/297) Moderate to Severe 29.3% (19/65)\". Response: Percentages (%) has been modified to be consistent throughout the table as recommended. Results Section (Referencing Table 3): - This sentence is problematic: \"Upon classifying patients anemia into normal, mild and moderate to severe; severity of COVID-19 was higher in anemic compared to normal patients (p <0.001). On the other hand, moderate-to-severe anemia was associated with greater ICU admissions and mortality rates (p <0.001) as presented in Table 3.\" -this is because a significant p-value indicates an overall difference in proportions among the groups as a whole (at least one of them is different, but we do not know which one) but does not specify which groups are different from each other. Which specific group is different cannot be verified without further post-hoc testing which probably should come at the cost of a statistical penalty for repeated comparisons (Bonferroni, etc). - Recommendation: Clarify that the p-value here indicates an overall difference between subgroups and suggest that further post-hoc testing, such as Tukey's HSD, would be needed to identify specific group differences. Alternately perform such post-hoc testing and put the results in the table. Response: Modified as recommended. Table 4: - The confidence interval for \"Gender (male) 1.43 1.15-178 <0.001\" appears to be unusually wide. I am wondering if this was due to a typographical error. - Recommendation: Verify the correct confidence interval and revise it if necessary. For example: \"Gender (male) 1.43 1.15-1.78 <0.001\". Response: Corrected as recommended. Discussion: - Clarify this sentence: \"Based on the data collected from 3092 hospitalized adult patients in one of the largest hospitals in UAE, majority of the patients were males, 11.7% of whom were anemic.\" - Recommendation: Change \"majority\" to \"the majority\": \"Based on the data collected from 3092 hospitalized adult patients in one of the largest hospitals in the UAE, the majority of the patients were males, 11.7% of whom were anemic.\" Response: Modified as recommended. - Clarify this sentence: \"Interestingly, while Chen et al. demonstrated an increasing anemia prevalence with age, the prevalence then decreased at age of 80 and above years old; however, a small number of cohort was reported in that study.\" - Recommendation: Change \"a small number of cohort\" to \"a small cohort\": \"Interestingly, while Chen et al. demonstrated an increasing anemia prevalence with age, the prevalence then decreased at the age of 80 and above; however, a small cohort was reported in that study.\" Response: Modified as recommended. - Clarify this sentence \"The relationship between anemia and aging could be explained by common nutritional deficiencies (iron, folate, or vitamin B12), typically encountered with elderly or anemia of chronic diseases, and sometimes due to unknown reason.\" - Recommendation: Pluralize \"reason\" to \"reasons\": \"The relationship between anemia and aging could be explained by common nutritional deficiencies (iron, folate, or vitamin B12), typically encountered in the elderly or in cases of anemia of chronic diseases, and sometimes due to unknown reasons.\" Response: Modified as recommended. - The abrupt start of this sentence is confusing: \"Whereas, females have relatively low ferritin levels, beginning to rise after menopause.\" - Recommendation: Simplify and clarify: \"Females typically have relatively low ferritin levels, which begin to rise after menopause.\" Response: Modified as recommended. - This sentence seems to be too strong. It is hard to say that a statistical model truly proved this: \"This was further proven by the results of a multivariable logistic regression after adjustment for covariates.\" - Recommendation: Use a more appropriate term such as \"supported\" or \"demonstrated\": \"This was further supported by the results of a multivariable logistic regression after adjustment for covariates.\" Response: Modified “proven” to “supported” as recommended. - Need a citation here: \"Correspondingly, a single-center retrospective study assessed the impact of anemia on mortality rate among 333 hospitalized COVID-19 patients with anemia. The study has found that more than half of these patients were significantly at high risk of all-cause mortality.\" - Recommendation: Add a citation: \"Correspondingly, a single-center retrospective study assessed the impact of anemia on mortality rate among 333 hospitalized COVID-19 patients with anemia. The study found that more than half of these patients were significantly at high risk of all-cause mortality (Citation needed).\" Response: Added citation number “8” for \"Correspondingly, a single-center retrospective study assessed the impact of anemia on mortality rate among 333 hospitalized COVID-19 patients with anemia. The study found that more than half of these patients were significantly at high risk of all-cause mortality (Citation needed).\" - Wording is awkward here: \"Considering other factors, multivariable regression analysis revealed that male gender, older age (≥48-year-old), significantly increased the severity of COVID-19 and ICU admissions. However, only older age was found to be an independent risk factor in addition to anemia for mortality.\" - Recommendation: Rework for clarity: \"Multivariable regression analysis revealed that male gender and older age (≥48 years) significantly increased the severity of COVID-19 and ICU admissions. However, only older age, along with anemia, was found to be an independent risk factor for mortality.\" Response: Modified as recommended. - I know what the authors mean here, but the way this sentence is worded is technically inaccurate. Our ability to interpret an association due to limitations in study design or analytic method do not actually affect the causal association itself, merely our ability to detect it: \"This limited our interpretations and affected the causal association between anemia and COVID-19 outcomes.\" - Recommendation: Clarify that the limitations were a barrier to assessing causality: \"This limited our interpretations and was a barrier to assessing the causal association between anemia and COVID-19 outcomes.\" Response: Modified as recommended."
}
]
}
] | 1
|
https://f1000research.com/articles/13-295
|
https://f1000research.com/articles/12-247/v1
|
06 Mar 23
|
{
"type": "Method Article",
"title": "Recognizing human activities using light-weight and effective machine learning methodologies",
"authors": [
"Keerthi Varadhi",
"Chinta Someswara Rao",
"GNVG Sirisha",
"Butchi Raju katari",
"GNVG Sirisha"
],
"abstract": "Background\nHuman activity recognition is a dynamic and challenging task. It is a large field of research and development. It involves predicting the movement of a person from the raw sensor data using a machine learning model. To accurately detect human activities for e-health systems, several research attempts have been carried out using data mining and machine learning techniques, but there still is room to improve the performance. To this aim, human activities such as walking, standing, laying, sitting, walking upstairs, walking downstairs are predicted using prominent machine learning models. The aim of human activity recognition is examining actions from photos or video clips. This serves as the driving force behind human activity identification systems' aim to accurately classify input data into the relevant activity category. Methods\nSix machine learning techniques, including decision tree, random forest, linear regression, Naïve bayes, k-nearest neighbour, and neural networks algorithms, were used for human activity recognition. Results\nThe performance of decision tree, random forest, linear regression, Naïve bayes, k-nearest neighbor, and neural network algorithms was assessed with a human activity recognition dataset. From the results, the random forest classifier and neural network gave good results, whereas the Naïve bayes result was not satisfying. Conclusions We classified the SITTING, STANDING, LAYING, WALKING, WALKING_DOWNSTAIRS, WALKING_UPSTAIRS activities with machine learning techniques with 98% of accuracy",
"keywords": [
"Classification",
"Land Cover",
"Deep Learning",
"CNN"
],
"content": "Introduction\n\nThe task of recognizing the present physical action done by one or more users from a series of observations is known as human activity recognition. These observations are made while the user is doing any action in the defined environment. The rise of omnipresent, wearable, and persuasive computing has spawned a variety of new uses. Human activity recognition has evolved into a significant technology that is altering people's everyday routines. The notion of human activity recognition has recently gained popularity, resulting in a variety of applications such as assistive technology, health and fitness tracking, elder care, and automated surveillance. Furthermore, activity recognition research has progressed at such a quick pace that it is already being used for purposes other than activity recognition like monitoring elderly people or prison inmates.\n\nMobile phone sensors play an important part in making smart phones more useful and aware of their surroundings such as space, the presence of lamp, rubbish, among others. As a result, most smart phones have a variety of integrated sensors. It is feasible to get a large quantity of information on a person's everyday life and activities using this method. Among these sensor devices are accelerometer and gyroscope sensors. We can capture the motion of an item with the right usage of these sensors. As a result, machine learning algorithms may be used to anticipate human action based on sensor data. The information is constantly monitored. Human activity recognition is capable of identifying a variety of actions, both basic and complicated.\n\nSome of the literature papers on human activity recognition are included in this section. The details are depicted in Table 1.\n\n\nMethods\n\nThe methodology for human activity recognition comprises four phases: input, data cleaning, data splitting, and classification and validation. Human activity recognition structure is shown in Figure 1.\n\nInput: The dataset downloaded from the UCI dataset repository was the input of our study. The dataset contained information about triaxial acceleration from an accelerometer and triaxial angular velocity from a gyroscope. The dataset contains totally 10,299 data entries and 561 features.\n\nData cleaning: Data cleaning means removing the unnecessary columns and removing or replacing the inaccurate records from the dataset. In data cleaning, an encoding technique is applied to convert categorical data into numerical data. In our dataset, all feature values were numerical, hence there was no need to apply an encoding technique. Data cleaning prevents an error from happening again.\n\nThe first step in data cleaning is removing unwanted observations from the dataset. These unwanted data include irrelevant and duplicate data. Duplicate data most frequently arises when we combine data from multiple resources; irrelevant data refers to data that do not fit to the problem.\n\nThe second step is to handle the missing data. This can be done in two ways:\n\n- Removing the record\n\n- Filling the missing values based on other observations\n\nRemoving the record and filling the missing value manually were not fully optimal because we were losing some information; for example, range might be replaced with another value. Hence, for missing numerical data we had to take the following two steps:\n\n- Flag the observation with an indicator value of missingness\n\n- Fill the observation with 0 just to ensure that there are no missing value\n\nBy using the technique of flagging and filling, the algorithm can estimate the missing value optimally.\n\nData splitting: In this phase the data is segmented into two components\n\n- Training data\n\n- Testing data\n\nTraining data: The data which was used to train the model. We took 60% of the data as the training data.\n\nTesting data: The data which was used to test our model is called testing data. We have taken 20% of the data from the dataset as testing data.\n\nClassification and validation: The classification and validation was further comprised of two phases\n\n- Classification algorithms\n\n- Evaluation metrics\n\nClassification: Classification is the process predicting the target class of new observation based on the training data. The dataset we selected contains the target class hence we implemented the model using classification algorithms. We used the following algorithms\n\n▪ Naïve Bayes13\n\n▪ K-nearest neigbours14\n\n▪ Decision tree15\n\n▪ Random forest16\n\n▪ Simple logistic regression17\n\n▪ Neural network18\n\nDecision tree: This classification uses tree representation to solve a problem. Each internal node represents the features, branches represent the outcome of the feature and leaf node represent target class labels.\n\n\n\n1. Identify the best attribute and make it as root.\n\n2. Subdivide the training set into sections.\n\n3. Repeat the previous two stages until all of the tree's branches have leaf nodes.\n\nAttribute selection measures: We had to select the best attribute for node at each level. This can be done by two measures\n\n- Information gain\n\n- Gini Index\n\nInformation gain is mathematically defined as Equation 1\n\nHence from entropy, information gain is mathematically represented as\n\nGini index: It measures how often a randomly chosen element would be incorrectly classified.\n\nAs our dataset were unbalanced, meaning there were multiple classes, a decision tree made use of information gain to select the best attribute.\n\nLogistic regression: Logistic regression is a statistical method used for classification which falls under supervised learning. It is used for predictions based on probability concepts. It analyses data set and take discrete independent input values and give a single output.\n\nLogistic function: Logistic function is also known as the sigmoid function, which takes a real-value number as input and maps it into a value between 0 and 1, but not exactly at those limits. It maps predictions to probabilities.\n\nBy using the sigmoid function, if we give an input value on x, then it predicts the target value on the y axis.\n\nHere k = 1, x0=0,L=1\n\n\n\n1. Plot the labelled data\n\n2. Draw the regression curve\n\n3. Find out the best fitted curve using maximum likelihood estimator (MLE)\n\n▪ Convert y-axis probability scale to log (odds)\n\n▪ Assume regression line and scale paper data to regression line\n\n▪ Apply sigmoid function\n\nNaïve Bayes classifier: Naïve is a probabilistic classification algorithm which is based on Bayes theorem. It assumes that the occurrence of an instance is independent of other instances.\n\nThe conditional probability of an object with feature vector x1,x2,… …., xn belongs to a particular class Ci, and it is calculated with Equation 7.\n\n\n\n1. The data set is used to construct a frequency table.\n\n2. By computing the probabilities of all the elements in the dataset, a likelihood table is constructed.\n\n3. Posterior probability is calculated for each class by using (1).\n\n4. The class with the highest posterior probability is the output.\n\nGaussian naïve Bayes: As values of each feature of our data set are continuous, we use the Gaussian distribution, which is also called the normal distribution.\n\nWhere μ is the mean of all the values a feature and σis the standard deviation.\n\nK-nearest neighbours is one of the essential classification algorithms. It falls under the category of supervised learning. It assumes that similar data are close to each other. Here the data is classified into groups based on an attribute. It is used in applications like pattern recognition, intrusion detection and data mining.\n\nLet N be the number of training samples of data and U is the unknown point.\n\nThe data set is stored in an array each element represented as a tuple (x, y).\n\nFor i = 0 to n-1\n\nBegin\n\nEuclidian distance from each point to U is calculated.\n\nS is the set of m smallest distances (all the points related to distances must be classified)\n\nend\n\nReturn (Mode (m labels))\n\nRandom forest: Random forests are ensembles, which means combination of two or more models to get better results. Random forests create a forest of decision trees on data samples. Each decision tree gives a target class as output and the final target class is identified by performing some measures on outputs from each decision tree of corresponding input record.\n\n\n\n1. Picks random samples from the provided dataset.\n\n2. For each random sample, creates a decision tree.\n\n3. Predicts the result from every decision tree.\n\n4. Predicts target class of sample by simple voting as the final result.\n\nArtificial neural network (ANN): ANN are made up of nodes that are connected to one other. The values of the property are stored in these nodes. The input values for ANN are collected from the training example's characteristics. The weighted values are subsequently delivered to the next set of nodes. This weighted total is subjected to a non-linear activation function, and the resulting value is transmitted to the next layer, where the process is repeated until the final output is reached. Figure 2 depicts this process.\n\nBy adjusting the weights in ANN, the anticipated output value gets closer to the observed value. The back-propagation algorithm is the most often used method for altering weights. The complete training set is applied repeatedly due to the nature of ANN learning, where each application is unique.\n\nValidation: Evaluation metrics were used to verify how well the model fits to our data. There are many metrics to evaluate the model; some of the measures are accuracy, precision, recall, F1 score.\n\nPrecision: Precision is also known as positive predicted value which is a measure of accuracy. It is mathematically defined as true positives divided by the sum of true positives and false positives.\n\nRecall: Recall is also referred toas sensitivity, which is a measure of accuracy. It is mathematically defined as true positives divided by sum of true positives and false negatives.\n\nF1 score: The F1 score is calculated with equation 11\n\nAccuracy: Accuracy defines how well the model predicts the class. It is mathematically defined as the number of truly predicted classes divided by total number of classes.\n\n\nResults and discussion\n\nThe Results section comprises two parts:\n\n- Exploratory data analysis results\n\nExploratory data analysis means gaining insights from the data before applying any model to it. It can be done using mathematical functions and visualizations. The total number of rows and columns in a dataset are identified by using the ‘shape’ function. It is shown in Figure 3.\n\nFrom this we know that the dataset contains 10299 instances and 562 attributes.\n\nOut of 562 attributes 561 are independent attributes and one is dependent variable.\n\nWe used graphs to explore the data. We used a bar graph, box plot and heatmap.\n\nA bar graph shows the comparison between different target classes. The bar graph showing how many persons had thesame classification is shownin Figure 4. The following observations were made from Figure 4: LAYING--1944, STANDING--1906, SITTING--1777, WALKING--1722, WALKING_UPSTAIRS--1544, WALKING_DOWNSTAIRS--1406.\n\nBox plot: Box plots show the distribution of data by using five measures, namely minimum, first quartile(Q1), median, third quartile(Q3), and maximum. The box plot is drawn for the target class ‘Activity’ and the feature ‘tBodyAcc-max()-X’ in Figure 5.\n\nFrom Figure 5, we made the following observations:\n\n- If tBodyAcc-max()-X is less than -0.75 then activities are either Standing, Sitting or Laying.\n\n- If tBodyAcc-max()-X is greater than -0.50 then activities are classified as Walking or Walking_Downstairs or Walking_Upstairs.\n\n- If tBodyAcc-max()-X is greater than 0.00 then activity is Walking_Downstairs.\n\nConfusion matrix for naïve Bayes classifier is shown in Figure 6. From Figure 6, the following observations were made:\n\n- The actual number of Laying was 389 but the model correctly predicted 361 as Laying and incorrectly predicted 22 as Sitting and nine as Walking_Upstairs.\n\n- The actual number of Sitting was 372 but the model correctly predicted 336 as Sitting and incorrectly predicted two as Laying, 31 as Standing and three as Walking_Upstairs.\n\n- The actual number of Standing was 375 but the model correctly predicted 157 as Standing, and incorrectly predicted 214 as Sitting and four as Walking_Upstairs.\n\n- Th actual number of Walking was 345 but model correctly predicted 256 as Walking and incorrectly predicted 31 as Walking_Downstairs and 58 as Walking_Upstairs.\n\n- The actual number of Walking_Downstairs was 282 but the model correctly predicted 199 of them as Walking_Downstairs and incorrectly predicted 25 as Walking and 58 as Walking_Upstairs.\n\n- The actual number of Walking_Upstairs was 297 but the model correctly predicted 275 of them as Walking_Upstairs and incorrectly predicted 17 as Walking_Downstairs and five as Walking.\n\nPrecision, recall and F1 score values of naïve Bayes classifier are depicted in the bar plot shown in Figure 7. From Figure 7, we can conclude that the class Laying was most correctly predicted among all other classes. Among all the classes, Standing had a low number of correctly predicted instances.\n\nConfusion matrix for the decision tree classifier is shown in Figure 8. From Figure 8, the following observations were made:\n\n- The actual number of Laying was 389 and the model correctly predicted 389 as Laying.\n\n- The actual number of Sitting was 372 but the model correctly predicted346 of them as Sitting and incorrectly predicted 26 as Standing.\n\n- The actual number of Standing was 375 but the model correctly predicted 347 of them as Standing and incorrectly predicted 28 as Sitting.\n\n- The actual number of Walkingwas 345 but the model correctly predicted324 as Walking and incorrectly predicted six of them as Walking_Downstairs and 15 as Walking_Upstairs.\n\n- The actual number of Walking_Downstairs was 282, but the model correctly predicted 257 of them as Walking_Downstairs and incorrectly predicted eight as Walking and 15 as Walking_Upstairs.\n\n- The actual number of Walking_Upstairs was 297, but the model correctly predicted 266 as Walking_Upstairs and incorrectly predicted13 as Walking and 18 as Walking_Downstairs.\n\nPrecision, recall and F1 score values of decision tree classifier are depicted in the bar plot shown in Figure 9. From Figure 9 we can see that the class Laying was predicted correctly without any incorrectly classified classes.\n\nConfusion matrix for K-nearest neighbours classifier is shown in Figure 10. From Figure 10, the following observations were made:\n\n- The actual number of Laying was 389 and the model correctly predicted 389 as Laying.\n\n- The actual number of Sitting was 372, but the model correctly predicted 332 of them as Sitting and incorrectly predicted 239 as Standing and one as Sitting.\n\n- The actual number of Standing was 375, but the model correctly predicted 354 as Standing and incorrectly predicted 21 as Sitting.\n\n- The actual number of Walking was 345, but the model correctly predicted 344 of them as Walking and incorrectly predicted one as Walking_Upstairs.\n\n- The actual number of Walking_Downstairs was 282, but the model correctly predicted 280 of them as Walking_Downstairs and incorrectly predicted two as Walking.\n\n- The actual number of Walking_Upstairs was 297,and the model correctly predicted all 297 as Walking_Upstairs.\n\nPrecision, recall and F1 score values of the K-nearest neighbour classifier are depicted in the bar plot shown in Figure 11. From Figure 11, we can see that the activity Laying was predicted correctly without any incorrectly classified classes; hence, all metrics had a 100% score.\n\nConfusion matrix for the random forest classifier is shown in Figure 12. From Figure 12, the following observations were made:\n\n▪ The actual number of Laying was 389 and the model correctly predicted 389 as Laying.\n\n▪ The actual number of Sitting was 372, but the model correctly predicted 355 as Sitting and incorrectly predicted 17 as Standing.\n\n▪ The actual number of Standing was 375, but the model correctly predicted 355 of them as Standing and incorrectly predicted 20 as Sitting.\n\n▪ The actual number of Walking was 345, but the model correctly predicted 336 as Walking and incorrectly predicted two as Walking_Downstairs and seven as Walking_Upstairs.\n\n▪ The actual number of Walking_Downstairs was 282, but the model correctly predicted 265 of them as Walking_Downstairs and incorrectly predicted 12 as Walking and five as Walking_Upstairs.\n\n▪ The actual number of Walking_Upstairs was 297, but the model correctly predicted 286 as Walking_Upstairsand incorrectly predicted seven as Walkingand four as Walking_Downstairs.\n\nPrecision, recall and F1 score values of random forest are depicted as a bar plot shown in Figure 13.From Figure 13 we can see that all instances having Laying as target were correctly predicted.\n\nConfusion matrix for logistic regression is shown in Figure 14. From Figure 14, the following observations were made:\n\n- The actual number of Laying was 389 and the model correctly predicted 389 as Laying.\n\n- The actual number of Sitting was 372, but the model correctly predicts 351 of them as Sitting and incorrectly predicts 21 as Standing.\n\n- The actual number of Standing was 375 but the model correctly predicted 360 of them as Standing and incorrectly predicted 15 as Sitting.\n\n- The actual number of Walkingwas 345, but the model correctly predicted 344 of them as Walking and incorrectly predicted one as Walking_Upstairs.\n\n- The actual number of Walking_Downstairs was 282, but the model correctly predicted 281 as Walking_Downstairs and incorrectly predicts one as Walking_Upstairs.\n\n- The actual number of Walking_Upstairs was 297 but the model correctly predicted295 of them as Walking_Upstairs and incorrectly predicted one as Walking and one as Walking_Downstairs.\n\nPrecision, recall and F1 score values of logistic regression are depicted as a bar plot shown in Figure 15. From Figure 15, we can see that Laying, Walking, Walking_Downstairs instances were correctly classified.\n\nNeural network: Epoch versus training loss for the human activity dataset is represented in Figure 16. From Figure 16, the testing loss decreased and hence the accuracy increased. Of all the algorithms we applied, neural networks predicted more accurately, with an accuracy of 98.93%\n\nComparison of different algorithms: Different algorithms used to train the model were considered as variable x and their corresponding accuracy as variable y. The bar graph drawn for these x and y variables is shown in Figure 17. The accuracy results are shown in Table 2. From Figure 17, when comparing all algorithms, neural network predicted the data with the highest accuracy, i.e.98.93%.\n\n\nConclusions\n\nFor this work, human activity recognition was used is to detect the activity of a person. The data set was collected by sensors from triaxial accelerometer and gyroscope. The data set consisted of 561 features and 10,299 records, and six classes, namely Sitting, Standing, Laying, Walking, Walking_Downstairs, Walking_Upstairs. In this paper we used six algorithms, namely naïve Bayes, decision tree, random forest, K-nearest neighbours and neural network. For neural networks, the input layer consisted of 561 nodes and three hidden layers (1024,512,64);output layers consisted of six nodes, each representing a target class. From the experimental results, naïve Bayes classifier achieved 76.89% accuracy, the decision tree classifier achieved 93.39%, random forest classifier achieved 96.89%; K-nearest neighbours achieved 96.40%;logistic regression classifier achieved 98.05%. Among all these models,the neural networks model predicted the target class with an accuracy of 98.93%.",
"appendix": "Data availability\n\nKaggle: Human Activity Recognition with Smartphones, https://www.kaggle.com/datasets/uciml/human-activity-recognition-with-smartphones\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\nSource code available from: https://github.com/someshchinta/Human_Actiity_recognition\n\nArchived source code at time of publication: https://doi.org/10.5281/zenodo.7108706\n\nLicense: Apache-2.0\n\n\nReferences\n\nSchüldt IL, Caputo B: Recognizing human actions: a local SVM approach. Pattern Proceedings of the 17th International Conference on Pattern Recognition. 2004; vol. 23: pp. 32–36. Cambridge, UK.\n\nLaptev I, Marszalek M, Schmid C, et al.: Learning realistic human actions from movies. 2008 IEEE Conference on Computer Vision and Pattern Recognition. 2008; vol. 4: pp. 1–8. Anchorage, AK, USA.\n\nYamato J, Ohya J, Ishii K: Recognizing human action in time-sequential images using hidden markov model. Proceedings 1992 IEEE Computer Society Conference on Computer Vision and Pattern Recognition. 1992; vol. 1992: pp. 379–385, Champaign, IL, USA.\n\nOliver NM, Rosario B, Pentland AP: A Bayesian computer vision system for modeling human interactions. IEEE Transactions on Pattern Analysis and Machine Intelligence. 2000; vol. 22: pp. 831–843,\n\nSuk HI, Sin BK, Lee SW: Hand gesture recognition based on dynamic Bayesian network framework. Pattern Recogn. 2000; 43: 3059–3072.\n\nNatarajan P, Nevatia R: View and scale invariant action recognition using multiview shape-flow models. 2008 IEEE Conference on Computer Vision and Pattern Recognition. 2008; pp. 1–8. Anchorage, AK, USA.\n\nNing H, Xu W, Gong Y, Huang T:Latent pose estimator for continuous action recognition. Computer Vision--European Conference on Computer Vision 2008. Marseille, France:Springer;2008; vol. 43. : pp. 419–433.\n\nVail DL, Veloso MM, Lafferty JD: Conditional random fields for activity recognition. Proceedings of the 6th International Joint Conference on Autonomous Agents and Multiagent Systems. 2007; vol. 1: pp. 235.\n\nKiros R, Zhu Y, Salakhutdinov RR, et al.: Skip-thought vectors. Adv. Neural Inf. Proces. Syst. 2015; 1: 3294–3302.\n\nGrushin A, Monner DD, Reggia JA, et al.: Robust human action recognition via long short-term memory. The 2013 International Joint Conference on Neural Networks (IJCNN). 2013; vol. 25: pp. 1–8.\n\nVeeriah V, Zhuang N, Qi GJ: Differential recurrent neural networks for action recognition. 2015 IEEE International Conference on Computer Vision (ICCV). 2015; vol. 4: pp. 4041–4049.\n\nDu Y, Wang W, Wang L: Hierarchical recurrent neural network for skeleton based action recognition. 2015 IEEE Conference on Computer Vision and Pattern Recognition (CVPR). 2015; vol. 23: pp. 1110–1118.\n\nLeung KM: Naive bayesian classifier. Polytechnic University Department of Computer Science/Finance and Risk Engineering;2007; pp. 123–156.\n\nPeterson LE: K-nearest neighbor. Scholarpedia. 2009; 4(2): 1883. Publisher Full Text\n\nSwain PH, Hauska H: The decision tree classifier: Design and potential. IEEE Trans. Geosci. Electron. 1977; 15(3): 142–147. Publisher Full Text\n\nLiaw A, Wiener M: Classification and regression by randomForest. R news. 2002; 2(3): 18–22.\n\nDomínguez-Almendros S, Benítez-Parejo N, Gonzalez-Ramirez AR: Logistic regression models. Allergol. Immunopathol. 2011; 39(5): 295–305. Publisher Full Text\n\nFéraud R, Clérot F: A methodology to explain neural network classification. Neural Netw. 2002; 15(2): 237–246. Publisher Full Text"
}
|
[
{
"id": "212045",
"date": "19 Dec 2023",
"name": "Nurul Amin Choudhury",
"expertise": [
"Reviewer Expertise Human Activity Recognition",
"AI-ML",
"Feature Engineering",
"Domain Adaptation",
"eHealth Applications",
"Neural Networks."
],
"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 uses wearable sensor data to use multiple machines and deep learning models to recognise daily human activities. The overall idea of the paper is satisfactory but needs significant revisions and state-of-the-art benchmark comparisons, methodologies inclusion and rigorous testing. 1. The authors fail to describe the dataset adequately. Stating the source of the dataset is not sufficient. Please study the papers like - N. A. Choudhury and B. Soni, \"An Adaptive Batch Size-Based-CNN-LSTM Framework for Human Activity Recognition in Uncontrolled Environment,\" in IEEE Transactions on Industrial Informatics, vol. 19, no. 10, pp. 10379-10387, Oct. 2023, doi: 10.1109/TII.2022.3229522 and many more for detailed information. 2. The paper starts with recognising human activities using raw sensor data. However, the UCI dataset has extracted features from raw sensor data, how the authors incorporated raw sensor data from the UCI-HAR dataset. 3. The paper needs to be better written in the form of scientific information, grammar and overall representation. Please use a software tool and verify the draft. 4. The literature survey needs to be done appropriately. Include recent and good-quality journals and top-tier conference papers. 5. Data Cleaning or pre-processing needs to be explained more clearly, and a feature fusion pipeline must be used for enhanced activity recognition performance. 6. Both the abstract and conclusion could be better written. Please rewrite it by incorporating the paper's contributions and novelties. 7. The models' explanation needs to be revised in the paper by incorporating and highlighting the hyperparameters. 8. Achieved results are not compared with the benchmark models.\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? 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? No",
"responses": [
{
"c_id": "10927",
"date": "13 Apr 2024",
"name": "Keerthi Varadhi",
"role": "Author Response",
"response": "1. The authors fail to describe the dataset adequately. Stating the source of the dataset is not sufficient. Please study the papers like - N. A. Choudhury and B. Soni, \"An Adaptive Batch Size-Based-CNN-LSTM Framework for Human Activity Recognition in Uncontrolled Environment,\" in IEEE Transactions on Industrial Informatics, vol. 19, no. 10, pp. 10379-10387, Oct. 2023, doi: 10.1109/TII.2022.3229522 and many more for detailed information. Answer: Thank you for the suggestion; we described the dataset in detail in the updated paper. Top of Form 2. The paper starts with recognizing human activities using raw sensor data. However, the UCI dataset has extracted features from raw sensor data, how the authors incorporated raw sensor data from the UCI-HAR dataset. Answer: Thank you for your suggestion. We have provided a detailed description of the dataset in the updated paper. 3. The paper needs to be better written in the form of scientific information, grammar and overall representation. Please use a software tool and verify the draft. Answer: Thank you for your suggestion. We have addressed all grammatical mistakes with the assistance of software tools in the updated paper. 4. The literature survey needs to be done appropriately. Include recent and good-quality journals and top-tier conference papers. Answer: Thank you for your suggestion. We have incorporated additional recent papers from reputable journals such as Springer, Elsevier, and IEEE into the updated literature review. 5. Data Cleaning or pre-processing needs to be explained more clearly, and a feature fusion pipeline must be used for enhanced activity recognition performance. Answer: Thank you for your suggestion. We have provided a detailed explanation of the pre-processing steps and included a paragraph on the fusion pipeline in the updated paper. 6. Both the abstract and conclusion could be better written. Please rewrite it by incorporating the paper's contributions and novelties. Answer: Thank you for your suggestion. We have rewritten the abstract and conclusion, incorporating the contributions into the updated paper. 7. The models' explanation needs to be revised in the paper by incorporating and highlighting the hyperparameters. Answer: Thank you for your suggestion. We have revised the model explanation in the updated paper, emphasizing the inclusion of hyperparameters. 8. Achieved results are not compared with the benchmark models. Answer: Thank you for your suggestion. We have compared the results with benchmark models in the updated paper."
}
]
}
] | 1
|
https://f1000research.com/articles/12-247
|
https://f1000research.com/articles/12-777/v1
|
04 Jul 23
|
{
"type": "Systematic Review",
"title": "Lessons learned during the health crisis caused by COVID-19 in the work of the nursing professional: A systematic review",
"authors": [
"Monica Elisa Meneses-La-Riva",
"Víctor Hugo Fernández-Bedoya",
"Josefina Amanda Suyo-Vega",
"Rosario Violeta Grijalva-Salazar",
"Hitler Giovanni Ocupa-Cabrera",
"Sofía Almendra Alvarado- Suyo",
"Giovanni Di Deus Ocupa-Meneses",
"Hitler Giovanni Ocupa-Cabrera",
"Sofía Almendra Alvarado- Suyo",
"Giovanni Di Deus Ocupa-Meneses"
],
"abstract": "The health crisis caused by COVID-19 impacted the dynamics of the work of health professionals, specifically in nursing professionals who were aware of the essential need for care and a safe environment to reduce in-hospital risks and mortality indicators. The study aimed to analyze the scientific evidence on the lessons learned during the health crisis in the work of the nursing professional, and the analysis of scientific articles published between 2020 and 2023 in the Scopus databases, obtaining a total of 30 articles. The findings show that there is a need to adopt health contingency policies to respond to health crises, as well as to establish and apply coping strategies in health professionals to avoid the impact on their mental health. Additionally, it is important to recognize their role in society. In conclusion, contingency policies and coping strategies must be developed to ensure the safety and well-being of nursing professionals and prevent the impact on their mental health during health crises like the one caused by COVID-19. Furthermore, it is important to recognize and value the fundamental role of nursing professionals in disease prevention and care in society and continue to work on developing policies and support strategies for health professionals to ensure their safety and well-being during health crises.",
"keywords": [
"Lessons learned",
"health crisis",
"COVID-19",
"nursing work",
"nurse"
],
"content": "Introduction\n\nThe coronavirus disease 2019 (COVID-19) pandemic has undoubtedly been one of the most impactful events in recent years. It began in 2019 when the first case was reported in Wuhan, China. Since then, the disease’s evolution has affected millions of people worldwide, increasing morbidity and mortality indicators. Additionally, this pandemic has had a decisive impact on multiple aspects, such as health, economy, and society in general (Suyo-Vega et al., 2022; Fernández-Bedoya et al., 2023; Maldonado-Cueva et al., 2023). Although it has highlighted weaknesses in global preparation and response, it has also emphasized the importance of international cooperation and solidarity to face global challenges (Pratiwi et al., 2022; Qu, 2023). In conclusion, the COVID-19 pandemic has been an unprecedented experience that has left important lessons for the future (Doraiswamy et al., 2021; Romiti and Talerico, 2021; Clarke et al., 2022). While it has been a time of great uncertainty and difficulty, it has also shown the importance of working together as a global community to overcome the challenges we face (WHO, 2020a).\n\nHowever, COVID-19 has had a significant impact on the mental health of nurses worldwide, who have been on the front line of the pandemic response, being at a greater risk of exposure to the virus, and carrying a higher workload burden and emotional stress (WHO, 2020b). Within the nursing community, it was found that 16.8% experienced symptoms of depression, 46.4% reported anxiety, 22.4% reported stress, and 77.6% reported insomnia. These issues were more prevalent among older nurses, those in permanent positions, nurses with extensive experience, and those with comorbidities that put them at risk. Additionally, nurses who had less leisure time and worked longer hours also exhibited higher levels of these symptoms. Burnout was detected in 50.5%, and fear of COVID-19 in 46.9% (Simón et al., 2022). On the other hand, the precariousness of the healthcare system in which healthcare workers operate has led to Mexico being one of the countries with the highest number of deaths among medical and nursing personnel due to COVID-19 globally. These workers have also faced reprisals, arrests, detentions, threats, and dismissals for expressing or making public their demands and the conditions in which they work (Agostoni, 2021). Regarding this matter, the State of the World’s Nursing 2020 report titled “Investing in Education, Jobs, and Leadership” provides an estimation that there are approximately 28 million nursing professionals globally. This figure accounts for over half of the total number of healthcare professionals. It also highlights that there is still a global deficit of 5.9 million nursing professionals, mostly in countries in Africa, Southeast Asia, the Eastern Mediterranean Regions of WHO, as well as in some countries in Latin America (Ribeiro et al., 2020; CEPAL and OPS, 2021).\n\nLikewise, the College of Nurses in Peru, through its website, reported that it has a total of 96,347 registered nurses; as of January 18, 2021, a total of 94 nurses have died, and more than 6,000 have been infected. Negative impacts include “issues related to gender, the risk of violence, the excessive duration of working hours, and unfair treatment of migrant personnel, which affect the nursing profession.” To address the deficiencies in the system, contracts were created to reduce the shortage of professionals. According to data from the General Directorate of Human Resources of the Peruvian Ministerio de Salúd (Ministry of Health, MINSA), these contracts benefited approximately 8,000 nurses, reaching a total of 43,250 professionals in November 2020. However, this incorporation of new professionals into the healthcare system exposed them to precarious employment, essentially without labor rights, and the risk of unemployment as the severity of the epidemic fluctuated (Iturri de la Mata et al., 2020; Ministerio de Salud (MINSA), 2021).\n\nIt is important to note that the mental health of nursing staff not only affects their individual well-being but also has an impact on the quality of care they provide to patients, as fatigue and emotional stress can lead to errors and a decrease in the quality of care (Ferrán and Trigo, 2021; Loyola da Silva et al., 2021; Marques and Saraiva, 2022). In addition, it is essential to pay attention to the mental health of nurses and provide adequate support and resources to cope with the implications of the pandemic, which should include the implementation of psychological support programs and the promotion of self-care and well-being practices (Franco Coffre, 2019; Alam and Parveen, 2021).\n\nIn Ecuador, it was determined that the main signs and symptoms presented by nursing staff are: stress, fear, anxiety, depression, and lack of concentration in performing the tasks required by their work. These were the staff considered to be on the front line of direct care and, during the pandemic, present a medium level of mental health impact (Marques and Saraiva, 2022). It is concluded that nursing staff are not only the most exposed to infection but also the receivers of patients’ pain and suffering and, therefore, from a psychological point of view, they are more vulnerable (Tarqui Mamani and Quintana Atencio, 2019; Morales Ramón et al., 2020; Singh and Subedi, 2020; Quiroz-Figueroa et al., 2022).\n\nThe explored scientific evidence allows us to support nursing faculties worldwide. When preparing for future pandemics, it is crucial to include self-care, evidence-based practices, protocols, and enhanced communication among healthcare professionals in the planning process (Riess et al., 2023). Furthermore, a review study showed that the pandemic impacts nursing work routines, updating measures to prevent occupational infections and pressure injuries from the use of protective equipment, attention to mental health, infection rates among nurses for greater visibility and recognition of the position’s importance in healthcare (Loyola da Silva et al., 2021). The purpose of this systematic review was to analyze the scientific evidence on the impact of the COVID-19 pandemic on the job performance of nursing professionals. The contributions seek to make visible the main strategies, techniques, and procedures carried out by nurses as key players in the management of change in the healthcare field (Nieves et al., 2020), to avoid the repercussions of dealing with a health crisis.\n\n\nMethods\n\nThe study was a systematic, narrative review (Moreno et al., 2018). Scientific evidence was searched for in the Scopus database published in English and Spanish from 2020 to 2023 to fulfill the research objectives. The search was conducted on 1 April, 2023. Search engines were used through synonym equations or alternative terms such as (“Mental health nurses” AND “COVID-19”) and (“Enfermeras de salud mental” AND “COVID-19”).\n\nThe initial search conducted on the Scopus database generated a total of 56 records. Among these, 23 articles were identified but had to be removed due to lack of access from the publisher, resulting in 33 accessible records. After applying filters based on the inclusion and exclusion criteria, a total of 30 eligible records remained. From these, four duplicates were eliminated, leading to a final selection of 30 records. With all the information collected, the following research question was addressed: What is the scientific evidence on lessons learned from the health crisis in the nursing profession? In order to accomplish the objectives, a comprehensive review of the database was conducted. The titles, abstracts, and contents of each document were thoroughly evaluated to categorize the studies. Data were then extracted from the preselected and selected studies, and ultimately, conclusions were presented based on the analysis and interpretation of the data. That said, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) elements of reporting were used, and the flow diagram detailed in Figure 1 was presented.\n\n\nResults\n\nTable 1 shows the findings resulting from the systematization of the identified evidence.\n\n\nDiscussion\n\nThe findings from the review of scientific articles shed light on the impact of COVID-19 on the nursing profession, and were categorized into the following:\n\nThe main problems that arose during the pandemic are related to chaos and confusion due to significant changes in the structure of health care centers and patient care, often exacerbated by hospital management, inadequate ethical redistribution, and resource allocation (Ménard et al., 2022). Additionally, the lack of staffing and material resources (Virani, 2021) in nursing care were situations that led to constraints or feelings of frustration in the face of the health crisis, combined with illness, death, and despair due to high numbers of patients being constantly admitted (Agostoni, 2021), fear (Becerra-Medina et al., 2022), stress (Bartzik et al., 2021; Boned-Galán et al., 2022), anxiety (Savci et al., 2021; Becerra-Medina et al., 2022), depression (Galehdar et al., 2020; Naeim et al., 2020; Esteban et al., 2021; Ali et al., 2023), moral distress (Virani, 2021; Tavakol et al., 2023), an indicator of increased workload (Malinowska-Lipień et al., 2021), quality of life (Boned-Galán et al., 2022), sleep disorder (Boned-Galán et al., 2022; Nishihara et al., 2022) emotional exhaustion (Saravanan et al., 2022; Stefanowicz-Bielska et al., 2022), fatigue (Becerra-Medina et al., 2022; Peng et al., 2022; Stefanowicz-Bielska et al., 2022), psychological well-being disturbance (Nishihara et al., 2022; Ali et al., 2023), mental and physical illness (Stefanowicz-Bielska et al., 2022), increased occupational risks to personal safety (Huff et al., 2023), and negative emotional reactions (Ménard et al., 2022).\n\nThe scientific evidence obtained shows that during the health crisis, nurses working in hospitals were alert and concerned about protecting themselves from the disease to avoid contaminating both their patients and families (Virani, 2021). It should be noted that society recognized the work of nurses on the front line of care, but they were also stigmatized for the high risk of infection or transmission (Singh and Subedi, 2020). However, nurses demonstrated that they can maintain their health despite a pandemic by mobilizing generalized resistance and resilience resources to prioritize the care required by society (Bucher et al., 2021).\n\nProtective factors or buffers to prevent negative effects on the mental health of nurses in the pandemic work environment (Bartzik et al., 2021) included engaging in stress-reducing activities such as exercise, breathing, yoga, relaxation techniques, and engaging in preferred sports. Additionally, teamwork was promoted, along with dialogue, to avoid crises (Esteban et al., 2021); maintaining a positive, hopeful attitude and behavior (Galehdar et al., 2020), promoting humor, happiness, psychological support from experts as a support for help. Nursing professionals presented symptoms of sleep disorders for which they indicated consuming healthy foods, relaxing beverages, listening to soft music, and avoiding terrifying news that affect their well-being (Naeim et al., 2020).\n\nRegarding hospital care management, continuous support from managers was included in the hospital rooms, as well as psychological support, which included implementing personal protection and safety measures (Tang et al., 2022). In everyday practice, the use of specialized materials for each medical intervention was encouraged (Ribeiro et al., 2022). It is important to highlight that working together and in coordination with the health institution was a priority, as an essential safe environment for nurses to offer and manage care in an integral and humane way was required for the new and critical tasks experienced (Thude et al., 2021). Thus, the activities of supervision, anticipation, cooperation of new learning in the nurse’s work constituted a solid structure of resilience-performance network of the team of nurses during the pandemic (Wang et al., 2023).\n\nCare management had to innovate with new nursing practices and improve teamwork and camaraderie. Regarding the balance between work and home, it was a difficult and painful challenge for nurses who had to isolate themselves mostly to avoid any type of contagion; personal disinfection and the use of personal protective equipment caused havoc in skin injuries, urinary infections, and respiratory problems, among others. This experience nursing professionals went through is a positive development in terms of patient improvements, achievements, and positive aspects that create optimism about the future (Ménard et al., 2022). It is important to generate dialogue tables to impart health policies that adjust to society’s needs in the face of health crises. Additionally, health planners and managers must work on the acquisition of facilities and personal protective equipment for patients and nurses as established protocols, to ensure the safety of those being cared for and caregivers (Tavakol et al., 2023).\n\nIt is important to mention that the value of life was a latent priority in healthcare professionals, especially nursing professionals, who stood out for empathy, emotional intelligence (Lin et al., 2022), spiritual intelligence (Aliabadi et al., 2021), psychological resilience to reduce emotional exhaustion (Lin et al., 2022), and self-efficacy in emotional regulation (Wu et al., 2022).\n\nIt is essential that nursing education and curricula include continuous training programs related to crisis management for decision-making (Aliabadi et al., 2021; Bucher et al., 2021), effective training that includes evidence-based practice and clinical skills (Calkins et al., 2023). Psychological interventions are recommended to address the mental health issues still unresolved by nurses and help them overcome the impact of the pandemic (Maideen et al., 2022). Providing suitable working conditions, a safe working environment, continuous training for competency development, recognition for their work, and job satisfaction to prevent the talent drain due to high staff turnover in healthcare institutions (Lin et al., 2022) is also suggested. Improving communication skills, providing individual training to prevent moral distress in nursing personnel, and reinforcing an ethical climate (Tavakol et al., 2023) are further recommended. It is crucial to implement systems that monitor and support the mental health of nurses, as well as encourage them to prioritize self-care methods and practices. These measures are essential in preventing conditions such as anxiety, depression, post-traumatic stress disorder, and other mental health-related issues among nurses. (Calkins et al., 2023) should also be put in place. International institutions, governments, and healthcare organizations should develop strategies to support nurses’ efforts to strengthen their professionalism (Lee et al., 2023). While technology can support nursing care, there are limitations in dealing with the high demand for quality care, satisfaction, and human warmth (Kang et al., 2023).\n\nThe literature identified gaps that still need to be studied, and it is suggested that further research explore themes such as availability of personal protective equipment, training in prevention measures, healthcare provision, emotional support, and recognition, as well as factors that influenced access to these resources, such as geographical location or work conditions. Stigmatization of nurses who worked during the pandemic in different contexts, as well as stereotypes and prejudices about nursing professionals, are also aspects that need to be investigated.\n\nFuture research endeavours should focus on examining the long-term effects of the health crisis on the overall well-being, job satisfaction, and retention of nursing professionals. By delving into these aspects, a more comprehensive understanding of the lasting impact of the crisis on nurses can be obtained. This knowledge can inform strategies and interventions aimed at promoting their well-being, enhancing job satisfaction, and improving retention rates within the nursing workforce.\n\nFurther research could also investigate innovative practices and strategies that emerged during the crisis. This includes exploring the use of technology, telehealth, and remote monitoring, as well as examining the effectiveness of new models of care delivery that were implemented during the pandemic.\n\nFinally, conducting comparative studies across different healthcare systems and countries can provide valuable insights into the variations in responses to the health crisis and identify best practices that can be adopted in different contexts.",
"appendix": "Data availability\n\nZenodo: Data for Lessons learned during the health crisis caused by COVID-19 in the work of the nursing professional: A systematic review, https://doi.org/10.5281/zenodo.8000674 (Meneses-La-Riva et al., 2023a).\n\nZenodo: PRISMA 2020 checklist for “Lessons learned during the health crisis caused by COVID-19 in the work of the nursing professional: A systematic review”, https://doi.org/10.5281/zenodo.8000659 (Meneses-La-Riva et al., 2023b).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAgostoni C: Médicos, enfermeras y pacientes: entre las contradicciones, la incertidumbre y las carencias en tiempo de covid-19 en México. Hist. Cienc. Saude Manguinhos. 2021; 28: 863–867. PubMed Abstract | Publisher Full Text\n\nAlam M, Parveen R: Covid-19 and Tourism. Int. J. Adv. Res. 2021; 9: 788–804. Publisher Full Text\n\nAli EA, Sehlo MG, Hussein RA, et al.: Prevalence and correlates of depressive symptoms among nurses during COVID-19 pandemic. Egypt. J. Neurol. Psychiatry Neurosurg. 2023; 59. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAliabadi PK, Zazoly AZ, Sohrab M, et al.: The role of spiritual intelligence in predicting the empathy levels of nurses with COVID-19 patients. Arch. Psychiatr. Nurs. 2021; 35: 658–663. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBartzik M, Aust F, Peifer C: Negative effects of the COVID-19 pandemic on nurses can be buffered by a sense of humor and appreciation. BMC Nurs. 2021; 20: 212–257. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBecerra-Medina LT, Meneses-La-Riva ME, Ruíz-Ruíz MT, et al.: Mental health impacts of nurses caring for patients with COVID-19 in Peru: Fear of contagion, generalized anxiety, and physical-cognitive fatigue. Front. Psychol. 2022; 13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBoned-Galán Á, López-Ibort N, Gascón-Catalán A: Sleep disturbances in nurse managers during the early and late stages of the COVID-19 pandemic. Front. Psychol. 2022; 13: 1–9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBucher CO, Delmas P, Oulevey Bachmann A, et al.: Stressors, self-reported overall health, potential protective factors and the workplace well-being of nurses during the COVID-19 pandemic in Switzerland: A longitudinal mixed-methods study protocol. BMJ Open. 2021; 11: 1–9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCalkins K, Guttormson J, McAndrew NS, et al.: The Early Impact of COVID-19 on Intensive Care Nurses’ Personal and Professional Well-Being: A Qualitative Study. Intensive Crit. Care Nurs. 2023; 76: 103388. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuff NR, Liu G, Chimowitz H, et al.: COVID-19 related negative emotions and emotional suppression are associated with greater risk perceptions among emergency nurses: A cross-sectional study. Int. J. Nurs. Stud. Adv. 2023; 5: 100111. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIturri de la Mata JA, Gallegos Pacheco RÁ, Brou Gonzáles PS, et al.: Enfermería y Covid-19 en el Perú. Enfrentando hegemonías. Combatiendo una pandemia. Construyendo una profesión.2020.\n\nKang HS, Koh IS, Makimoto K, et al.: Nurses’ perception towards care robots and their work experience with socially assistive technology during COVID-19: A qualitative study. Geriatr. Nurs. (Minneap). 2023; 50: 234–239. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee W, Pyo J, Ock M, et al.: Nurses’ adaptations to changes on a COVID-19 ward in South Korea: A qualitative study. Heliyon. 2023; 9: e13926. 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Lancet. 2023; 401: 820. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQuiroz-Figueroa M, Segovia-Piguabe MS, Salvador-Cortez KR, et al.: Salud mental del personal de enfermería y sus repercusiones en el cuidado del paciente con Covid-19. Rev. Científica Dominio Las Ciencias. 2022; 8: 839–858.\n\nRibeiro DO, Gomes GC, de Oliveira AMN , et al.: Obstetric violence in the perception of multiparous women. Rev. Gauch. Enferm. 2020; 41: e20190419. PubMed Abstract | Publisher Full Text\n\nRibeiro OM, Lopes P, Coimbra VMO, et al.: Impact of COVID-19 on the Environments of Professional Nursing Practice and Nurses’ Job Satisfaction. Int. J. Environ. Res. Public Health. 2022; 19. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRiess D, Mersiovsky A, Gruhn C: Nurse Educators’ Perceptions and Self-efficacy in Response to COVID-19: A Scoping Review. Nurse Educ. 2023; 48: E47–E52. 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}
|
[
{
"id": "225628",
"date": "27 Nov 2023",
"name": "Fatjona Kamberi",
"expertise": [
"Reviewer Expertise Nursing education",
"healthcare",
"mental health",
"public health",
"heath education and promotion",
"cancer screening"
],
"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 valuable systematic article for the nursing profession, including the development and related policies. However, the article has an inconsistency between the introduction part and the objective. The main objective is to review the performance indicators of nursing work during the pandemic, while the introduction is very heterogeneous in this regard, failing to give a clear picture of this problem. In addition, due to this inconsistency, it's very difficult to assess the added value of this review. Also, the geographic area that covers this review is not stated.\nThe method section it is not completely explained. How about the reconciliation of the articles in the Spanish and English language? In the table it was not mentioned which article is in English and which in Spanish. In addition, the research question differ from the main objective. How many researcher were engaged in the search process etc.?\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes",
"responses": []
},
{
"id": "252516",
"date": "21 Mar 2024",
"name": "Lila de Tantillo",
"expertise": [
"Reviewer Expertise Nursing"
],
"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 vitally important topic and I commend the authors for the work they have conducted on this subject. However, in the present form the paper does not appear to be a systematic review, or does not include in the text a description of the methodology to demonstrate that it is a systematic review. Specifically, the subject(s) being examined are far too broad - is this paper looking at mental or physical health consequences of the pandemic on nurse? (or papers that specifically looked at both?) and do not necessarily match the proposed search. Therefore, the intent of the manuscript should be clarified along with a strong explanation of the need for this knowledge (certainly it is implied, but once the focus is made clear then the rationale for the specific focus can be emphasized.) This establishes the setting for the key component needed, providing the key words and detailed procedures used in the paper. (Not examples, but the specific databases and terms.) Ideally all the findings would be reported according to the PRISMA outline, or in a similar method, to the degree possible. For example: What does it mean there were \"search engines\"? Was any database used besides Scopus - none was mentioned, but the PRISMA mentions duplicates removed? And of greatest source of uncertainty was the search of terms \"mental health nurses\" AND \"COVID-19.\" The title of work and introduction focuses on mental and physical health impacts of nurses, not on the role of mental health nurses (does not mention them at all in fact), so the meaning of this was unclear. I would suggest to the authors to revise work to provide information that clarifies and aligns elements of the paper. Perhaps in so doing they may determine this paper more closely resembles the parameters of a narrative review rather than a systematic review. I wish them the very best as they continue with this significant line of inquiry.\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? No\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly",
"responses": []
},
{
"id": "184252",
"date": "16 Sep 2024",
"name": "Donatella Marazziti",
"expertise": [
"Reviewer Expertise Clinical Psychiatry",
"Neurobiology",
"Psychopharmacology",
"Clinical 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 paper is a narrative review highlighting the impact of Covid-19 pandemic on nursing professionals, one of the most hit category of workers. The authors commented on the available literature and stress the fundamental role of nurses during the pandemic and in general during health crises. Therefore, it would be necessary that specific policies in hard times should be directed towards implementing preventing mental health problems and increasing coping strategies and resilience amongst nursing professionals. The paper is timely and well written, with no flaws.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/12-777
|
https://f1000research.com/articles/13-1316/v1
|
04 Nov 24
|
{
"type": "Method Article",
"title": "Ex-vivo models of post-surgical residual disease in human glioblastoma",
"authors": [
"Ola Rominiyi",
"Connor McGarrity-Cottrell",
"Katie N Myers",
"Callum G Jones",
"Kelsey Wosnitzka",
"Sophie T Williams",
"Aurelie Vanderlinden",
"Andra-Gabriela Antohi",
"Natividad Gomez-Roman",
"Anthony J Chalmers",
"Saurabh Sinha",
"David A Jellinek",
"Thomas A Carroll",
"Dennis Wang",
"Andrea Cavalli",
"Veejay Bagga",
"Yahia Al-Tamimi",
"Mark J Dunning",
"Spencer J Collis",
"Connor McGarrity-Cottrell",
"Katie N Myers",
"Callum G Jones",
"Kelsey Wosnitzka",
"Sophie T Williams",
"Aurelie Vanderlinden",
"Andra-Gabriela Antohi",
"Natividad Gomez-Roman",
"Anthony J Chalmers",
"Saurabh Sinha",
"David A Jellinek",
"Thomas A Carroll",
"Dennis Wang",
"Andrea Cavalli",
"Veejay Bagga",
"Yahia Al-Tamimi",
"Mark J Dunning"
],
"abstract": "Background Glioblastoma is a highly infiltrative, currently incurable brain cancer. To date, translation of novel therapies for glioblastoma from the laboratory into clinical trials has relied heavily on in vitro cell culture and murine (subcutaneous and orthotopic) xenograft models using cells derived from the main bulk of patient tumours. However, it is the residual cells left-behind after surgery that are responsible for disease progression and death in the clinic. A lack of substantial improvements in patient survival for decades suggests commonly used murine xenograft models, a key step before clinical trials, do not reflect the biology of residual disease in patients.\n\nMethods To address this, we have developed the ‘Sheffield Protocol’ to generate ex vivo models that reflect both resected, and post-surgical residual disease from the same patient. The protocol leverages parallel derivation of inherently treatment-resistant glioblastoma stem cells (GSCs) from ‘core’ and distant ‘edge’ regions through careful macrodissection of a large en bloc specimen, such as from a partial lobectomy for tumour, followed by tissue dissociation and propagation in serum-free media. Opportunistic en bloc specimen use can liberate the most distant infiltrative cells feasibly accessible from living patients.\n\nResults We provide an example illustrating that resected and residual disease models represent spatially divergent tumour subpopulations harbouring distinct transcriptomic and cancer stem cell marker expression profiles. We also introduce the ‘Sheffield Living Biobank’ of glioma models (SLB) that incorporates over 150 GSC lines from 60+ patients, including 44+ resected and residual models, which are available for academic use via MTA.\n\nConclusions These models provide a novel tool to reduce animal xenograft usage by improving candidate drug triage in early preclinical studies and directly replacing animal studies for some therapies that are post-Phase 1+ clinical trial for other cancers/conditions to, ultimately, deliver more effective treatments for post-surgical residual disease in glioblastoma.",
"keywords": [
"Glioblastoma",
"residual disease",
"patient-derived models",
"3D models",
"replacement."
],
"content": "\n\n\n\nScientific benefits:\n\n\n\n• Unique access to the most brain-invasive GSCs feasible in living patients.\n\n• Patient-matched comparison of biology in GSCs from resected and typically residual regions.\n\n• Avoidance of cell selection based on metabolic features (including 5-ALA metabolism) during derivation.\n\n• Detailed and regularly updated associated clinicopathological data.\n\n• Embeds intra-tumoural heterogeneity assessment early in translational pipelines to ensure only treatments with activity against residual disease are progressed.\n\n3Rs benefits:\n\n\n\n• Reduce use of animal-based preclinical models through improved drug candidate triage.\n\n• Replace use of animal-based preclinical models to fast-track candidate therapies within drug repurposing strategies (from both other cancers and other conditions).\n\n• More rapid end assay data generation compared to animal studies.\n\nPractical benefits:\n\n\n\n• Compatible with commonly used laboratory assays.\n\n• Robust 3D clonogenic survival assays.\n\n• Over 44 resected and residual GSC models available for academic use via MTA for groups wishing to replace/reduce PDX model usage.\n\nCurrent applications:\n\n\n\n• Focused functional and omic profiling of the differences between GSCs from tumour core and distant invasive edge regions.\n\n• Evaluation of spatially-mediated differences in therapeutic response.\n\n• Preclinical assessment of therapeutic efficacy in normally ‘left-behind’ disease.\n\nPotential applications:\n\n\n\n• Integration into high-throughput drug screening strategies to prioritise candidate therapies for ‘left-behind’ disease.\n\n• Future academic-industry MTAs to support residual disease informed drug development and evaluation.\n\n\nIntroduction\n\nGlioblastoma is a devastating incurable brain cancer that contributes to around 190,000 brain tumour related deaths/year globally.1,2 Typically, surgery is performed to remove as much of the tumour as safely possible. However, the highly infiltrative nature of glioblastoma underlies a lack of distinct tumour-brain interface intraoperatively and ensures residual disease at a macroscopic or microscopic level is inevitable.3 Subsequently, patients are treated with radiotherapy, temozolomide chemotherapy and increasingly tumour treating fields (TTFields).4 Unfortunately, despite current multi-modal therapy, disease progression occurs within 6-7 months on average and less than 10% of patients survive more than 5 years.5,6\n\nThe failure of preclinical research over the last decade to portend truly substantial improvements in patient survival for glioblastoma, a recognised cancer of unmet need,7 implies that commonly used preclinical models do not fully reflect the complexities of tumour cell biology and therapeutic resistance. Therefore, efforts to increase the clinical and surgical relevance of early preclinical research models may not only enhance our understanding of difficult to treat cancers, but also improve the predictive value of preclinical studies to delineate therapeutic strategies which might confer meaningful benefit for patients.8 In the context of glioblastoma, inherently treatment resistant glioma stem cell (GSC) subpopulations have been identified to exhibit heightened DNA damage response (DDR) activity following current chemoradiotherapy9–11 and contribute to tumour repopulation and disease progression.9,10,12,13 Furthermore, beyond clear patient-to-patient variation,14–16 extensive spatial heterogeneity within each individual tumour contributes to the therapeutic recalcitrance of glioblastoma.17–19 However, both in vitro and in vivo research models used in the laboratory normally do not represent the spatial complexity of human glioblastoma observed in patients.\n\nRodent (particularly mouse) orthotopic patient-derived xenograft (PDX) models are commonly used in glioblastoma research20 and are often viewed as a gold-standard model to investigate candidate therapies prior to clinical trials.21,22 Based on our recent analysis of studies using murine PDX models as patient-specific avatars to evaluate treatment response, in conjunction with data obtained from the GlobalData database detailing current therapeutic development for glioblastoma, we estimate over 20,000 mice were used globally in the setting of patient-specific treatment response prediction over the last 5 years.23 More generally, over 630 research articles published in 2023 mention the use of a glioblastoma animal model (PubMed). Reviewing of a sample of these studies, we find approximately 120 animals are used on average per study. This extrapolates to a conservative estimate of over 75,600 animals per year being used in glioblastoma research globally.\n\nStandard practice in orthotopic PDX models includes the placement of tumor cells into the brain parenchyma of immunodeficient mice or rats, typically leading to observable disease progression and ultimately necessitating animal culling. Numerous advantages are provided by these models including, to some degree, recapitulation of the blood-brain barrier, generation of therapeutic response data, and some information around treatment tolerability. However, despite broad use by the research community, these models are inherently flawed. Orthotopic and subcutaneous tumor implantation in PDX models of glioblastoma, when viewed through the lens of the 3Rs, present ethical challenges due to the harsh procedures involved. To evaluate therapeutic efficacy, tumor growth is often permitted to progress to a specified volume before commencing treatment, with many animals still undergoing symptomatic disease progression and ultimately requiring euthanasia. This approach classifies the studies as 'severe,' reflecting the unavoidable distress, discomfort, and non-survival of the rodent subjects. The time it can take to generate meaningful data using PDX models also represents a further disadvantage. The duration between patient tumour resection to generation of in vivo therapeutic response data using PDX models can take well over a year, as time is required to: passage and expand tumour cells either in vitro or in vivo (rodent-to-rodent) to provide a cohort large enough to evaluate one of multiple treatment strategies/conditions, and, reach a predetermined tumour size/volume before starting treatment. Even where a pre-existing cell line is implanted orthotopically, many months can be required for tumours to grow to an acceptable size prior to treatment. Consequently, we believe the development and implementation of ex vivo cell culture models of residual disease that are more representative of the disease left behind after surgery in patients has the potential for broad impact and defined scientific advantages over animal models (discussed below). These models therefore have the potential to reduce animal usage and replace animal studies in a number of contexts whilst mitigating against some of these flaws.\n\nFrom a scientific perspective, orthotopic PDX models of glioblastoma do not accurately reflect the molecular profile and full spectrum of heterogeneity in patients for numerous reasons. For example, animal-specific evolution of glioblastoma cells following implantation has been reported.24 Furthermore, orthotopic rodent xenografts generated through implantation of either established or more recently patient-derived cell lines often form tumours with negligible-to-limited brain invasion - unlike the highly brain invasive tumours observed in patients.25 To some degree, this may reflect spatial sampling bias since the overwhelming majority of research tissue used to generate these implanted glioblastoma cells will be liberated from the typically resected tumour bulk, rather than more distant, brain invasive disease that is more likely to be left behind after surgery.8\n\nMoreover, due to the technical challenges and infrequency of surgical resection in rodent models, these xenograft systems often fail to replicate the full spectrum of multi-modal therapies routinely administered to glioblastoma patients. As a result, it remains uncertain whether the observed survival benefits in most orthotopic PDX models represent treatment effects on the resectable tumour core, or if they extend to the infiltrative tumour margins that drive disease recurrence in patients. This is clinically relevant, as in patients receiving standard-of-care treatment, only the infiltrative residual cells left behind after surgery are responsible for disease progression and death. In many contexts, such as attempts to apply therapies used for other cancers to glioblastoma or repurposing drugs used to treat other medical conditions, an in vitro alternative with the capability to directly assess treatment response in residual cell populations could provide a more meaningful and clinically-relevant replacement for current animal studies. In the assessment of newly developed therapeutics, in vitro assessment of drug response in residual disease cell populations could help triage candidate drugs – ensuring only those with activity against residual disease progress to in vivo studies to minimise animal usage.\n\nThe translation of innovative glioblastoma therapies from bench to bedside has largely hinged on the use of cells obtained either recently (e.g., primary and ex vivo cultures) or long-established (e.g., immortalized cell lines), all originating from the main bulk of patient tumours that is typically resected during surgery. In light of the limited survival improvements in glioblastoma compared to other cancers, the traditional framework—relying on 2D in vitro studies and subsequent xenograft models with resected cells—has proven inadequate in predicting the response of the brain invasive glioblastoma cells that remain after surgical intervention in the clinic. The expanding arsenal of targeted therapies underscores the necessity for models that more faithfully represent the biology and therapeutic response of post-surgical residual glioblastoma early in the translational research process8 to accelerate the application of next generation therapeutic strategies and combinations to future patients diagnosed with glioblastoma. To address this unmet need, we have developed robust, adaptable ex vivo models of post-surgical residual glioblastoma from human tissue which can be readily used within 2-dimensional and 3-dimensional culture conditions, including within a customised scaffold-based architecture.26,27 These models aim to enrich surgically-relevant investigation of the complex biology of glioblastoma within early preclinical studies, with the potential to replace animal studies in some of these contexts.\n\nSurgical resection, when guided by the anatomical specifics of a case, may occasionally result in the extraction of a large en bloc specimen (such as a partial lobectomy), incorporating areas of infiltrated brain that would typically evade resection. We believe that this tissue provides a crucial resource in modelling and understanding residual disease in glioblastoma. Our ex vivo resected and residual models are based on the generation of parallel, patient-derived GSC lines from the tumour core and adjacent infiltrated brain of suitable specimens. Here, we outline the protocol used to successfully derive parallel, spatially-distinct resected and residual glioblastoma models that can be maintained as either bulk (differentiated) or GSC cultures for a wide range of preclinical research applications to study the unique features of post-surgical residual disease. Crucially, these models may provide a biologically relevant and cost-effective alternative to the use of animals in some preclinical research. For example, they provide a particularly compelling replacement for murine models to assess therapeutic response for treatments which have already progressed beyond phase 1 clinical trials for other types of cancer and/or repurposed medications. Therefore a conservative target of 10% uptake of our ex vivo residual models within glioblastoma research community internationally, with a focus on these settings, could replace the use of over 7,000-8,000 animals per year (based on usage leading to PubMed indexed publications, estimated above), whilst accelerating the translation of comprehensive novel therapeutic strategies into the increasingly adaptive outlook of later stage glioblastoma clinical trials, e.g. The Tessa-Jowell BRAIN-MATRIX trial, 5G and GBM AGILE.1,28\n\n\nMethods\n\nThe procurement of en bloc specimens suitable for resected and residual model generation requires appropriate institutional research ethics. At our institution, all clinical information and specimen acquisition was performed in within the scope of the approved IRB ethics protocol 11-YH-0319 (STH15598) - Yorkshire & The Humber - Leeds East Research Ethics Committee (approved 03/11/2011, substantial amendment approved 01/06/2016) and in adherence to the Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/). Close collaboration across academic and clinical boundaries with input from the neuro-oncology multi-disciplinary team (MDT) is essential. In our experience, the availability of clinical-academic surgeons with experience of navigating both environments has been incredibly useful. However, in the absence of this, ensuring some members of the research team have appropriate approvals to access both the laboratory and neurosurgical operating theatre is vital to visually confirm the correct orientation of specimens is maintained during the transfer process from the clinic to the laboratory. Additionally, clear and regular communication with the theatre team including the theatre team leader, scrub nurses, operating department practitioners, anaesthetists and surgeons is key to maximising successful procurement of these relatively rare samples.\n\n1. Case selection\n\n1.1. ln collaboration with an appropriately qualified neurosurgeon, identify suitable patients based on the inclusion and exclusion criteria detailed in Table 1. Typically, potential candidates are those scheduled for surgical resection of a large suspected high-grade glioma situated anteriorly within the frontal or temporal lobe with a planned resective strategy that is likely to produce an en bloc specimen, usually as a partial lobectomy (see Figure 1A). Importantly, sample acquisition is opportunistic with availability dictated by the tumour characteristics and operating neurosurgeon(s); the research team must never attempt to influence the resective strategy planned by the clinical team.\n\nNOTE: We find weekly clinician/academic-clinician review of cases referred into the neuro-oncology MDT (tumour board meeting) and scans of scheduled neuro-oncology cases invaluable to identify cases as early as possible and provide sufficient time to obtain patient consent.\n\n1.2. Confirm lead/operating neurosurgeon responsible for the patient’s care is supportive of a suitable patient being approached for consent.\n\n1.3. Obtain patient consent as per agreed institutional protocol.\n\n2. Macrodissection\n\nNOTE: Prior to the expected time of specimen retrieval, in the laboratory, disinfect and prepare a class II biological safety cabinet ensuring the availability of the required reagents, plasticware and equipment listed in Tables 2-4 and start warming the following solutions to 37°C: PBS, Accutase, complete GSC media (see Table 5).\n\n2.1. Ensure that a member of the research team is present in theatre as the tumour is being resected.\n\n2.2. Confirm freshly resected en bloc surgical specimen is suitable for parallel resected and residual model derivation in close collaboration with the neurosurgical and/or histopathology team (based on institutional set-up/approvals) – ensuring the specimen contains clear macroscopic evidence of tumour and adjacent tissue with cerebral cortex visible.\n\n2.3. Neurosurgeon (or histopathologist based on institutional processes) divides en bloc specimen along its axis to yield a specimen for clinical histopathology and a separate specimen for research both containing tumour core and adjacent brain tissue.\n\n2.4. A member of the research team immediately transports the pseudonymised research specimen to the laboratory in a clear specimen container within clear specimen bags, whilst maintaining orientation of the sample.\n\nTip: Although we typically find use of transport media/solution unnecessary as our neurosurgical theatres and research laboratory are in close proximity, if desired, research specimens can be transported in sterile normal saline or advanced DMEM/F12 media at room temperature.\n\nNOTE: At our institution, research samples are pseudonymised by assigning a sample specific ‘STH code’ based on date of retrieval and operating list order whilst ensuring no clinical identifiers are present before transport to the research laboratory. A clinical-academic member of the team (OR) maintains the de-pseudonymisation key linking STH code to patient as an encrypted file within the Sheffield Teaching Hospitals IT infrastructure.\n\n2.5. In the laboratory within a biological safety cabinet, transfer sample from the transport container to a 10 cm round tissue culture dish then gently rinse research specimen with PBS and aspirate off – repeat until clear.\n\n2.6. Visually inspect the specimen to ensure tumour core (typically darker with evidence of necrosis) and adjacent infiltrated brain – ‘edge’ region (typically region most distant from tumour core with visible cortex, identified by sulcal/gyral patterning and/or visible grey-white differentiation) are present (see Figure 1B).\n\n2.7. Using a scalpel, divide an approximately 5 mm × 5 mm sample from the ‘innermost’ region to represent the tumour core. Using a separate scalpel, divide a further 5 mm × 5 mm sample from the ‘outermost’ region to represent the infiltrative edge of the tumour. These samples represent resected (core) and typically residual (infiltrative edge) disease. Further 5 mm × 5 mm samples can then be dissected from the intervening regions using a further fresh scalpel to provide intermediate samples (Figure 1B). Separate each sample into an individually labelled culture dish.\n\nTip: We often take additional samples from both ‘core’ and ‘edge’ regions of an en bloc specimen to reflect spatial heterogeneity within each of these regions. We typically number samples (e.g. Core 1, Core 2, Edge 1, Edge 2) and find it helpful to take photographs demonstrating the macroscopic features of each sample prior to GSC derivation. Occasionally, we also take samples from tissue in the intervening region between ‘core’ and ‘edge’ extremities to generate ‘intermediate’ region GSCs.\n\n3. Parallel derivation\n\nDay 0\n\n3.1. Using sharp dissection with a separate scalpel blade (those reserved above) for each sample, mechanically dissect the core, intermediate and edge samples aiming to produce fine pieces ≤1mm3 (see Figure 1C).\n\nNOTE: We find cutting in one orientation using fast, repetitive up-down ‘chopping’ motion of the scalpel, then rotating the plate 90° and cutting again, then rotating a further 45° and cutting again provides fine, evenly divided pieces.\n\n3.2. Add 5 ml of Accutase™ to each sample and pipette up and down using a separate glass or plastic Pasteur pipette for each sample to loosen large cell clumps, then incubate in a humidified cell culture incubator at 37°C, 5% CO2 and 21% O2 for 30 mins.\n\n3.3. Examine each suspension under a microscope then pipette up and down again using a separate glass or plastic Pasteur pipette for each sample and return to the incubator for a further 15-30 mins.\n\n3.4. Repeat step 3.3 until the tissue within each sample is predominantly dissociated and single cells are visible using a light microscope.\n\nTip: We generally find an overall incubation time of 45-90mins at 37°C provides optimal enzymatic dissociation, with exact timing influenced by a number of factors including: the size of each tumour sample; extent and homogeneity of preceding mechanical dissociation, and tumour consistency. Avoid excessive enzymatic dissociation as this can reduce cell viability leading to failure of the culture. We typically progress to step 3.5 as soon as roughly 50% or more of cells are visualised as single cells.\n\n3.5. Using a fresh, sterile 10 ml serological pipette for each sample, transfer the cell-Accutase™ suspensions from the 10 cm dishes to labelled 50 ml Falcon tubes.\n\n3.6. Add 5ml complete GSC media to each 10 cm dish, swirl to collect cells, then transfer this to the corresponding labelled 50 ml Falcon tube using a fresh serological pipette for each sample.\n\n3.7. Filter each suspension through a 100 μm cell strainer rested on top of a second labelled 50 ml Falcon tube.\n\n3.8. Centrifuge each cell suspension (core-filtered, intermediate-filtered, edge-filtered) at 1000 rpm (180 rcf) for 5 mins.\n\n3.9. Very gently aspirate the supernatant whilst tilting each Falcon tube 45° then resuspend the cells in complete GSC media by gentle pipetting up and down 3-4 times using a serological pipette.\n\n3.10. Transfer each cell suspension to a labelled T25 flask using a serological pipette and incubate upright in a humidified cell culture incubator at 37°C, 5% CO2 and 21% O2 for 37°C overnight.\n\nDay 1\n\n3.11. Warm complete media (3 ml per sample plus an additional 3-5 ml excess) in a water bath at 37°C then clean the container/bottle/falcon tube well with 70% IMS prior to use.\n\n3.12. Transfer each GSC suspension (core, intermediate, edge) from old T25 flask to individual, labelled Matrigel™-coated T25 flasks using fresh serological pipettes for each flask and add a further 3ml of fresh complete GSC media.\n\n3.13. Incubate with flasks lying on Matrigel™-coated side in a humidified cell culture incubator at 37°C, 5% CO2 and 21% O2 overnight to begin adherent monolayer formation.\n\nDay 2\n\n3.14. Warm complete media (5-7 ml per sample plus an additional 3-5ml excess) and PBS (5ml per sample plus excess) in a water bath at 37°C then clean the containers/bottles/falcon tubes well with 70% IMS prior to use.\n\n3.15. Gently aspirate media off cells which will now be relatively adherent to the Matrigel™-coated flask using a serological pipette. Rinse very gently once with warmed PBS then aspirate off. Gently add 5-7 ml of fresh, complete GSC media then continue to incubate cells at 37°C, 5% CO2 and 21% O2.\n\nTip: We use appearances of the adherent cells under light microscopy prior to media exchange to guide the volume of media used. For example, using 5 ml complete media if very few adherent cells are observed (e.g. less than 10% flask surface area coverage/confluency) or 7 ml where adherent cells are more readily observed (e.g. greater than 40% flask surface area coverage/confluency)\n\n4. Propagation\n\n4.1. Maintain GSCs as an adherent monolayer (Figure 1D) in Matrigel™-coated flasks (initially in T25 flasks) by replacing complete GSC media 3x per week.\n\n4.2. Once cells are 80-90% confluent, transfer cells from each T25 to a Matrigel™-coated T75 flask. This is performed by gently aspirating off old media using a serological pipette, rinsing very gently once with 5 ml warmed PBS which is aspirated off then adding 0.5 ml Accutase™ and incubating cells in a humidified cell culture incubator at 37°C, 5% CO2 and 21% O2 for 2-3 minutes to detach cells from the Matrigel™ coating. After this, 4.5ml of fresh, warmed complete GSC media is added to the T25 flask and the cell suspension is mixed by gently up-down pipetting 3-4 times using a serological pipette before transferring to a new T75 Matrigel™-coated flask. A further 5ml of warmed complete GSC media is added to the T75 flask before further gentle mixing of the cell suspension as above (3-4 times) and then incubation with flasks lying on the Matrigel™-coated side in a humidified cell culture incubator at 37°C, 5% CO2 and 21% O2.\n\n4.3. Continue to expand GSCs by continued culture with regular media changes (3x per week) and splitting once cells are 70-80% confluent. Cryopreserve multiple vials of GSCs at the earliest available opportunity.\n\nTip: We advocate using patient-derived GSCs within experiments at the earliest passage possible – ideally within 10 passages, but typically less than 20. Nevertheless, we have been able to successfully propagate resected and residual GSCs for over 50 passages, demonstrating the feasibility of long term culture with this protocol, if required. At ultra-early passage (P1-3) we typically split heavy (i.e. 1:2-1:3) to reduce the risk of culture failure. After this stage splitting 1:4-1:10 is usually most appropriate.\n\n4.4. Resected and residual model GSCs can also be cultured in the absence of Matrigel™ (or other adherent substrate) to form neurospheres or larger tumouroid cultures (see Figure 1D right – upper and lower panels).\n\n4.5. To generate differentiated ‘bulk’ tumour cultures, during cell splitting a population of resected and/or residual model GSCs can be transferred to Matrigel™-coated flasks containing serum containing ‘bulk media’ (see Table 3). Performing experiments using both non-GSC enriched ‘bulk’ cultures and GSC cultures in parallel can be useful to establish differences in the biology and therapeutic resistance between these subpopulations.26,29,30\n\nTip: We propagate resected and residual model primary cells in bulk media for at least 5 passages before use in experiments as differentiated bulk cells. It is important when comparing resected and residual model GSCs to bulk cultures – to ensure these have been cultured in parallel and used in experiments at equivalent/near equivalent passage numbers. Additionally, we regularly use flow cytometry, immunoblotting and/or RT-qPCR to confirm reduced stem cell marker expression in differentiated bulk cells (see below).\n\n\n\n• All patients must receive all the usual clinical care.\n\n• Consideration to attempt model derivation should not influence surgical strategy employed by the operating team.\n\n• Valid institutional research ethics approval must be in place.\n\n\n\n• Diagnosis of suspected high-grade glioma based on radiological appearances and/or neuro-oncology MDT consensus.\n\n• Ability to collect the specimen and associated clinical information within agreed timescales.\n\n• Provision of informed consent.\n\n• Brain tumour size greater than 18 mm (across its longest axis) on pre-operative CT/MRI head.\n\n• Tumour situated anteriorly within the frontal or temporal lobes and/or operating neurosurgeon indicates partial lobectomy likely to be required.\n\n\n\n• Patients under 18 years of age.\n\n• Patients undergoing biopsy only.\n\n• Presence of any CAT 3 disease, either currently or no negative result since last screening.\n\n• Patients positive for Covid-19.\n\nA. Selection of patients undergoing partial lobectomy for glioblastoma – schematic representation of unsuitable and suitable planned resections (left) and suitable pre- and post-operative MRI (T1-weighted) following intravenous contrast (right). Regions within the tumour core (for resected model) and adjacent brain tissue affected by the infiltrative edge (for residual model) highlighted in inset. B. En-bloc specimen following hemi-section in theatre for clinical pathology and research (left) before microdissection of the research specimen. Whilst maintaining orientation – the research specimen is subdivided as illustrated (right) to represent core, infiltrative edge, and intermediate (inter.) components for parallel GSC line derivation. C. Parallel derivation of patient-derived GSCs from core and edge of the en-bloc specimen – representative images. D. Representative brightfield light microscopy images (20x magnification) of Sheffield ex vivo resected and residual models. OX-5 and OX-2 core (left column) and edge (middle column) GSCs cultured as monolayers on Matrigel™-coated plasticware are demonstrated (scale bars = 500 μm). Right column (upper) – representative image of OX-5 edge GSCs cultured in non-adherent conditions as 3-dimensional neurospheres (scale bar = 250 μm), and; right column (lower) – representative photograph in non-adherent conditions (T25 flask) as larger 3-dimensional tumoroids following culture for 2 weeks. Scale bars = 200 μm.\n\nOnce successfully propagated, resected and residual cultures can be used within the range of common cell and molecular biology techniques to help better understand the biology of typically residual disease cells relative to those cells normally resected in a patient specific manner. Below, as a proof of concept, we apply common techniques to OX-5 core (resected) and edge (residual) cells – which is one of the first resected and residual models generated in our laboratory.\n\nRT-qPCR was used to confirm whether OX-5 core and edge GSCs demonstrated elevated expression of key glioma stem cell markers relative to their bulk counterparts, and to explore any potential differences between the resected (core) and residual (edge) GSCs. OX-5 GSCs were seeded at a density of 25×105 cells per well into MatrigelTM-coated 6-well plates and incubated at 37°C in 5% CO2 for 48 hours in complete stem media without any treatments. RNA was extracted from primary cells using the Qiagen RNeasy Mini Kit according to the manufacturers protocol. Briefly, media was removed from cultured cells and cells were washed twice with ice cold PBS. PBS was aspirated and 350 μl RLT buffer was added to each well. Cells were dislodged using a cell scraper and transferred to labelled QIAshredder columns before being centrifuged at 8000r.c.f for minutes (4°C). Purple columns were discarded and 350 μl of 70% ethanol was added to the supernatant, which was then transferred to an Rneasy Minispin column and centrifuged for 15 seconds. Flow through was discarded and 700 μl of RW1 buffer was added to each column, which were then centrifuged for a further 15 seconds. This process was repeated twice with 500 μl of RPE buffer, with centrifugation steps of 15 seconds and then 2 minutes. Flow through was discarded at each step, then an additional centrifugation step for 1 minute was used to remove any excess ethanol. Following this, 50 μl Rnase free water per sample was added and these were centrifuged for 1 minute to elute the RNA. Total RNA levels in each sample were quantified using the NanoDrop ND 1000 Spectrophotometer (NanoDrop technologies); this quantifies absorbance a wavelength of 260 nm to establish the concentration of RNA in each sample, and the ratio of sample absorbance at 260/280 was used to confirm purity (absence of contaminants such as protein or phenol, which absorb strongly at/near 280 nm) with ratios ~2.0 deemed to represent ‘pure’ RNA.31 After RNA quantification, samples were stored at -80°C prior to use.\n\nRNA samples were reverse transcribed using the High-Capacity RNA-to-DNA™ Kit (Applied Biosystems™) before the cDNA samples generated were used in triplicate reactions for each probe on a 384-well PCR plate (ThermoFisher Scientific). Each reaction consisted of: 2 μl cDNA, 5 μl TaqMan™ Universal PCR Mastermix (ThermoFisher Scientific), 2.5 μl ddH2O and 0.5 μl of probe (CD133 [probe assay ID: Hs01009259_m1], nestin [Hs04187831_g1], SOX2 [Hs01053049_s1], with GAPDH [Hs02758991_g1] used as a control ‘housekeeping’ gene; ThermoFisher Scientific). The plate was sealed using optical adhesive film (MicroAmp™, ThermoFisher Scientific) and loaded onto a 7900HT Fast Real-Time PCR System (ThermoFisher Scientific) to perform real-time quantitative PCR. The system was set to report 18S FAM with repeats of 40 cycles. Double delta Ct (2-ΔΔCt) analysis was used to determine relative gene expression using an average Ct value from the triplicate runs. At least 3 independent biological repeats of each experiment were performed using early passage (< P10) patient-derived cells of consecutive or near consecutive passage.\n\nImmunoblotting was used to characterise any potential differences in the protein expression of key glioma stem cell markers between core (resected) and edge (residual) OX-5 GSCs. GSCs were seeded at a density of 25×105 cells per well into MatrigelTM-coated 6-well plates and incubated at 37°C in 5% CO2 for 48 hours in complete stem media without any treatments before media removal. Cell monolayers were washed twice in ice-cold (4°C) PBS then stored at -80°C. The plates were then thawed on ice before the addition of 100μl/well of lysis buffer (20 mM Tris-HCl pH 7.5, 150 mM NaCl, 1% Triton X-100, 1 mM DTT and 1 mM EDTA supplemented with 50 U/μl benzonase (Novagen), protease and phosphatase inhibitors (Sigma)). Cells were harvested using a cell scraper and transferred to labelled eppendorfs on ice. Each sample was then vortexed for 5 seconds before incubation on ice for 15 minutes. The cells were then vortexed again for 5 seconds before an additional 15-minute incubation on ice and one final vortex. Cleared lysates were produced by centrifugation of the resulting samples at 15,000 rcf for 15 min at 4°C. Gel electrophoresis was performed using the NuPAGE system (Invitrogen).\n\nLysate (with LDS NuPAGE Sample Buffer, Invitrogen) volumes were calculated to provide 50 μg of protein loaded to each lane on the gels. SeeBluePlus2 Prestained Standard (Invitrogen) was loaded using 10μl alongside the protein samples as a molecular weight reference. Any empty wells were loaded with 5μl of 4x NuPAGE LDS Loading Buffer. The samples were electrophoresed at 140-150V for 90-120 minutes in an Xcell SureLock™ Electrophoresis Mini-Cell or Invitrogen Mini Gel Tank using 1x NuPAGE MOPS buffer (Invitrogen). Subsequently, protein within the gels was transferred to nitrocellulose membranes at 100V for 120 minutes in Mini PROTEAN Tetra Cells (BioRad) using 1x NuPAGE transfer buffer (Invitrogen).\n\nNitrocellulose membranes were then probed for the proteins of interest. All incubation steps took place on a rocking platform (approximately 30 rpm). Briefly, nitrocellulose membranes were blocked for 30 minutes at room temperature in 5% milk (Marvel, Tesco) dissolved in PBS-T. Meanwhile, primary antibodies were diluted to the appropriate concentrations (see below) in PBS containing 5% milk and 0.1% Tween-20 (Sigma). Membranes were then divided, based on the expected location of proteins of interest, then incubated with primary antibodies (CD133 1:1000 [Abcam ab216323 rabbit monoclonal, RRID:AB_2847920]; SOX2 1:500 [Santa Cruz sc-365823 mouse monoclonal, RRID:AB_10842165]; nestin 1:1000 [Abcam ab6142 mouse monoclonal, RRID:AB_305313]; β-tubulin 1:2000 [Abcam ab7792 mouse monoclonal, RRID:AB_306081]) overnight at 4°C on a rocking platform (at approximately 30 rpm) in the cold room. The next day, membranes were washed 3 times (10 minutes each + intervening washes) in PBS-T, before incubation with appropriate secondary antibodies conjugated to horseradish peroxidase (HRP) at a concentration of 1:1000 (polyclonal goat anti-mouse IgG, HRP-linked [Dako P0447, RRID:AB_2617137]; polyclonal swine anti-rabbit IgG, HRP-linked [Dako P0399, RRID:AB_2617141]). Membranes were washed a further 3 times (10 minutes each + intervening washes) in PBS-T, then visualised using Pierce ECL western blotting substrate (ThermoFisher Scientific). In dark conditions, membranes were exposed to medical x-ray film (Fuji Medical Super RX, Fujifilm), then films were developed using a film processor (Mibolta SRX101A, Konica). Film images were then scanned to produce digital images using a scanner (Expression 1680 Pro, Epson).\n\nImmunofluorescence was used to further visualise the relative protein expression of two key glioma stem cell markers (CD133 and nestin) within core (resected) and edge (residual) OX-5 GSCs. GSCs were seeded at a density of 5×105 cells per well in complete stem media onto MatrigelTM-coated coverslips inside a 24-well tissue culture plate. Cells were then incubated at 37°C in 5% CO2 and 21% O2 for 48 hours before all media was aspirated and 2 washes were performed with ice cold (4°C) PBS. The cells were then fixed using ice cold 4% PFA for 10 minutes followed by two washes with ice cold PBS. Cells were then permeabilised using 0.5% Triton X-100 (250 μl in 50 ml) and 3% BSA extraction buffer for 5 minutes at room temperature succeeded by 3 further washes with PBS. Primary antibodies were made up the required concentration in PBS with 3% BSA then 200μl of the required cancer stem cell marker antibodies (CD133 1:250 [Abcam ab216323 rabbit monoclonal, RRID:AB_2847920]; nestin 1:250 [Abcam ab6142 mouse monoclonal, RRID:AB_305313]) were added to each well and then plates were incubated overnight at 4°C in the refrigerator. The following morning the primary antibody was aspirated off before 3 additional gentle washes with PBS, then 200 μl per well of secondary antibody (Alexa Fluor® 594 Goat Anti-Mouse 1:1000 [Life Technologies A11005, RRID:AB_141372] and Alexa Fluor® 488 Goat Anti-Rabbit 1:1000 [Life Technologies A11034, RRID:AB_2576217]) diluted to the desired concentration in PBS with 3% BSA was added before wrapping all plates in foil and incubation at room temperature for 1 hour on a rocking platform (approximately 30 rpm). Following this incubation, the secondary antibody was aspirated off before 3 final washes (5 minutes each) in PBS (the second wash containing DAPI 1:1000) in dark conditions to prevent photo bleaching. Following the final wash, the cover slips were then mounted onto labelled microscope slides using Shandon Immu-Mount (Thermo Scientific). The slides were then stored in the dark to dry overnight.\n\nMicroscopy was performed on a Nikon Eclipse T200 inverted microscope and all images were taken using the Hamamatsu Orca ER camera and 200W mercury-xenon arc lamp at a total magnification of 600x (10x eyepiece, 60x objective). Images were captured using the Nikon NIS-Elements software package with image settings (including contrast, gain, offset) kept constant between experimental conditions. An excellent open access alterative to this software package would be ImageJ/Fiji. All images were converted to TIFF file formats and uploaded to the Collis laboratory Google Drive. Representative images are displayed.\n\nFlow cytometry was used to quantitatively establish any potential difference in protein expression of the key glioma stem cell marker CD133 between core (resected) and edge (residual) OX-5 GSCs. GSCs were seeded at a density of 25×105 cells per well into MatrigelTM-coated 6-well plates and incubated at 37°C in 5% CO2 for 24 hours in complete stem media without any treatments. Media was aspirated off and cells were washed twice in PBS before 500 μl/well of Accutase™ was added. Both media and PBS washes were retained. Following detachment, cells were collected in 500 μl/well of PBS which was added to the media and PBS washes in 15 ml Falcon tubes labelled for each GSC line (OX-5 core and OX-5 edge). These were then centrifuged at 1,200 rpm (260 rcf) for 3 minutes. The supernatant was discarded, leaving a cell pellet to which 1ml of ice cold 70% ethanol was slowly added (whilst gently mixing on vortex for 5 seconds) to aid the fixation of cells in single cell suspension. Cells were left to fix overnight before excess ethanol was spun off and cells washed in PBS twice – centrifuging at 1,200 rpm (260 rcf) for 3 minutes and carefully discarding the supernatant at each stage. Subsequently cells were stained with Pre-conjugated mouse monoclonal [W6B3C1] antibody to CD133 (APC) for Flow Cytometry (CD133 1:10 [10 ul antibody in 100 ul cell suspension, approximately 100,000 cells]; catalog number A121882 antibodies.com [animal] monoclonal, RRID:AB_2876721) for 30 min at 4°C before flow cytometry was performed. Samples were processed using a LSRII flow cytometer (Becton Dickinson) with approximately 100,000 cells per sample and the data was analysed using FlowJo (Version 10, Becton Dickinson) software (open access alternatives include Flowing Software, FCSalyzer and, for those with more experience with R, the FlowCore and FlowJoWrappers R packages). Analysis of the FS and SS parameters was used to gate single cells, excluding both cellular debris and doublet cells. Additionally, a Red 633 laser was used to excite conjugated APC fluorophore, with the resultant emission detected in the red 660/20 channel. The fluorescence intensity of each cell detected was recorded and used to calculate the mean fluorescence intensity (MFI) for OX-5 core and OX-5 edge cells using FloJo analysis software. For each experiment, identical gating and analysis parameters were applied to each experimental condition to avoid bias.\n\nBulk RNA sequencing (RNAseq) was used to profile any further potential transcriptomic differences between resected and residual OX-5 GSCs at scale. GSCs were seeded at a density of 50×105 cells into Matrigel™-coated 10 cm dishes in complete stem media (see Table 5) and incubated for 48 hours at 37°C, 5% CO2, 21% O2 to allow for growth and adhesion. All media was then aspirated before 2 washes were completed with ice cold PBS and the resulting monolayers were then immediately frozen at -80°C until RNA extraction. Three biological replicates were prepared using cells at consecutive passages. RNA was extracted from core and edge GSCs using the Quick-DNA/RNA™ Miniprep Kit (Zymo Research) following the manufacturers protocol. Subsequently, a NanoDrop ND 1000 Spectrophotometer (NanoDrop Technologies) was used to quantify RNA and confirm sample purity (OD260/280 ratios >1.8). Samples were further analysed for RNA integrity using a Eukaryote Total RNA Nano-chip with the Agilent Bioanalyzer 2100 to ensure the samples met the parameters given by the RNA sequencing vendor Novogene (Total RNA extracts at concentrations of ≥ 0.8μg total RNA with extract concentrations of ≥ 20 ng/μl, with volumes of ≥ 20 μl or greater and RNA Integrity Number (RIN) of ≥ 6.8 or more per sample). Sample QC, library preparation and transcriptome sequencing was completed by Novogene (Cambridge, UK) with an aim of 10 million reads per-sample using an Illumina PE150. Raw sequencing reads (fastq) were processed using the nf-core RNA-seq pipline (nf-core/rnaseq) workflow - version 3.8.1. This includes pre-alignment quality control of counts and GC content via FastQC and identification, and removal of adapter sequences using Cutadapt.32 All sample reads were aligned to the reference genome Homo Sapiens GRC38 and transcript-level counts produced using the Salmon tool.33 The transcript-level were aggregated to the gene-level using the tximport R package.34 Principal component analysis (PCA) and differential expression analysis was conducted using the Bioconductor DESeq2 package35 within R Studio (Boston, MA) for estimation and visualisation of dispersion, Log2 Fold Changes, and -Log10 p-values.35,36 Heatmaps were generated using the pheatmap package in R.37 Volcano plots were generated with the tidyverse ggplot2 package.38 KEGG pathway enrichment analysis of significant genes (adjusted p-value < 0.05) was conducted using the clusterProfiler package39 and the KEGG Pathway database. Gene symbols were converted to Entrez IDs via the bitr function, and the enrichKEGG function was used to identify biological pathways significantly enriched. Outputs from the pathway analysis included count ratio, indicating the number of differentially expressed pathway genes as a proportion of the total number of genes in the pathway, and adjusted p-value (p-adjust).\n\nClonogenic studies were used to establish the feasibility of using OX-5 core and edge GSCs within these commonly used survival assays. GSCs were seeded in triplicate into Matrigel™-coated 6-well plates (2D clonogenics) or Matrigel™-coated Alvetex™ scaffolds in 12-well plates (3D clonogenics), which previous studies suggest may be more clinically predictive,26,40 at a density of 1,000 cells per well in 2 ml complete stem media. Plates were incubated at 37°C in 5% CO2 for 21 days prior to staining and counting. For 2D clonogenics, media was removed and colonies were stained using 0.4% methylene blue (Sigma-Aldrich) with a 60 minute incubation at room temperature before methylene blue was removed and any excess was washed from the plates by gentle submersion in tepid tap water. The colonies (greater than 50 cells) were counted. In contrast, 3D clonogenics were stained using 200 μL/well of MTT reagent (Sigma - 10 mg/ml in PBS) added to plates which were then incubated for 4 hours at 37°C in the dark. Importantly, in 3D clonogenic studies, MTT is used only to provide colony specific staining (since methylene blue can also discolour the Alvetex™ scaffolds) and the purple formazan product is not solubilised to estimate cellular activity or viability. Subsequently, media with MTT was aspirated off the scaffolds, plastic 12-well plate clips were removed, and 100 μL/well of 4% paraformaldehyde was added. Plates were incubated at room temperature for 15 minutes to allow fixation of the colonies, before removal of the excess paraformaldehyde. Plates with stained colonies can be foil wrapped and stored at 4°C for up to 14 days, but here were counted within 72 hours. The plating efficiency (PE) for clonogenic studies was calculated by the average number of colonies counted divided by the number of cells plated.\n\nAll in vitro experimental procedures consisted of at least 3 independent biological repeats (containing multiple replicates per group where specified). No formal power calculations were performed as this is a proof of concept, small-scale study and the applicability of the results is limited to the GSC model (and associated patient) in the study. If we were to conduct a larger study, formal sample size estimation would have been performed using a power calculation. Tests of normality (e.g. Shapiro-Wilk) were used to assess generated data sets prior to inferential statistics to confirm differences between test and control groups using appropriate statistical tests such as Mann-Whitney U-test (if normality was not apparent) or Student’s t-test (if normality was apparent) as specified in the results, with p-values <0.05 used to determine statistically significant biological differences while accounting for multiple testing where required. Inferential statistical analysis was performed using GraphPad Prism (Version 7), except where otherwise specified.\n\n\nResults\n\nHere we present results generated using ‘OX-5 core’ GSCs and ‘OX-5 edge’ GSCs, some of the earliest resected and resected models within the SLB we have derived using the Sheffield Protocol detailed above, as a proof of concept. Since glioblastoma exhibit intractable therapeutic resistance and are universally fatal, we hypothesised that GSC lines generated from the infiltrative tumour edge within en bloc specimens to reflect post-surgical residual (normally 'left behind’) disease would demonstrate differences in mRNA expression of putative stem cell markers – since these are associated with resistance to radiotherapy,9 chemotherapy,41 and rapid tumour repopulation following treatment.10 If validated, this hypothesis would, at least in part, explain the failure of promising therapies evaluated in preclinical studies using glioblastoma cell lines generated from typically resected tumour cells to translate to improved patient survival in clinical trials, as the residual cells left behind after surgery (not the resected cells) are responsible for disease progression and death. Therefore, the question of whether resected cells and typically left behind (residual) cells are equivalent is of paramount translational importance.\n\nFirstly, we assessed the mRNA expression of nestin in OX-5 core and OX-5 edge GSCs and matched bulk cultures (propagated in culture media containing serum for 5+ passages), alongside a more commonly used primary, patient-derived glioblastoma line (G1 GSCs and bulk cells).42,43 As expected, OX-5 core, OX-5 edge and G1 GSCs demonstrated greater nestin mRNA expression compared to matched bulk cell (non-GSC enriched) populations (p<0.0001) – see Figure 2A. In contrast, there was no demonstrable divergence in nestin mRNA expression between OX-5 edge GSCs and OX-5 core GSCs (p=0.9556). Similarly, there was no significant difference in nestin mRNA expression between OX-5 edge bulk and OX-5 core bulk cells (p=0.1070). Interestingly however, OX-5 core and OX-5 edge demonstrated higher nestin expression than G1 primary cells in both stem and bulk conditions. This may reflect the early passage nature of OX-5 cells used and/or interpatient variability, but nevertheless confirms expression of the stemness marker nestin in OX-5 core and edge compares well with a typical patient-derived GSC line used in recent studies.42,43\n\nA. TaqMan™ RT-PCR analysis of nestin in untreated OX-5 core and OX-5 edge GSCs with matched bulk populations, to reflect resected and typically residual disease, respectively. These were evaluated for stem cell marker mRNA expression alongside G1 GSCs with matched bulk populations. Nestin expression normalised to HCT116 (colorectal cancer) cell line to facilitate comparison across cell lines and highlight elevated nestin expression across all the primary glioblastoma lines relative to an established non-glioma cell line. Asterisks (*/*/*) denote statistical significance of nestin expression in bulk cells compared to the corresponding GSC line. B. TaqMan™ RT-PCR analysis of CD133, SOX2 and nestin in untreated OX-5 core and OX-5 edge GSCs. Asterisks (*) denote statistical significance of stem cell marker mRNA expression in edge (residual model) stem cells compared to core (resected model) stem cells. In all experiments (A-B) cells were plated then incubated for 24 hours prior to RNA extraction. C. Immunoblot of glioblastoma stem cell marker expression in OX-5 core and OX-5 edge cells. D. Representative immunofluorescence images. E. Flow cytometric analysis of CD133 expression with representative histogram (inset). All graphs shown represent the mean of 3 independent experiments. Error bars represent the SEM.\n\nSubsequently, we investigated expression of the additional commonly used glioblastoma stem cell markers CD133 and SOX2 in OX-5 GSCs, in addition to reassessing the expression of nestin. Validating the previous assessment, both OX-5 edge GSCs and OX-5 core GSCs demonstrated equivalent levels of nestin mRNA expression. However, in contrast, OX-5 edge GSCs demonstrated higher expression of SOX2 mRNA (1.6-fold higher, p=0.0274) and profoundly higher mRNA expression of the archetypal GSC marker CD13312 (9.7-fold higher, p=0.0033) relative to core GSCs from the same patient (Figure 2B). Subsequently, elevated SOX2 and CD133 expression in OX-5 edge GSCs was confirmed at the protein level using immunoblotting, immunofluorescence and flow cytometry (Figure 2C-E). Importantly, substantially higher CD133 protein expression (5.3-fold, p=0.0051) in OX-5 edge GSCs was demonstrated on flow cytometric analyses (Figure 2E), consistent with the profoundly elevated mRNA expression noted in these cells (above). These findings strongly support the possibility that infiltrative GSCs typically left behind after surgery may exhibit a distinct profile of ‘stemness’ and associated inherent therapeutic resistance compared to cells normally resected (and used in laboratory-based research). This hypothesis would be consistent with previous data demonstrating that GSCs demonstrated elevated potential for brain invasion44 and the landmark study by Bao et al. (2006)9 which demonstrated that GSCs, designated on the basis of CD133 positivity, displayed enhanced radioresistance associated with increased expression and activation of key DDR proteins including ATM, CHK2 and CHK1. Further detailed analysis of DDR capacity and activity within a wide range of residual and resected glioblastoma models within the SLB is ongoing in our laboratory and will be reported on in due course.\n\nTo elucidate more holistically whether these resected model and residual models generated in parallel from the same patient represent distinct tumour subpopulations, we characterised the transcriptomic landscapes of both OX-5 core vs edge GSCs using RNA-seq. Principal component analysis (PCA) of these data demonstrates that OX-5 core and edge GSCs differ vastly in the first principal component axis (PC1; Figure 3A). Furthermore, whereas OX-5 core GSCs exhibited a degree of transcriptional variability in principal component 2 (PC2) between independent biological repeats performed at consecutive passages (repeat 1 = passage 6; repeat 2 = passage 7; repeat 3 = passage 8), OX-5 edge GSCs clustered together, potentially indicating that residual (edge) GSCs may represent a more stable, consistent model to work with over time. However, it is important to emphasise that in multi-dimensional scaling the differences in PC2 are deemed of lower importance than differences identified in PC1. Therefore, the global transcriptomic divergence identified between OX-5 core and edge GSCs is more extensive than any divergence within either core or edge GSCs separated by time.\n\nA. Principal component analysis (PCA) of RNAseq data from untreated OX-5 core and OX-5 edge GSCs, to reflect resected and typically residual disease, respectively. B. Volcano plot illustrating genes significantly (adjusted p-value <0.05) upregulated in resected (blue) and residual (green) disease GSCs. C-D. Pathway analysis to demonstrating top 10 KEGG pathways enriched in resected (blue) and residual (green) disease GSCs. All RNA seq data generated using 3 independent biological replicates/samples from GSCs at consecutive passages (for each independent biological sample there was one technical replicate i.e. each of the three samples per GSC line was sequenced once).\n\nFurther analysis of differentially expressed genes (DEGs) emphasised the magnitude of transcriptional divergence between these resected and residual models with 5,815 genes significantly more highly expressed in OX-5 core, whilst 1,773 genes were significantly more highly expressed in OX-5 edge. Genes with the most significant upregulation in OX-5 core GSCs included the transcriptional regulator nuclear protein (NUPR1), which roles include co-ordination of responses to cellular stress including oxidative stress45 and repression of ferroptosis,46 and genes with roles in shaping structural integrity and cell-to-cell interactions including PHLDB2, KRT18 (keratin 18), ITGA2 (integrin subunit alpha 2) and PCDH19 (protocadherin 19). In contrast, OX-5 edge GSCs demonstrated high expression of genes with implications for brain invasion and glioma-neuronal interactions including the matrix metalloproteinase ADAMTS, and SOX8, PMP2 and SEMA3C which have roles in differentiation towards astrocytic and oligodendrocytic lineages,47,48 axonal myelination,49 and axonal guidance,50 respectively (Figure 3B). These data were also consistent with gene ontology/pathway analyses with those most significantly enriched in OX-5 core GSCs including ‘biosynthesis of amino acids’ and ‘HIF-1 signalling pathway’, whilst those most significantly enriched in OX-5 edge GSCs included ‘axon guidance’ and ‘dopaminergic synapse’ pathways (Figure 3C-D). Collectively, these proof of concept data suggest resected (core) and residual (distant invasive edge) GSCs occupy highly distinct transcriptomic landscapes, which are likely to impact spatially-mediated functional heterogeneity and influence therapeutic response.\n\nThe clonogenic survival assay is recognised as a gold standard, clinically-relevant method for determining the sensitivity of cell cultures to candidate therapeutic agents including chemotherapy and ionising radiation. The assay measures viable cells that have demonstrated functional survival by maintaining the propensity for at least 5-6 rounds of replication to produce a colony.51,52 Interestingly, on assessment of clonogenicity, very early passage OX-5 core and OX-5 edge GSCs exhibited poor plating efficiency in 2D culture conditions despite extensive cell proliferation. This appeared largely due to an extremely migratory phenotype, with brightfield microscopy of 2D plates at the end of the colony formation period often demonstrating diffuse cell monolayers (data not shown). However, application of these resected and residual GSCs within a customised 3D Alvetex™ culture system, which as previously been validated to recapitulate key histological features of glioblastoma and better predict treatment response in clinical trials relative to traditional 2D cultures,26,27,40 demonstrated much improved clonogenicity (Figure 4) with a 3.4-fold increase in plating efficiency of 3D OX-5 core (p<0.0001) and a 2.1-fold increase in OX-5 edge GSCs (p=0.0008), relative to 2D conditions. Therefore, the use of resected and residual GSCs within the 3D Alvetex™ culture system may provide a robust and accessible platform to future studies to assess the influence of spatial intratumoural heterogeneity in differential responses to therapy in the preclinical setting.\n\nUntreated OX-5 core and OX-5 edge GSCs, to reflect resected and typically residual disease, were seeded at a density of 1,000 cells per well in 2D or 3D culture conditions (as indicated) then incubated for 21 days. Subsequently, colonies were identified using 0.04% methylene blue in 100% methanol to stain and fix 2D colonies, or incubation with MTT for 4 hours to reveal 3D colonies followed by paraformaldehyde fixation prior to quantification. A. Representative images, and; B. Comparison of clonogenic plating efficiency for OX-5 core and OX-5 edge GSCs in 2D and 3D Alvetex™ scaffold-based conditions. Data points shown represent the mean of 3 independent experiments (for each independent experiment there were 3 technical replicates for each condition). Error bars represent the SEM. Note 2D and 3D clonogenic plates not to scale – internal diameter of wells in 2D (6-well) plates is 2.3-fold the diameter of 3D Alvetex™ scaffolds (34.8 mm vs 15 mm).\n\n\nDiscussion\n\nDespite increasing evidence that intratumoural heterogeneity represents a major contributor to therapeutic resistance in glioblastoma,17–19 the availability of both in vitro and animal models systems that meaningfully recapitulate spatiofunctional heterogeneity present within patients in the early preclinical setting remains limited. Trends towards increasing use of serum-free protocols to derive and propagate patient-derived glioblastoma cells53–55 for over a decade have played a crucial role in advancing our understanding of inherently treatment resistant GSC subpopulations within tumours. However, it is becoming increasingly clear that not all GSC subpopulations are functionally equivalent56,57 and as such, there is a clear need to define anatomic or spatial variations in treatment response and/or resistance mechanisms. Indeed, an important study by Spiteri et al. (2018),18 which incorporated fluorescence-guided sampling of more distant infiltrative and subventricular zone glioblastoma cells, supports a hypothesis of genetically distinct tumour subclones that arise early in the evolution of glioblastoma; demonstrating a greater functional capacity to invade deeper into normal brain and therefore be more likely to represent disease left behind after surgery (residual disease).58,59 Since established cell and patient-derived orthotopic xenograft models commonly used in neuro-oncology research often fail to reflect the brain invasive phenotype of glioblastoma observed in patients,25,60 we have identified a previously unmet need. The replacement of some in vivo studies with the ex vivo residual disease models generated using tumour adjacent infiltrated brain tissue within en bloc tissue specimens from human patients may provide both scientific and 3Rs benefits.\n\nThe parallel ex vivo primary, patient-derived lines developed and presented here build on these prior studies by establishing models suitable to interrogate whether, and how, previously observed intra-tumoural spatial genetic heterogeneity18,61–63 will translate to functional heterogeneity, including intracellular responses to DNA damaging radiotherapy and temozolomide treatments (which represent standard-of-care adjuvant management for patients with glioblastoma) and subclonal divergence in therapeutic sensitivity. Crucially, post-surgical residual disease cannot be considered equivalent to glioblastoma at the time of recurrence, which may harbour a range of genomic changes following chemoradiotherapy.64 We demonstrate for the first time that distant infiltrative GSCs derived from tumour adjacent brain parenchyma within en bloc partial lobectomy specimens exhibit a distinct profile of key glioma stem cell marker mRNA expression (Figure 2), which may have implications for the responsiveness of residual GSC models to current therapy. These results are consistent with the study of glioblastoma tumour organoids by Hubert et al. (2016),65 which identified a higher proportion of SOX2+ cells at the rim of organoids relative to the core. However, our novel pragmatic methodology using rare en bloc partial lobectomy specimens provides the opportunity to interrogate the more distant infiltrative cells taken from patients and contrast these with GSCs from the tumour tissue normally resected in patient-matched way, and thus maximise the chance of defining quantitative differences and qualitative nuances between resected and typically residual disease. Developing a more detailed understanding of treatment naïve post-surgical residual disease, and how this may differ from resected disease (which forms the basis of current glioblastoma models), is likely to provide useful insights and inform more effective treatment of glioblastoma in the newly diagnosed setting.\n\nWork by Smith & Rahman et al. using fluorescence-activated cell sorting of cells from resection margins sampled during 5-ALA fluorescence-guided surgery has provided an important approach to begin investigating the properties of cells more distant from the tumour core.66,67 However, spatially, these cells were based on the anatomical limits of a typical resection, and the isolation of ‘edge’ cells using a metabolism-based marker could potentially bias further investigation of complex divergence between core and edge cells. In contrast, the Sheffield Protocol (Figure 1) generates label-free ex vivo models of resected and post-surgical residual disease through a pragmatic approach which utilises relatively rare en bloc specimens (for example, where resection includes a partial lobectomy) to provide access to the most distant infiltrative cells feasible from a living patient without the need for any marker to select or enrich for a specific subpopulation of cells. These important specimens include portions of infiltrated brain that in most other circumstances would not otherwise be resected, and are large, which likely mitigates against a low proportion of cancerous (or 5-ALA fluorescing) cells at sites distant from the main tumour mass. We therefore suggest that GSCs derived from the most tumour-distant aspect of such samples are representative of bona fide residual disease and their propagation in parallel with GSCs derived from the tumour core can provide a powerful tool to interrogate differences in the complex biology of normally resected disease. These models are distinct from, and complementary to, recent models based on enriching for cells demonstrating 5-ALA induced fluorescence from tissue at the margins of a typical surgical resection.66,67 Considering that only the residual cells left behind after surgery are responsible for disease progression following standard-of-care therapy, developing a comprehensive understanding of residual disease is critical to help design future treatment strategies that account for spatial intratumoural heterogeneity and pre-empt disease recurrence.\n\nFrom a 3Rs perspective, we firstly emphasise that the current translational paradigm for progressing potential therapeutic agents into the clinic typically through a series of in vitro studies using established and/or patient-derived cell cultures generated from the normally resected tumour mass, followed by in vivo studies, most commonly applying orthotopic PDX models through implantation of the same types of cell lines has not served patients with glioblastoma well. This is evidenced by the lack of new regulatory drug approvals since 2005 in the UK (temozolomide) and 2009 in the US (bevacizumab).68 Therefore, the generation and application of patient-derived resected (core) and residual (edge) GSCs cultured within both 2D and 3D models has the potential to replace some murine in vivo studies in high-grade glioma research, particularly in the context of efficacy studies testing drugs that have already progressed through clinical trials for other types of cancers and are therefore known to be clinically-safe/tolerable.\n\nFurthermore, the patient-specific nature of each resected and residual GSC model generated could support replacement of animal studies specifically in the context of murine avatars for testing experimental therapeutics in glioblastoma. However, we do accept that confirmation of the clinically predictive nature of these models though assessing response to standard-of-care therapies in the patient-specific models and comparing this to actual response and survival amongst the associated patient cohort in the clinic would be important to provide definitive validation. This work is currently ongoing within our laboratory. Our ex vivo resected and post-surgical residual disease model advantages over subcutaneous and orthotopic PDX models also include speed of data generation (with robust survival data typically within 3 weeks using our 3D scaffold-based clonogenic assay) and scalability with the ability to test multiple drugs/combinations within a 12-well format and potential to integrate these models into 96-well 3D scaffold-based systems in the future.69 These advantages also highlight our model’s potential for reducing animal usage, as a range of candidate drugs and/or combinations could be effectively triaged prior to in vivo studies, resulting in fewer animals required to establish the most promising therapeutic strategy for clinical translation.\n\nTherefore, given the prevalent use of animals in glioblastoma research globally, estimated to be over 75,600 animals/year based on our analysis of PubMed-indexed publications, we believe resected and residual GSC models have the potential to reduce and/or replace at least 5-10% of animal use (3,780-7,560 animals/year) in the contexts described above. To facilitate this, we are sharing our resected and residual models from within the SLB with researchers at an increasing number of academic institutions both nationally and internationally (see below), and we are actively engaging with our research ethics and Healthcare Gateway teams at the University and Royal Hallamshire Hospital to explore pathways that will enable the use of these models in studies conducted by Commercial partners (including Pharmaceutical Partners) to support residual disease informed drug discovery and evaluation.\n\nAs outlined in this methods paper, the Sheffield Protocol is based on macrodissection of suitable en bloc specimens and requires tight collaboration between clinical and academic members of the research team to ensure appropriate patient selection. Furthermore, a clear anatomical and spatial awareness follows each unique sample from the operating theatre to the bench. In this respect, we find the availability of a surgeon to stay with a sample from resection through to macrodissection into core, intermediate and edge subdivisions to be critically important. We believe that our protocol generates bona fide patient-derived core and infiltrative edge GSC lines in parallel, which exhibit divergent transcriptional landscapes (Figure 2), highly and differentially expressed putative glioblastoma stem cell markers (Figure 3), and can be easily applied to a range of assays and techniques commonly used to investigate cancer biology and assess novel therapeutic interventions, including clonogenic survival assays, immunoblotting, immunofluorescence, RT-qPCR and omic characterisation (Figures 2-4). The protocol is also simple to modify, for example, when a particularly large sample is provided, it is often feasible to generate multiple core and multiple edge GSC lines from the same en bloc specimen radiating out from the tumour core to distal invasive edge (where normal brain white matter can often be visualised). Conversely, when a sample is found to be unsuitable for resected and residual model derivation, we routinely generate between 3-5 parallel GSC lines from different tumour regions to generate ‘random intratumoural heterogeneity models’ which may provide useful additional controls in comparison to residual models in the future (i.e. establishing whether or not any specific divergent feature observed in residual disease models lies within the spectrum of variation observed portended by spatial heterogeneity within the core mass of the tumour).\n\nFurthermore, in resections where the surgical team are able to record the precise retrieval location of some tumour tissue samples using intra-operative neuronavigation, MRI spatially-registered GSC models can be generated to further enhance spatiofunctional understanding. This approach can even be integrated with cases where resected and residual GSC models are generated following removal of the initial en bloc specimen, when the operating surgeon subsequently begins to resect further tumour infiltrated tissue from the posterior resection margin.\n\nUsing a combination of these approaches, our team has been able to generate the Sheffield Living Biobank (SLB) of patient-derived high-grade glioma. To date this includes over 150 models generated from 60+ patients (https://bit.ly/3yFF8WP) to help recapitulate the diverse repertoire of intratumoural and inter-patient heterogeneity observed in the clinic, and replace the need for animal studies in some contexts through the provision of more clinically-relevant cell culture models. SLB includes 44+ resected and residual GSC models and our team is delighted to share these with members of the neuro-oncology research community, as evidenced by our existing Materials Transfer Agreements with UK institutions for research use of SLB models (Figure 5).\n\n(UK map image credit: ELIKA/iStockPhoto).\n\nMTAs have been established with 8 academic partner institutions to-date, with further potential MTAs in discussion with UK and international academic institutions (including in Sweden and South Africa). Work is also underway to facilitate use of these models within research completed by industrial partners. UK map image credit: ELIKA/iStockPhoto.\n\nIn conclusion, we present here a new robust methodology for the generation of surgically-relevant models of resected and residual glioblastoma that can be used to further elucidate the complex biology of these tumours, prevent unnecessary animal studies, and assess novel therapeutic interventions. We hope this can provide some much-needed and long overdue progress towards better treatment options for these patients.\n\n\nEthics and consent\n\nThe procurement of en bloc specimens suitable for resected and residual model generation requires appropriate institutional research ethics. At our institution, all clinical information and specimen acquisition was performed in within the scope of the approved IRB ethics protocol 11-YH-0319 (STH15598) - Yorkshire & The Humber - Leeds East Research Ethics Committee (approved 03/11/2011, substantial amendment approved 01/06/2016) and in adherence to the Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/). Close collaboration across academic and clinical boundaries with input from the neuro-oncology multi-disciplinary team (MDT) is essential.\n\nWritten informed consent for publication of the participants/patients’ anonymised associated clinical information and images was obtained from the patients providing brain tumour tissue for research under NHS REC approval STH15598.\n\n\nAuthor contributions\n\nConceptualization: OR; SJC.\n\nData Curation: OR; CMG; KM; CGJ; KW; STW; MJD.\n\nFormal Analysis: OR; CMG; KM; CGJ; KW; STW; MJD; SJC.\n\nFunding Acquisition: OR; SJC.\n\nInvestigation: OR; CMG; KM; CGJ; KW; STW; AV; AGA; VB; MJD; AC; SS; DAJ; TAC; DW; YAT; SJC.\n\nMethodology: OR; CMG; KM; CGJ; KW; STW; MJD.\n\nProject Administration: OR; SJC.\n\nSupervision: OR; NGR; AJC; YAT; SJC.\n\nValidation: OR; CMG; KM; MJD; SJC.\n\nVisualisation: OR; CMG; KM; KW; MJD.\n\nWriting – Original Draft Preparation: OR; CMG; SJC.\n\nWriting – Review & Editing: OR; CMG; KM; AV; VB; MJD; NGR; SS; DAJ; TAC; AJC; DW; YAT; SJC.",
"appendix": "Data availability\n\nAvailable at Harvard Dataverse –“Ex-vivo models of post-surgical residual disease in human glioblastoma”, https://doi.org/10.7910/DVN/O5KCPY, Harvard Dataverse, V1, UNF:6:GJh1cps1TrVU+56oYX2/Ng== [fileUNF]. 70\n\nThis project contains the following underlying data:\n\n• RT-qPCR OX5 Stem Core vs Edge (Stem Markers)_F1000.xlsx (Spreadsheet containing OX-5 core and edge cells RT-qPCR raw data and analysis).\n\n• RT-qPCR G1 Stem and Bulk (F1000).xlsx (Spreadsheet containing G1 cells RT-qPCR raw data and analysis).\n\n• DESeq_Edge_vs_Core.tab (Spreadsheet containing OX-5 core and edge cells RNAseq data (DE genes)).\n\n• Ox5 Core & Edge Clonogenic Test (F1000).xlsx (Spreadsheet containing OX-5 core and edge cells 2D and 3D clonogenic counts).\n\nData are available under the terms of the Creative Commons CC0 1.0 Universal Public Domain Dedication.\n\n\nAcknowledgements\n\nWe would like to thank neurosurgical theatre staff and members of the neuro-oncology MDT at Sheffield Teaching Hospitals NHS Foundation Trust in addition to: Hazem Abuhusain, Selma Al-Ahmad, Anna Bjornson, Daniel Brown, Matthew Crank, Kishor Choudhari, David Eagle, Ahmed Elbelkasy, Daniel Gatt, Hussain Kandeel, Piravin Kumar Ramakrishnan, Geza Mezei, François Okoroafor, Farouk Olubajo, Jerry Phillips, Stuart Stokes, Shungu Ushewokunze, Adam Wahba, William White and Yap Yoong for their assistance in retrieving surgical resection specimens for resected and residual model development. We also like to thank Professor Colin Watts and Professor Anthony Chalmers for their kind provision of G1 GSCs which were previously generated in Cambridge within Professor Colin Watts’ laboratory and have been used in reports from multiple groups, including our own. 30,53,71\n\n\nReferences\n\nAlexander BM, et al.: Adaptive Global Innovative Learning Environment for Glioblastoma: GBM AGILE. Clin. Cancer Res. 2018; 24: 737–743. PubMed Abstract | Publisher Full Text\n\nInternational Agency for Research on Cancer. 2016. Reference Source\n\nMa R, et al.: Residual enhancing disease after surgery for glioblastoma: evaluation of practice in the United Kingdom. Neurooncol. Pract. 2018; 5: 74–81. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRominiyi O, et al.: Tumour treating fields therapy for glioblastoma: current advances and future directions. Br. J. Cancer. 2021; 124: 697–709. 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}
|
[
{
"id": "340692",
"date": "10 Dec 2024",
"name": "Heiko Wurdak",
"expertise": [
"Reviewer Expertise Stem cell and tumour biology",
"co-reviewed by two neurosurgeons"
],
"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\nRominiyi et al. address residual disease in glioblastoma (GB), an area of unmet clinical need. The use of 5ALA to generate cell lines is a practical approach, and the effort to develop quicker 2D/3D alternatives to patient-derived xenograft (PDX) models is well-placed, given the limitations of PDX models (e.g., time and resources). The establishment of a large cohort of patient-derived cell lines, coupled with a commitment to share these via material transfer agreements (MTAs), is a valuable contribution to the field. This resource has clear potential to support further research, particularly if validated through collaborative studies (e.g., an updated list of publications utilising this resource would further underscore its impact). Major Points\nThe study lacks evidence that the model represents GB cases overall, as many GBs do not permit en bloc resection. Targeted biopsies from the edge and centre of tumours where en bloc resection is infeasible could address this gap. The rationale for prioritising en bloc sampling over individual bulk or core samples is unclear, particularly when the downstream application involves glioma stem cell culture from dissociated tissue. Additionally, it remains uncertain whether gliomatosis (considered a GB subtype) is represented in the model/resource? While the protocol appears robust, the methods employed, from tissue dissociation to spheroid culture and marker use, are not inherently innovative. The emphasis should shift to highlighting the high quality of the resource rather than overstating methodological innovation. The necrotic nature of GB centre tissue presents challenges that are not addressed. The study should clarify how viable GCSs were obtained and validated from such regions. Peripheral samples, which become increasingly \"normal\" as their distance from the tumour increases, require a more detailed explanation of their identification and validation. Differences in the tumour microenvironment (TME) between the periphery and the edge should be explored, along with their reciprocal influences. Supra-marginal resection is presented as capturing residual cell populations but is only feasible for a limited subset of patients, introducing selection bias. Long-term utility could be enhanced by including longitudinal data comparing centre and edge samples pre- and post-treatment. The limitations of the model/resource should explicitly acknowledge the absence of an immune system. The focus on PDX model drawbacks overlooks syngeneic and genetic mouse models, which are immunocompetent and better mimic patient pathways and residual cell populations. These models should be included in the narrative to clarify how the proposed protocol complements existing approaches.\nMinor Points\nThe reliance on CD133 as a single marker for glioblastoma stem cells (GSCs) may be insufficient. Co-labelling with additional markers (e.g., SOX2, OLIG2, TRRAP, SSEA4) could improve robustness. Differential treatment responses (e.g., to temozolomide and radiotherapy) between core and edge samples are not demonstrated but would have strengthened the conclusions. The study would benefit from referencing advancements such as label-free optical microscopy (e.g., FastGlioma), which is gaining traction in the field of \"edge surgery.\" Figures could be improved by adding scale bars to all relevant panels, including Figure 1B. A graphical overview in Figure 1 linking tissue harvesting approaches to parallel and/or longitudinal biological characterisation methods and endpoint readouts would improve accessibility. The statistical section should describe all test parameters and underlying statistical assumptions for mRNA-seq analysis in greater detail. Transparency would be enhanced by depositing bulk mRNA-seq data in a repository such as GEO. The absence of single-cell mRNA-seq data limits the study’s ability to address tumour plasticity over time. This limitation should be discussed in relation to existing literature (e.g., LeBlanc, Cancer Cell, 2022).\nOverall, the protocol could be contextualised further by addressing how the methodology might adapt to advancements in the surgical field and evolving model utility over time.\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? 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? Yes",
"responses": []
},
{
"id": "340699",
"date": "17 Dec 2024",
"name": "Karin Purshouse",
"expertise": [
"Reviewer Expertise I am a clinician scientist who studies glioblastoma stem cells",
"specifically gene regulation of stem cell-like GBM cells",
"and has experience of primary GBM cell culture and associated in vitro experiments. I work in both a clinical setting (medical oncology) and research setting (as above)."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper describes the methodology for the Sheffield Protocol, whereby the authors have generated a library of primary resected and residual GBM cell cultures. These have been characterised and made available in a large academic repository of 150 GSC cell lines, which is of significant value to the GBM research community. The authors have clearly described the multidisciplinary team that were coordinated to generate this resource, and provide real-world insights for others looking to reproduce their work.\n\nNotes on study justification: The authors rightly make the case for reducing and rationalising animal use in GBM research. However it is important to note that many of the assumptions regarding the inferiority of mouse PDX models may be driven by historical examples of inappropriate cells used for implantation rather than the mouse model itself. For example, U87 cells are not histologically invasive, and indeed lack many of the features of GBM. More recent examples with primary patient-derived cells suggest these are a biologically relevant model, capturing the invasive and genomic phenotype. For example, deCarvalho et al (2018) suggested good molecular concordance between primary neuro-cultures from patients and mouse-derived xenografts. This is important because, while there are many justifications for reducing the use of mice in this setting, they remain a vital pre-clinical model – including for those cell cultures derived in this study. Could the text be updated to reflect this? Notes on method: The authors do not use laminin in their methodology, despite being the cited and widely used cell culture method for GSCs (Pollard et al, 2009), and instead use Matrigel. In the paper by Pollard et al, it is suggested that cell clumping is more common with gelatin or untreated plastic. Could the authors suggest the impact of Matrigel vs laminin? This is notable given that the authors outline colony survival assays as being possible with these cells (albeit in 3D), which others have found to be technically/temporally challenging with GSCs. Is there a chance these cells, including in CSA, behave differently in this culture media vs a traditional NSC culture media? The proposal of a 3D CSA methodology that is adaptable for cells where 2D CSA is ineffective is a valuable contribution to the field. Could the authors provide further rationale behind serum ‘bulk’ tumour derivation– how does this reflect the clinical picture, given that in-situ tumours are not exposed to serum, and what hypotheses does this address? In GBM cell lines (U87, U251) that are grown in serum-containing media, serum is likely to drive cells away stem cell pathway towards a differentiated astrocytic state – if this is the intended hypothesis, it would be useful for this to be clarified.\n\nNotes on findings: The primary novelty of this study is in defining cells in resected brain vs the tumour itself, and in doing so creating a resource for the community for further study. The authors identify a greater stem-ness phenotype in residual vs resected tumour cells, highlighting the importance of a stem-cell-like phenotype of GBM cells that has been previously reported as being critical to the invasive nature of GBM. Their methodology highlights that stem-cell-like cells drive recurrence, and that these cells remain following tumour resection. They also demonstrate that these harbour a distinct transcriptomic profile vs resected tumour. While it would be interesting for further results regarding this to be presented, the authors make their future and ongoing work clear in the text. Overall this study makes a significant contribution to the GBM community by creating the SLB as a resource. The methods are clearly described in such a way as to make them reproducible. There are some queries around the methodology, such as the choice to deviate from a well-established GSC culture protocol. Further clarification of these culture conditions would be useful. Understanding the profile of invasive GBM cells found in residual brain tissue is a key and novel contribution to the GBM research landscape, and will clearly form an important body of onward work.\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": []
}
] | 1
|
https://f1000research.com/articles/13-1316
|
https://f1000research.com/articles/13-6/v1
|
03 Jan 24
|
{
"type": "Research Article",
"title": "An international, cross-sectional survey of preprint attitudes among biomedical researchers",
"authors": [
"Jeremy Y. Ng",
"Valerie Chow",
"Lucas J. Santoro",
"Anna Catharina Vieira Armond",
"Sanam Ebrahimzadeh Pirshahid",
"Kelly D. Cobey",
"David Moher",
"Valerie Chow",
"Lucas J. Santoro",
"Anna Catharina Vieira Armond",
"Sanam Ebrahimzadeh Pirshahid",
"Kelly D. Cobey",
"David Moher"
],
"abstract": "Background Preprints are scientific manuscripts that are made available on open-access servers but are not yet peer reviewed. Although preprints are becoming more prevalent, uptake is not uniform or optimal. Understanding researchers’ opinions and attitudes toward preprints is valuable for their successful implementation. Understanding knowledge gaps and researchers’ attitudes toward preprinting can assist stakeholders, such as journals, funding agencies, and universities, to implement preprints more effectively. Here, we aimed to collect perceptions and behaviours regarding preprints across an international sample of biomedical researchers.\n\nMethods Biomedical authors were identified by a keyword-based, systematic search of the MEDLINE database, and their emails were extracted to invite them to our survey. A cross-sectional anonymous survey was distributed to all identified biomedical authors to collect their knowledge, attitudes, and opinions regarding preprinting.\n\nResults The survey was completed by 730 biomedical researchers with a response rate of 3.20% and demonstrated a wide range of attitudes and opinions about preprints with authors from various disciplines and career stages worldwide. Most respondents were familiar with the concept of preprints but most had not previously published a preprint. The lead author of the project and journal policy had the greatest impact on decisions to post a preprint, whereas employers/research institutes had the least impact. Supporting open science practices was the highest ranked incentive, while increasing authors’ visibility was the highest ranked motivation for publishing preprints.\n\nConclusions Although many biomedical researchers recognize the benefits of preprints, there is still hesitation among others to engage in this practice. This may be due to the general lack of peer review of preprints and little enthusiasm from external organizations such as journals, funding agencies, and universities. Future work is needed to determine optimal ways to increase researchers’ attitudes through modifications to current preprint systems and policies.",
"keywords": [
"biomedicine",
"open science",
"open science practices",
"preprinting",
"preprints",
"researchers"
],
"content": "Introduction\n\nThe term “preprints” refers to scientific manuscripts that are made available on an open-access infrastructure, known as the “preprint server,” which has not yet undergone formal peer review1 (https://asapbio.org/). One of the primary purposes of preprints is to make research available as quickly as possible, given the time lag from journal submission to publication, which typically takes around 8 to 10 months in biomedical sciences due to multiple review rounds, editorial decision-making, high rejection rates, and time needed for revisions.1–5 Preprints do not rely on peer review prior to release, allowing knowledge to be shared quickly with the introduction of novel results and methodology that can save months to years of research time.4 Preprints have become incredibly valuable for authors, as a larger group of researchers can critique their work (i.e., open peer review) with the preprint servers’ feedback system that allows for public and open feedback directly onto a manuscript that encourages discussion (https://asapbio.org/). The focused, appropriate, specific, and transparent (FAST) principles, which are guidelines that reviewers can follow when reviewing preprints, allow for high-quality, constructive feedback to be provided.6 As a result, researchers can improve their final manuscript, so it can possibly be published sooner and with fewer revisions.2 In addition, authors have also begun to cite preprints more frequently in their working manuscripts as institutions and funders have become more open and permissible in their policies regarding preprints.2 Furthermore, funders acknowledge the importance of preprints by encouraging researchers to post and reference preprints in their grant applications.2 Preprint servers still utilize a minimal screening process to evaluate articles for incompleteness, plagiarism, and whether they blatantly disregard or contradict widely accepted medical practices that could potentially jeopardize someone’s health if posted.7\n\nHowever, despite their benefits, many scientists are hesitant about preprinting. Major concerns include the credibility of preprints and premature media coverage.2,5,8 During the COVID-19 pandemic, online media used preprints to rapidly introduce novel research to the public. However, patients and the public may be less familiar with the fact that preprints have not yet undergone the peer review process and may fail to discern the difference between a preprint and an article published in peer reviewed literature.2,8 Nonetheless, much COVID-19 research posted on preprint servers has received high levels of coverage, and certain preprints could be used to push certain agendas, such as conspiracy theories and xenophobia.8 This has led to the spread of misinformation.8,9\n\nThe purpose of this study was to explore biomedical researchers’ attitudes toward preprinting through the administration of an anonymous cross-sectional online survey. We aimed to determine the factors that influence biomedical researchers’ opinions about publishing and viewing preprints. Thus, future work should focus on determining how to improve researchers’ attitudes toward preprinting. Additionally, our results may potentially impact how other stakeholders implement and modify their preprint policies in the future.\n\n\nMethods\n\nPrior to commencing this study, a protocol was registered in the Open Science Framework (OSF) before participant recruiting began.10 The MEDLINE database was used to identify participants using publicly available information. Once identified, the participants were invited to complete an online survey. Survey questions were purpose-built by a core team of authors. They focused on understanding biomedical researchers’ attitudes and opinions concerning preprinting. This study was approved by the Ottawa Health Sciences Research Ethics Board (OHSN-REB Number: 20220584-01H) on November 17, 2022.\n\nThe protocol, study materials, and raw and analyzed data have been made available via OSF at the time of publication submission.10 A preprint of our manuscript has been posted on MedRxiv.\n\nWe conducted an anonymous, online, cross-sectional, closed survey of authors published in biomedical journals.\n\nThe sampling method followed that described by Ebrahimzadeh et al.11 We downloaded the MEDLINE database that contained approximately 30,000 journals. From this list, 400 journals were randomly selected using the RAND() function of Microsoft Excel for Microsoft 365 MSO (Version 2310 Build 16.0.16924.20054) (2021). Authors’ names and emails were extracted using our script from articles published from 2021/07/01 to 2022/08/01. Extended data: Supplementary File 1 outlines the semi-automated process we used, generated by Ebrahimzadeh et al.11,12\n\nOnly researchers who were identified by our sampling framework developed by Ebrahimzadeh et al.11 received a closed survey. Using SurveyMonkey, the prospective participants received an email invitation to complete the survey. The email included an authorized recruitment script that described the study and its goals, invited recipients to review an informed consent form, and asked them to complete an anonymous online survey. Upon clicking on the survey link in the invitation email, participants had to read and agree with the informed consent form before being able to see the survey. The initial list of 24 000 names and e-mails of the corresponding authors contained duplicates and no longer functioning e-mails. We were able to determine that functioning emails were no longer available due to SurveyMonkey’s bounced function, which labels certain contact information that has a permanent reason for an email or text to not be delivered. Before recruitment, duplicate authors and no longer functioning emails were deleted from the dataset. Therefore, 22 808 corresponding authors were emailed. We predicted that we would receive approximately 2200 responses based on a predicted response rate of approximately 10%. There was no financial compensation or requirements for participation. Anyone who did not want to respond to a question could skip it.\n\nThe complete survey is provided in the Extended data: Supplementary File 2.12 The survey was created, pilot tested by SEP, DM, KC, and ACA, distributed, and collected using the University of Ottawa’s SurveyMonkey account. The survey contained 29 questions, and SurveyMonkey estimated that it would take approximately 15 minutes to complete. The survey initially asked participants five general demographic questions including gender, research role, area of research, and country of residence. They were then asked nine questions about their experiences with preprints and fifteen questions about their preferences and opinions regarding preprinting. The survey used adaptive formatting, which means that each participant’s prior response influences the next question they see and the answers that might be provided. Most of the questions were multiple-choice; the remaining questions were open-ended and required participants to write their responses in a text box. Reminder emails were sent to the participants after the first and second weeks following the original invitation. The survey was closed approximately five weeks after the initial invitation email was sent. Both the initial invitation and reminder emails made this clear to the survey takers. Responses were collected from January to February 2023.\n\nIn accordance with Ebrahimzadeh et al.,11 survey data gathered from the participants were exported to Microsoft Excel. Basic descriptive statistics, such as counts and percentages, were generated based on the analysis of the quantitative data. Based on gender, employment sector, current career stage, and research area, information and replies from participants were compared and studied. Thematic content analysis was used by different members of the research team to individually code replies to specific qualitative items. To reach an agreement on the respective codes, which are categorically classified and specified into distinct tables, researchers carried out multiple rounds of discussions. The Checklist for Reporting Results of Internet E-Surveys (CHERRIES) was used to report this survey.13\n\n\nResults\n\nOur survey received 730 responses, with a response rate of 3.20% and a completion rate of 95.48%. Incomplete responses were defined as those with no questions answered on the second page of the survey. Moreover, we have reported our raw response rate, which is underestimated because we cannot determine how many of the 22 808 authors who were emailed identified as biomedical researchers or had an actively working email address. All questions were optional; therefore, we provided the total number of respondents for each question. The percentages provided were appropriately calculated using each question’s total number of responses. Over three-fifths of respondents (n=455, 62.41%) were identified as senior researchers, which we defined as researchers who started their careers after formal education over ten years ago. Of the 729 responses, participants were identified as follows: academia (n=580, 79.56%), research staff with no formal academic or industry position (n=58, 7.96%), government scientists (n=28, 3.84%), third sector (n=8, 1.10%), pharmaceutical industry (n=5, 0.69%), and none of the participants were part of the scholarly communication industry. We received 50 responses (6.86%) that chose the “other” option, which mainly consisted of participants from the biotechnology industry, retired personnel, clinical researchers, clinicians, medical practitioners, and students. Detailed demographics and other aggregate participant data are presented in Table 1. The responses from participants were also categorized based on gender, employment sector, current career stage, and research area.\n\n* Total number of countries with one response.\n\nFamiliarity with preprints\n\nWe asked how familiar the participants were with the concept of a preprint based on the given definition, “A publicly available version of any type of scientific manuscript/research output preceding formal publication” (https://forrt.org/). Of the 694 responses, participants ranked how familiar they were with the concept of preprints: very familiar (n=167, 24.06%), familiar (n=269, 38.76%), and somewhat familiar (n=92, 13.26%). Only 61 (8.79%) respondents had never heard of this term.\n\nPublishing experience\n\nWe then asked about the participants’ personal experiences with posting on preprint servers. Of the 694 responses, approximately one-third (n=237, 34.15%) had authored more than 31 publications in the past five years. Most participants had not posted a manuscript on a preprint server, with 540 (78.15%) participants of 691 responses not posting their most recent work on a preprint server, and 414 (59.74%) respondents of 693 responses having never posted a manuscript on a preprint server. However, when asked if participants would create a preprint in the future, we received 695 responses: 303 (43.60%) participants said they would not, 296 (42.59%) participants said they were unsure if they would, and 96 (13.81%) participants said they would create a preprint in the future.\n\nOf the 335 respondents who had posted preprints before, the most common preprint server used was bioRxiv, with 148 (44.18%) respondents having published previously on this server. In addition, we asked at what point in the publication process were preprints posted, and of the 294 respondents who had previously posted preprints, 110 (37.41%) participants submitted their manuscripts prior to submitting them to a journal, while 133 (45.24%) participants posted a preprint simultaneously while submitting to a journal.\n\nViewing/downloading preprints\n\nInterestingly, although most participants did not publish their own works on preprint servers, more than two-thirds of the 695 respondents (n=481, 69.21%) had previously viewed or downloaded preprints, although only approximately a quarter (n=176, 25.32%) had cited a preprint. The most common preprint servers used to view/download preprints among 682 responses were bioRxiv (n=243, 35.63%), MedRxiv (n=148, 21.70%), and ResearchGate (n=140, 20.53%).\n\nPeer reviewing preprints\n\nWe asked whether peer review should become a part of the preprinting process, and 684 responded, with 231 (33.77%) respondents believing that peer review should be part of the preprinting process, 240 (35.09%) respondents said it should not, while 213 respondents (31.14%) were unsure (Table 2). We also asked if our participants had experience with peer reviewing a preprint, and from the 688 responses, the vast majority (n=638, 92.73%) stated they had not. Of those who had peer reviewed a preprint, we wanted to know if the FAST principles were used during the process, and we received 205 responses. Of the respondents, 148 (72.20%) stated that they were not familiar with the FAST principles, 44 (21.46%) said they did not use the FAST principles, and 13 (6.34%) said they did.\n\nWe also asked if participants believed that patients or members of the public should be able to peer review preprints. Of the 445 who expressed an opinion, 320 (71.91%) believed that patients and members of the public should not be able to peer review preprints, while 125 (28.09%) believed that they should be able to.\n\nWe then aimed to determine the factors that impact an author’s decision to post a preprint. We asked participants to assess which had the most significant impact on posting a preprint: employer/research institution, funding agency, lead author, co-author consensus, and journal policy. From the 651 respondents, the lead author had the most significant impact on the decision of posting a preprint, followed by journal policy, co-author consensus, funding agency, and the least impactful is the employer/research institution (Figure 1).\n\nWe also asked whether employers required or prohibited the posting of a preprint prior to submission to a journal. Most employers did not, with 649/690 (94.06%) respondents stating that their employer did not require them to post a preprint, and 657/691 (95.08%) respondents stating that employers do not prohibit them from doing so. In addition, we wanted to see if a funder may impact this decision, and 639/692 (92.34%) participants stated that funders do not require them to post a preprint.\n\nWe also wanted to determine how familiar participants were with the preprint policies of journals that they had experience of publishing in. First, we asked whether participants were familiar with either Sherpa Romeo or Transpose Publishing, which are resources that present the preprint policies of most peer reviewed journals. Of the 686 responses, 623 (90.95%) were not familiar with Sherpa Romeo, and 656 (95.91%) were not familiar with Transpose Publishing. In addition, we asked what the preprint policy was for the journals of respondents’ most recent first author/co-author publications (Figure 2). Of the 684 responses, 282 (41.23%) stated that they were not familiar with the preprint policies, while 183 (26.75%) stated that preprinting was permitted. Only 34 (4.97%) respondents and 61 (8.92%) respondents stated that preprinting was prohibited or that they had no preprinting policies, respectively.\n\nRespondents were asked to what extent they agreed with certain incentives or the consequences of preprinting (Figure 3). Of the 666 who answered, over half had positive attitudes toward the following incentives and consequences: 1) Preprints support open science practices (n=456, 68.99%); 2) Preprints should not be cited because they may contain results that lack credibility because they had not yet undergone peer review (n=433, 65.12%); 3) Preprints can be used as a weapon for the dissemination of misinformation (n=417, 62.61%); 4) Preprinting behaviors will increase in the biomedical field in the future (n=415, 62.32%); and 5) Preprinting allows for more efficient scientific dissemination (n=400, 60.06%). In terms of whether respondents agreed or disagreed with the statement “Preprinting may encourage other researchers to steal project ideas (i.e., scooping), less than half of (n=304, 45.66%) respondents agreed, 143 (21.47%) respondents remained neutral, and 219 (32.89%) respondents disagreed. On the other hand, 284 respondents (42.71%) did not agree that preprinting would ultimately lead to higher-quality research being published, while 224 (33.68%) and 157 (23.60%) respondents chose neutral and agreement options, respectively.\n\nWe then asked the extent to which respondents agreed with the following motivations for publishing a preprint (Figure 4). Of the 666 respondents who answered, over half had positive attitudes toward the following incentives and consequences: 1) Preprinting increases authors’ visibility and allows for networking (n=489, 73.43%); 2) Preprinting allows for early/more feedback on their manuscript submission (n=470, 70.58%); 3) Preprinting allows authors to share studies that have been rigorously conducted but present negative/perceived low-impact results (i.e., lower likelihood of publication in a peer reviewed journal) (n=437, 65.70%); 4) Preprinting makes my research visible to all if it is published in a paywall journal (n=415, 62.89%); and 5) Preprinting increases the likelihood of authors receiving more views and citations on their published article (n=365, 55.14%). In addition, slightly less than half of respondents (n=323, 48.57%) agreed that preprinting allows authors to prevent duplication of efforts, while 193 (29.02%) disagreed, and 149 (22.42%) remained neutral. In terms of if respondents agreed or disagreed with the statement “Preprints aid researchers’ careers with respect to hiring, promotion, and tenure”, respondents’ opinions were more evenly split, with 205 (30.91%) respondents agreeing, 218 (32.88%) respondents remaining neutral, and 240 (36.19%) respondents disagreeing.\n\nIn addition, we asked participants for their opinions on making preprinting mandatory during the research process. Of the 665 respondents who expressed opinions, over half (n=363, 54.58%) were leaning toward disagreeing with the statement. Only approximately a quarter (n=163, 24.52%) of the respondents had positive opinions regarding this statement.\n\nWe then asked an open-ended question to allow respondents to freely express other factors that motivated or dissuaded them from preprinting (Table 3). The 197 responses could be primarily split into positive and negative factors. The most prevalent positive factor that motivated preprinting “Preprints allow rapid dissemination”. This was followed by “Preprints show research efforts,” in which preprinting allowed authors to show their research to other parties, such as other researchers, funding agencies, and universities, without the use of a publication in a journal. Lastly, the final positive factor commonly mentioned was “Preprints are open-access items”.\n\nOn the other hand, the open-ended questions showed that many negative factors discouraged respondents from preprinting. The most frequent, with approximately a third of responses, was “Peer review is bypassed,” as many responses state that peer review must be carried out to show credibility and quality of research before publishing. In addition, many responses believed that “Preprinting is not needed,” since preprinting does not provide any benefits to the individual’s career and there were no issues with the current publishing system. Another negative factor was “Preprint might release misinformation,” followed by “Preprints are poor-quality research.” Next, many responses stated that the journal policy prevented preprinting”, since journal policy rejected or was unclear about the preprints. “Scooping” was also mentioned frequently, along with “Preprinting requires additional resources,” where respondents felt that preprinting needed extra time, effort, and money that is unnecessary for the overall publication of their work. Additionally, many respondents were “Unfamiliar with preprints” which discouraged them from preprinting. Lastly, “Multiple versions of the same paper” was another negative factor, where having a preprint and a journal published version of the same paper results in the release of unedited, possibly incorrect, work and causes confusion when referencing.\n\n\nDiscussion\n\nThe objective of this study was to explore biomedical researchers’ attitudes toward preprints to determine what factors influence their opinions about publishing and viewing preprints. We found that the most impactful preventative factors against preprinting were the fear of disseminating misinformation, lack of peer review, and unsupportive journal policies. While hiring, promotion, and tenure do not encourage preprinting, respondents believed that preprints are beneficial in increasing visibility and recognition, being openly accessible, providing rapid feedback, and publishing negative data.\n\nFuture work may focus on determining how to improve researchers’ attitudes toward preprinting and how other stakeholders can implement and modify their preprint policies in the future. To the best of our knowledge, this cross-sectional survey is the first to focus exclusively on biomedical researchers to explore their attitudes toward preprinting. The results of this approach are essential for gaining a clearer understanding of the perspectives that biomedical researchers have on preprints, which can potentially impact how other researchers, institutions, and publishing houses implement preprint policies in the future to improve preprinting in biomedical researchers.\n\nIn terms of the benefits and consequences of preprints, the three statements that respondents most agreed with were: 1) Preprints support open science practices, 2) Preprints should not be cited because they may contain results that lack credibility because they have not yet undergone peer review, and 3) Preprints can be used as a weapon for the dissemination of misinformation. These results align with the preliminary work done by Funk et al. (https://asapbio.org/), who found that the most concerning issues with preprints from the perspective of respondents were premature media coverage and public sharing of information prior to peer review, while respondents believed that the top benefit of preprints is open access.\n\nOn the other hand, the top three most impactful factors among respondents with respect to deciding to publish a preprint included 1) increasing author visibility and networking opportunities, 2) allowing for early and more feedback on manuscripts, and 3) publishing of negative or perceived low-impact results. The findings by Funk et al. somewhat align with our results, as they found that only over half of the respondents found early feedback as “very beneficial” and were only seen as less impactful in comparison to open access and speed of dissemination. However, publishing negative or perceived low-impact results was the second least impactful factor, only being seen as “very beneficial” by approximately one-third of the respondents. This variation may be due to more awareness of the bias of journals toward positive results, and why this is an issue for the scientific community. Oftentimes, authors aim to only publish positive “groundbreaking” results, and journals often reject papers with negative or non-significant results to increase readers, citations, and submissions.14,15 However, negative and non-significant results are vital to the scientific process as they allow for collective self-correcting progress and ensure that resources are not wasted on the replication of failed research.15,16 A survey by Echevarría et al.17 showed that the majority of authors believe this information should be shared, although only a handful have tried to publish negative results. Preprints may be an appropriate alternative for publishing negative data as they can quickly share this information without a long peer review process, there is no chance of the manuscript being rejected, and there are no concerns with journal metrics. Future work should focus on gaining a better understanding of researchers’ attitudes toward publishing negative results and preprint practices to ensure that negative results are appropriately disseminated within the scientific community.\n\nOne hesitation toward the use of preprints revolves around the fact that preprints have not undergone peer review; therefore, the scientific content has not been validated before being released to the public. This is seen in our findings, in which almost two-thirds of our respondents believe that preprints should not be cited because the results may lack credibility since there was no peer review. Moreover, over two-thirds of our respondents had viewed or downloaded a preprint, but only a quarter had ever cited it, implying distrust in preprint content. Additionally, peer review being bypassed was the most frequent factor that negatively impacted respondents’ motivations to preprint, as seen in the open-ended question, alongside the fear that preprints will disseminate misinformation and poor-quality research. Thus, we consistently observed that peer review is regarded as highly important and necessary for publishing research by respondents. Respondents’ hesitation toward preprints due to lack of peer review and fear of misinformation indicated a lack of knowledge about the evidence regarding the quality of the published literature and the effectiveness of peer review. Work conducted by Zeraatkar et al.18 has shown that there was no evidence that preprints provided results that were inconsistent with peer reviewed publications, specifically seen with COVID-19 treatments. MEDLINE is also currently indexing preprints, supporting research that has been posted to eligible preprint servers for easy discoverability and preservation (https://www.ncbi.nlm.nih.gov/). In addition, it is important to note that peer review is not always effective because of inconsistency and bias, as many peer reviewers have not had standard training, and many training opportunities and courses are not openly accessible online, inhibiting researchers from completing training on peer review.18–22 Thus, this blind belief in peer review may negatively impact researchers’ opinions toward preprints.\n\nInterestingly, despite many respondents distrusting preprints due to a lack of peer review, many were divided on whether peer review should become part of the preprint process. This may be because preprints allow for the rapid dissemination of research as there is a delay from journal submission to publication when undergoing peer review.1,5 If peer reviews were to be incorporated into preprinting in the same way as it was done for journals, then the work of peer reviewers would increase and the delay would become much longer. Thus, one suggestion may be to modify preprint servers in such a way that they improve the credibility of preprints, as suggested by Soderberg et al.5 The current preprint feedback system allows for public feedback and discussion, which may aid in credibility or results. However, authors often fear unfair criticism from competitors, harm to their reputation, or softened criticism due to the public nature of feedback.7 Fortunately, the FAST principles can alleviate these issues.6 From our findings, the majority of respondents had not peer reviewed a preprint before, and of those that had, most were not familiar with the FAST principles. Therefore, efforts must be made to educate researchers on these principles to promote feedback on preprints. Future work may aim to better understand researchers’ opinions on peer reviewing preprints and potentially provide other novel solutions such that the benefits of peer review can be implemented in the preprinting process without the current fears of preprint feedback.\n\nJournal policy is the second most impactful factor in the decision of authors to post a preprint and was frequently mentioned in the open-ended question. In addition, most respondents were unfamiliar with the journal’s preprint policy. Nowadays, most, but not all, life science journals accept preprinted manuscripts for submission, and some journals either do not have a preprint policy or have contradicting statements.3 Biomedical journals should create clear and concise preprint policies that allow researchers to understand whether they can publish preprints before or during submission to a journal. In addition, our data showed that most researchers do not know of resources on preprint policies, such as Sherpa Romeo and Transpose Publishing, which gather journal policies on open access and preprinting. In the future, it would be best to educate researchers on these types of resources to address the concerns that preprints negatively impact the chances of publishing in a peer reviewed journal.\n\nThe respondents did not have strong opinions on whether preprints aid researchers’ careers with respect to hiring, promotion, and tenure. In addition, our findings showed that universities and research institutes had the least impact on one’s decision to publish a preprint, and the majority of our respondents’ employers neither prohibited nor required the posting of preprints. This may be because few academic institutions/universities consider preprints when hiring and for promotion (https://asapbio.org/). Therefore, hiring, promotion, and tenure policies should be modified, as current methods rely heavily on quantitative metrics, which have been recognized as a flawed system.23 Preprints may prevent the hiring committee’s bias toward or against a journal due to a journal’s impact factor or reputation24 (https://sfdora.org/). The inclusion of preprints in hiring, promotion, and tenure policies may improve biomedical researchers’ attitudes toward preprinting.\n\nBy implementing a cross-sectional survey for this project, we took a snapshot of the population of interest without having to follow them over time. This study’s findings are arguably highly generalizable across biomedical researchers because we randomly surveyed a large sample of biomedical researchers with varying opinions regarding preprint postings. A limitation of our study design was that it was written in English, so researchers without working knowledge of English could not take the survey. In addition, as the present study was based on an English-speaking international sample, it does not consider the impact of national policies on attitudes and opinions toward preprinting. Another limitation of our sampling strategy is that the list of email addresses used potentially included inactive or invalid addresses, which may have been a result of changing professions, retiring, or passing away. Furthermore, we did not consider autoreplies. Therefore, the response rate is underestimated. Our questionnaire was built on self-declared attitudes and preprint practices, which may not accurately capture independently confirmed practices. Inherent to the cross-sectional survey design, the final limitations also include a low response rate, recall bias, in which participants do not correctly remember past events, and non-response bias, in which participants did not want to or could not complete a survey question. In addition, responses mostly reflected the opinions of senior academics, we there were far less participants who were early career researchers, as a result of our sampling strategy.\n\n\nConclusions\n\nIn this study, we surveyed biomedical researchers about their knowledge, experiences, and attitudes toward preprinting. We found that biomedical researchers were familiar with the concept of preprints but lacked experience in working with preprints. The various attitudes and opinions of biomedical researchers provide valuable contributions to the field of publication science and suggests that a number of changes are warranted in the scientific community. To our knowledge, this is the first study to examine the attitudes and opinions of preprints in a discipline-specific manner. Therefore, this study can be used as a model for other academic researchers from alternative disciplines who may be interested in preprinting. Additionally, it would be of value to determine attitudes and opinions in other disciplines to find methods to improve preprinting and researchers’ attitudes toward it. By identifying the attitudes of biomedical researchers towards preprinting, this study’s findings can inform the provision of suggestions to relevant stakeholders for the implemention and improvement of preprinting.\n\n\nConsent\n\nWritten informed consent for publication of the participants’ details was obtained from the participants.",
"appendix": "Data availability\n\nOpen Science Framework: Underlying data for ‘An international, cross-sectional survey of preprint attitudes among biomedical researchers’, https://doi.org/10.17605/OSF.IO/QA9GN. 12\n\nThis project contains the following underlying data:\n\n• Preprints Survey Raw Data_Sep1723.xlsx\n\n• Current Career Stage_Sep1723.docx\n\n• Employment Sector_Sep1723.docx\n\n• Gender_Sep1723.docx\n\n• Participants’ Research Area_Sep1723.docx\n\nOpen Science Framework: Extended data for ‘An international, cross-sectional survey of preprint attitudes among biomedical researchers’, https://doi.org/10.17605/OSF.IO/QA9GN. 12\n\nThis project contains the following extended data:\n\n• Preprints Survey Protocol_Oct0322.pdf\n\n• Preprints Survey_Coding and Themes_Sep1723JYN.xlsx\n\n• Supplementary File 1: Search strategy\n\n• Supplementary File 2: Survey\n\nOpen Science Framework: CHERRIES checklist for ‘An international, cross-sectional survey of preprint attitudes among biomedical researchers’, https://doi.org/10.17605/OSF.IO/QA9GN. 12\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nFraser N, Mayr P, Peters I: Motivations, concerns and selection biases when posting preprints: A survey of bioRxiv authors.2021 Sept 7. 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Publisher Full Text\n\nEbrahimzadeh S, Cobey KD, Page M, et al.: A Cross-sectional Survey on Biomedical Researchers Perceptions of Reproducibility: a Study Protocol.2022. Publisher Full Text\n\nNg JY, Chow V, Santoro LJ, et al.: A survey of preprint practices among biomedical researchers. [Dataset]. 2023. Publisher Full Text\n\nEysenbach G: Improving the quality of web surveys: The checklist for reporting results of internet E-surveys (cherries). J. Med. Internet Res. 2004; 6(3). PubMed Abstract | Publisher Full Text | Free Full Text\n\nFanelli D: Do pressures to publish increase scientists’ bias? an empirical support from US states data. PLoS One. 2010 Apr 21; 5(4): e10271. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFanelli D: Negative results are disappearing from most disciplines and countries. Scientometrics. 2011 Sept 11; 90(3): 891–904. Publisher Full Text\n\nNimpf S, Keays DA: Why (and how) we should publish negative data. EMBO Rep. 2019 Dec 20; 21(1): e49775. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEchevarría L, Malerba A, Arechavala-Gomeza V: Researcher’s perceptions on publishing “negative” results and open access. Nucleic Acid Ther. 2021 Jun 1; 31(3): 185–189. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZeraatkar D, Pitre T, Leung G, et al.: Consistency of covid-19 trial preprints with published reports and impact for decision making: Retrospective review. BMJ Med. 2022; 1(1): e000309. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmith R: Peer Review: A flawed process at the heart of Science and journals. J. R. Soc. Med. 2006 Apr 1; 99(4): 178–182. Publisher Full Text\n\nPublons’ Global State of Peer Review 2018. Publons.2018. Publisher Full Text\n\nWillis JV, Cobey KD, Ramos J, et al.: Limited online training opportunities exist for scholarly peer reviewers. J. Clin. Epidemiol. 2023 Jul 6; 161: 65–73. PubMed Abstract | Publisher Full Text\n\nWillis JV, Ramos J, Cobey KD, et al.: Knowledge and motivations of training in peer review: An International Cross-sectional survey. PLoS One. 2023 Jul 12; 18(7): e0287660. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoher D, Naudet F, Cristea IA, et al.: Assessing scientists for hiring, promotion, and tenure. PLoS Biol. 2018 Mar 29; 16(3): e2004089. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcKiernan EC, Schimanski LA, Muñoz Nieves C, et al.: Use of the journal impact factor in Academic Review, promotion, and tenure evaluations. elife. 2019 Jul 31; 8. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "280674",
"date": "08 Jun 2024",
"name": "Artemis Chaleplioglou",
"expertise": [
"Reviewer Expertise Library and information science (LIS)",
"Bibliometrics",
"Health information"
],
"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 pre-registered cross-sectional online survey study (https://doi.org/10.17605/OSF.IO/QA9GN) aims to assess biomedical researchers' attitudes towards preprinting as well as the factors, incentives and motivations that affect their opinions or decisions about preprints. Factors such as scientific journal policies, co-author consensus, lead author consensus, funding agency policies, and employers or host research institute perspectives were considered. The scientific questions posed by the authors are important in understanding the behavior of biomedical scientists in authoring, searching, accessing, reading, reviewing, citing, accepting or rejecting the evidence presented in preprints. The survey includes demographics, scientific publishing, preprint and peer review related questions. The collected survey data suggested a significant degree of familiarity with the preprint concept in biomedical scientific communication, viewing or downloading a preprint. However, the participants exhibited limited previous preprint contributions and lack of willingness to contribute or cite one in the future. Also, only a handful of the responders have participated in peer reviewing of preprints. The authors followed the sampling framework that was used by Ebrahimzadeh et al (https://doi.org/10.17605/OSF.IO/8NKZF) in a similar contacted cross-sectional survey of biomedical researchers’ perceptions of reproducibility. Briefly, in the first step, the authors used the tens of thousands of journals of MEDLINE database to pick at random 400 out of them (approximately 1.3%). Then, in the second step the authors extracted the names and emails of paper contributors in these randomly selected journals between 2021/01/01 and 2022/08/01. Tens of thousands of authors were invited to participate and complete the survey. By default, the sampling framework design targeted predominantly to lead author investigators. This is because it is common for scientific journals to include only the correspondent author email addresses. Therefore, it is not surprising that most participants are academic faculty members (almost 80%). This is a strong point of the survey because the lead authors take the final decisions over the publishing or preprinting options for a paper. This finding was outlined in the report as the predominant limiting factor in preprint contributions. The fear of scooping may be among the factors and attitudes that strongly affect preprinting. There are investigators that because of this are hesitant over conference proceeding contributions as well. The predominant concern is about the first step of the random selection of journals from MEDLINE database (ncbijournals[All Fields]). Only a fraction of 12.5% of this list represents PubMed indexed journals (currentlyindexed[All Fields]). On top, in MEDLINE database catalog in addition to scientific journals there are other types of serial publications as well such as conference proceedings or workshops. It is not clear whether an additional screening was performed to ensure that only journals were included in the study. The odds of randomly picking a PubMed, Web of Science or SCImago indexed journal from this catalog appear to be pretty low. The odds may be even lower to pick high impact journals from the list. For this reason, it will add significantly if the authors provide the list of the journals or serial publications used in the survey as a supplement. This is also important because some journals actively support the submission to preprint servers whilst they implement preprint scooping-protection policies (https://doi.org/10.1371/journal.pbio.3002502). The attitudes of the responders over preprints could be affected by the journals they published. Besides, the presentation of the randomly selected journals is important to ensure reproducibility. It could be postulated that clinical and pre-clinical researchers dominate the sample over basic research biomedical investigators because of the MEDLINE database content and the selection process. The Strengths and limitations section could be updated to include these limitations. In future studies it would be interesting to assess the attitudes of biomedical researchers preprint contributors over preprinting, open science, publishing, and traditional journal peer reviewing. A very interesting finding of this report is that despite the attitudes over preprinting almost 10% of the participants in the survey suggested that the peer review is bypassed.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12641",
"date": "04 Nov 2024",
"name": "Jeremy Ng",
"role": "Author Response",
"response": "Reviewer 1 Comment: This pre-registered cross-sectional online survey study (https://doi.org/10.17605/OSF.IO/QA9GN) aims to assess biomedical researchers' attitudes towards preprinting as well as the factors, incentives and motivations that affect their opinions or decisions about preprints. Factors such as scientific journal policies, co-author consensus, lead author consensus, funding agency policies, and employers or host research institute perspectives were considered. The scientific questions posed by the authors are important in understanding the behavior of biomedical scientists in authoring, searching, accessing, reading, reviewing, citing, accepting or rejecting the evidence presented in preprints. The survey includes demographics, scientific publishing, preprint and peer review related questions. The collected survey data suggested a significant degree of familiarity with the preprint concept in biomedical scientific communication, viewing or downloading a preprint. However, the participants exhibited limited previous preprint contributions and lack of willingness to contribute or cite one in the future. Also, only a handful of the responders have participated in peer reviewing of preprints. The authors followed the sampling framework that was used by Ebrahimzadeh et al(https://doi.org/10.17605/OSF.IO/8NKZF) in a similar contacted cross-sectional survey of biomedical researchers’ perceptions of reproducibility. Briefly, in the first step, the authors used the tens of thousands of journals of MEDLINE database to pick at random 400 out of them (approximately 1.3%). Then, in the second step the authors extracted the names and emails of paper contributors in these randomly selected journals between 2021/01/01 and 2022/08/01. Tens of thousands of authors were invited to participate and complete the survey. By default, the sampling framework design targeted predominantly to lead author investigators. This is because it is common for scientific journals to include only the correspondent author email addresses. Therefore, it is not surprising that most participants are academic faculty members (almost 80%). This is a strong point of the survey because the lead authors take the final decisions over the publishing or preprinting options for a paper. This finding was outlined in the report as the predominant limiting factor in preprint contributions. The fear of scooping may be among the factors and attitudes that strongly affect preprinting. There are investigators that because of this are hesitant over conference proceeding contributions as well. Response: We kindly thank you for providing your feedback on our manuscript. Comment: The predominant concern is about the first step of the random selection of journals from MEDLINE database (ncbijournals[All Fields]). Only a fraction of 12.5% of this list represents PubMed indexed journals (currentlyindexed[All Fields]). On top, in MEDLINE database catalog in addition to scientific journals there are other types of serial publications as well such as conference proceedings or workshops. It is not clear whether an additional screening was performed to ensure that only journals were included in the study. The odds of randomly picking a PubMed, Web of Science or SCImago indexed journal from this catalog appear to be pretty low. The odds may be even lower to pick high impact journals from the list. For this reason, it will add significantly if the authors provide the list of the journals or serial publications used in the survey as a supplement. This is also important because some journals actively support the submission to preprint servers whilst they implement preprint scooping-protection policies (https://doi.org/10.1371/journal.pbio.3002502). The attitudes of the responders over preprints could be affected by the journals they published. Besides, the presentation of the randomly selected journals is important to ensure reproducibility. Response: We used specific filters from the NLM catalog to ensure that only journal entries were shown. This has been addressed in the Methods of the manuscript. A list of the 400 journals used were included in the Extended Data. Comment: It could be postulated that clinical and pre-clinical researchers dominate the sample over basic research biomedical investigators because of the MEDLINE database content and the selection process. The Strengths and limitations section could be updated to include these limitations. Response: The reviewer brings up a valid point, which we have now written about in the Strength and Limitations of the manuscript. Comment: In future studies it would be interesting to assess the attitudes of biomedical researchers preprint contributors over preprinting, open science, publishing, and traditional journal peer reviewing. A very interesting finding of this report is that despite the attitudes over preprinting almost 10% of the participants in the survey suggested that the peer review is bypassed. Response: We agree with this suggestion and have briefly described this within the Discussion of the manuscript."
}
]
},
{
"id": "291988",
"date": "13 Jul 2024",
"name": "Kimberly Powell",
"expertise": [
"Reviewer Expertise Librarianship",
"Scholarly Communications",
"Bibliometrics",
"Research Impact",
"Open Access Policies",
"Predatory Publishing"
],
"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 offers a broad survey of biomedical authors, identified by 12month sampling of MEDLINE publications, to summarize the awareness, attitudes, and use of preprints. The abstract claims findings can be used to assist stakeholders to more effectively implement preprinting behaviors, and an awareness of author landscape of attitudes and motivations is certainly required to inform more effective policies for support. However, the stated goal of the survey is clearly to increase preprinting and create a more favorable view of preprints rather than taking a more neutral perspective. While I do believe the survey to be well designed and executed, I do have some reservations about the presented framing of the study, as well as lack of formal citations supporting some areas of discussion. A significant portion of the discussion is dedicated to de-valuing peer-review which is not based in study data but rather the authors response to respondents perceived lack of awareness of concerns around the modern peer-review process. This particular framing would be better supported by introducing it in the introductory paragraphs and presenting preprints as a reasonable alternative so readers could be better prepared for this line of reasoning. Specific comments and suggestions are enumerated below:\nMethods section open science statement offers a reference link for the OSF datafiles. Please also provide a reference link for the MedRxiv preprint. The first paragraph of the introduction includes two parenthetical references to https://asapbio.org. With another instance in the third paragraph of the discussion. Additional context clues this reference in the discussion indicate that the proper citation should be made the ASAPbio blog page from 2020-07-27 available here: https://asapbio.org/biopreprints2020-survey-initial-results. All ASAPbio citations should be updated to formally appear in the reference list with their direct blog links. The references in the introduction do not offer enough information to track down the intended citations but should be updated to the appropriate reference information as well. A fourth orphaned ASAPbio reference is also made in the second paragraph of the “External Factors…” section of the discussion. Final sentence of the Methods paragraph on Participant Recruitment predicts a 10% response rate. Since this is remarkably different the that 3.2% response rate, I wonder if the authors could provide any justification or rationale for the 10% prediction. Was this estimate based on similar author-response studies? Length/survey presentation/etc. Citations supporting this estimate would be appreciated for further research and study design. I was confused by the inclusion of ResearchGate as a common preprint server to view/download preprints as presented in the Discussion section on Viewing/downloading preprints. Did 20.53% of respondents think downloading articles from ResearchGate equated to engaging with preprints? What about those cases where ResearchGate allows for downloading of the final publisher version? Can additional context around this survey question be provided to indicate how respondents thought ResearchGate related to preprints? I think to present it primarily as preprint server is a very concerning misunderstanding of the ResearchGate platform. I was startled by the data presented in Table 2 and I do not think the introduction appropriately framed the issue of mandating peer review in the preprinting process as something that would even be asked in such a survey. When the first sentence of the manuscript offers a definition of preprint as something “which has not yet undergone formal peer review” the survey question of mandating peer-review become incongruous with the definition of what is being studied. Similarly, if authors wish to present trust in peer-review as a key takeaway of the survey results, concerns around peer-review, and the role of preprints as one possible alternative, would be better introduced in the introduction of the manuscript. Table 3 respondent column should be presented as a percentage of the total responses for that question, as provided in all other figures. The first paragraph of the discussion presents three main findings of the study that fear of misinformation, lack of peer review, and unsupportive journal policies were the most impactful preventative factors against preprinting. I am not convinced this is an appropriate representation of the data. While the first two points may indeed be primary concerns, I think unsupportive journal policies is an overstatement of the presented data which instead highlights respondents lack of awareness around journal policies and policy tools. While Figure 1 does show Journal Policy to be a more significant influence on choose to preprint than other factors, Figure 2 highlights that over 50% of authors aren’t familiar with journal policies at all or don’t remember the journal policies towards preprints for their last submissions. These data seem to support a lack of awareness on the part of the author, and not unsupportive journals. In fact, only 5% of authors are shown to be aware that their last journal for submission prohibited preprinting. The lack of author awareness is further discussed in the seventh paragraph of the discussion but the summarizing of this as “unsupportive journal policies” needs further justification. Relatedly, please add reference(s) to the claims that “most, but not all, life science journals accept preprinted manuscripts for submission” as this should be a key point of context.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12642",
"date": "04 Nov 2024",
"name": "Jeremy Ng",
"role": "Author Response",
"response": "This study offers a broad survey of biomedical authors, identified by 12month sampling of MEDLINE publications, to summarize the awareness, attitudes, and use of preprints. The abstract claims findings can be used to assist stakeholders to more effectively implement preprinting behaviors, and an awareness of author landscape of attitudes and motivations is certainly required to inform more effective policies for support. However, the stated goal of the survey is clearly to increase preprinting and create a more favorable view of preprints rather than taking a more neutral perspective. We kindly thank the reviewer for providing their feedback on our manuscript. While I do believe the survey to be well designed and executed, I do have some reservations about the presented framing of the study, as well as lack of formal citations supporting some areas of discussion. A significant portion of the discussion is dedicated to de-valuing peer-review which is not based in study data but rather the authors response to respondents perceived lack of awareness of concerns around the modern peer-review process. This particular framing would be better supported by introducing it in the introductory paragraphs and presenting preprints as a reasonable alternative so readers could be better prepared for this line of reasoning. We have made changes to the Background of the manuscript to reflect these suggestions. Specific comments and suggestions are enumerated below: Methods section open science statement offers a reference link for the OSF datafiles. Please also provide a reference link for the MedRxiv preprint. We have added a reference for the MedRxiv preprint. The first paragraph of the introduction includes two parenthetical references to https://asapbio.org. With another instance in the third paragraph of the discussion. Additional context clues this reference in the discussion indicate that the proper citation should be made the ASAPbio blog page from 2020-07-27 available here: https://asapbio.org/biopreprints2020-survey-initial-results. All ASAPbio citations should be updated to formally appear in the reference list with their direct blog links. The references in the introduction do not offer enough information to track down the intended citations but should be updated to the appropriate reference information as well. A fourth orphaned ASAPbio reference is also made in the second paragraph of the “External Factors…” section of the discussion. Following the F1000Research Guidelines for Research articles which states that, “Web links should be included as hyperlinks within the main body of the article, and not as references”, citations and references have been updated. We kindly thank you for your feedback. Final sentence of the Methods paragraph on Participant Recruitment predicts a 10% response rate. Since this is remarkably different the that 3.2% response rate, I wonder if the authors could provide any justification or rationale for the 10% prediction. Was this estimate based on similar author-response studies? Length/survey presentation/etc. Citations supporting this estimate would be appreciated for further research and study design. We conducted a survey involving individuals who were unfamiliar to us, anticipating a low response rate due to the challenges associated with recruiting participants for cross-sectional online surveys. In addition, we cannot tell how many authors had authors moved institutions, were on vacation, were ill, and passed away and thus, were unable to respond. We did try to increase the response rate by sending personalized reminders and keeping the survey completable in under 20 minutes long, as suggested by Menon and Muraleedharan (doi: 10.1136/gpsych-2020-100264). I was confused by the inclusion of ResearchGate as a common preprint server to view/download preprints as presented in the Discussion section on Viewing/downloading preprints. Did 20.53% of respondents think downloading articles from ResearchGate equated to engaging with preprints? What about those cases where ResearchGate allows for downloading of the final publisher version? Can additional context around this survey question be provided to indicate how respondents thought ResearchGate related to preprints? I think to present it primarily as preprint server is a very concerning misunderstanding of the ResearchGate platform. We had listed ResearchGate as it is acknowledged as a preprint server on the ASAPBio preprint server directory (https://asapbio.org/preprint-servers). We did not collect any specific information regarding respondents’ opinions of ResearchGate and whether this equated to engaging with preprinting. I was startled by the data presented in Table 2 and I do not think the introduction appropriately framed the issue of mandating peer review in the preprinting process as something that would even be asked in such a survey. When the first sentence of the manuscript offers a definition of preprint as something “which has not yet undergone formal peer review” the survey question of mandating peer-review become incongruous with the definition of what is being studied. Similarly, if authors wish to present trust in peer-review as a key takeaway of the survey results, concerns around peer-review, and the role of preprints as one possible alternative, would be better introduced in the introduction of the manuscript. We have described the issues around peer review and preprints as an alternative in the Background of the manuscript. Table 3 respondent column should be presented as a percentage of the total responses for that question, as provided in all other figures. We have updated Table 3 to include the percentage as suggested. The first paragraph of the discussion presents three main findings of the study that fear of misinformation, lack of peer review, and unsupportive journal policies were the most impactful preventative factors against preprinting. I am not convinced this is an appropriate representation of the data. While the first two points may indeed be primary concerns, I think unsupportive journal policies is an overstatement of the presented data which instead highlights respondents lack of awareness around journal policies and policy tools. While Figure 1 does show Journal Policy to be a more significant influence on choose to preprint than other factors, Figure 2 highlights that over 50% of authors aren’t familiar with journal policies at all or don’t remember the journal policies towards preprints for their last submissions. These data seem to support a lack of awareness on the part of the author, and not unsupportive journals. In fact, only 5% of authors are shown to be aware that their last journal for submission prohibited preprinting. The lack of author awareness is further discussed in the seventh paragraph of the discussion but the summarizing of this as “unsupportive journal policies” needs further justification. Relatedly, please add reference(s) to the claims that “most, but not all, life science journals accept preprinted manuscripts for submission” as this should be a key point of context. We have used the reviewer’s suggestions to put more emphasis of the “unfamiliarity of journal’s preprint policies” over “unsupportive journal policies”. We should note that there was a reference to the claim ““most, but not all, life science journals accept preprinted manuscripts for submission”."
}
]
}
] | 1
|
https://f1000research.com/articles/13-6
|
https://f1000research.com/articles/13-237/v1
|
28 Mar 24
|
{
"type": "Systematic Review",
"title": "Explicating collegiality and change management in neoliberalism during the dynamics of higher education institutions",
"authors": [
"Makna Ani Marlia",
"Rahmi Fahmy",
"Hendra Lukito",
"Donard Games",
"Makna Ani Marlia",
"Hendra Lukito",
"Donard Games"
],
"abstract": "Background This paper discusses the lack of references that comprehensively describe the changes in universities owing to the ideology of neoliberalism. This research also discusses how a university maintains its function and identity when the great wave of neoliberalism massively erodes collegiality as the original philosophy of the university through a case study of the neoliberalism ideology on higher education. This study also provides a comprehensive framework for higher education management and governance changes.\n\nMethods We selected all retrieved sources based on the keywords and analyzed all the documents we obtained. This study obtained data from Scopus retrieved on October 27, 2023, using the following keywords: (TITLE-ABS-KEY (\"collegiality\") OR TITLE-ABS-KEY (\"change management\") OR TITLE-ABS-KEY (\"neolibelism\")) AND TITLE-ABS-KEY (\"higher education\"). This study utilized bibliometric analysis to ensure a structured review of the literature on collegiality, change management, and neoliberalism in higher education.\n\nResults The findings show that organizational management, leadership, education, technology, curriculum, innovation, organizational change, decision-making, and human beings are significant trajectories of neoliberalism in higher education.\n\nConclusions This study offers other constructs for accelerating leadership success in higher education. This relates to how change leadership can navigate changes resulting from neoliberal ideology.",
"keywords": [
"change management",
"collegiality",
"neoliberalism",
"NPM",
"managerialism",
"higher education"
],
"content": "Introduction\n\nGlobalization and neoliberalism in higher education create different pressures and demands for reform. Adopting neoliberal behavior and ideology focuses on the importance of market dynamics in social exchange throughout university activities. Higher education has shaped changes in organizational practices, processes, and culture (Ajayan & Balasubramanian, 2020; Croucher & Lacy, 2022; Gaus, Basri, Thamrin, & Ritonga, 2020; Hamlin & Patel, 2017). Traditionally, before the 1980s, universities were established for public and collegial management aimed at public welfare, which was considered the best way to manage all the unique attributes of universities. Before neoliberalism, universities were influenced by the ideology of managerialism, which radically uprooted this idea (Fleming, 2020). The adoption of neoliberal ideology in the form of New Public Management (NPM) or New Managerialism has shifted the traditional approach to what is said to be a corporate or business approach (Ajayan & Balasubramanian, 2020; Fleming, 2020; Martin-Sardesai, Guthrie, Tooley, & Chaplin, 2019).\n\nOsborne and Gaebler (1992) developed the NPM in the context of the United States, which has promoted the principles of business in Higher Education through value for money, quality assurance, monitoring, evaluation, auditing, and accountability (Ajayan & Balasubramanian, 2020; Gaus et al., 2020; Gaus, Tang, & Akil, 2019; Gaus & Hall, 2015). Integrating the concept of corporatization or commercial practices into higher education and academia and using performance-based metrics indicates government control (Gaus & Hall, 2016) and coercion disguised through technological policies (Foucault, 1982). This undermines academic independence and autonomy, resulting in the prioritization of financial interests in public service administration, commonly referred to as a “money culture”.\n\nDespite the corrosive effects of the NPM agenda on higher education and the work of academia, it continues to evolve in higher education worldwide (Christopher, 2012a; Haake, 2009; Hossan, 2015; Middlehurst, 2004; Yokoyama, 2006), including Indonesia (Gaus, 2019b; Gaus et al., 2020, 2019; Gaus & Hall, 2015, 2016). The governments of Malaysia and Thailand strongly believe in the doctrine of neo-liberalism, believing that implementing market concepts and strategies would enhance service delivery and foster good governance in the public sector. (Gaus & Tang, 2023; Taib & Abdullah, 2015). These changes affected each university’s mission, values, and overall operations at different levels of change.\n\nSome researchers have discussed the application of NPM/managerialism in higher education, such as Mok (1999), in his study of higher education sectors in Hong Kong, stating that implementing managerialism has led organizations to adopt a more “customer-oriented” approach and treat consumers. Kalfa and Taksa (2016) found that institutions that follow the practice of managerialism focus on developing robust relationships with stakeholders, such as industries that expect graduates to have the skills to obtain employment. Thus, managerialism requires universities to be more entrepreneurial in terms of having alternative earnings mechanisms (Ajayan & Balasubramanian, 2020). However, Nickson (2014) lamented that colleges may be able to sacrifice academic freedom and collegiality to obtain alternative sources of income. Gaus and Tang (2023) espoused NPM from the application of neoliberal ideology with its economic rationality leading to the corporatization of higher education has preserved the business lexicon, such as individualism, competence, effectiveness, and efficiency, where individual and personal interests take precedence over the interests of society.\n\nThis is in line with Fleming’s (2020) expressed as The Dark Academia, which revealed that the transformation resulting from neoliberal currents had changed universities to become more corporative, more commercial, and universities such as Edu Factory, which produce mass and make students as consumers who need to be satisfied and served, while lecturers become factors of production and isolated from the ideal world. Where the lecturer profession is a lifestyle, not everyone can enter it. Academics are highly trained specialists who have dedicated themselves and time to the grueling study of their chosen discipline. No one in the organization, including the university’s line manager, is more knowledgeable about their teaching and research fields. A simple top-down hierarchy does not work in this setting and becomes a barrier. Unlike manual workers, who have to produce a certain amount that can be quantified, academic work is abstract and cannot be driven by performance incentives like factories, but academics carry out the profession in this sector wholeheartedly.\n\nThe government is closely associated with neoliberalism in its role as a regulatory authority. This ideology seeks to address inefficiencies in the public sector by implementing corporate practice. The aim is to make universities more efficient, productive, customer-oriented, and accountable (Ajayan & Balasubramanian, 2020). The World Bank, UNESCO, and OECD endorse the evolving perspective that education may be treated as a tradable asset with the potential to generate lucrative revenue (Lynch, 2015). Universities worldwide face the challenge of adapting to the growing number of “business-like” Higher Education institutions. This necessitates a shift towards a more entrepreneurial approach, focusing on achieving greater efficiency and improving overall quality (Robertson, 2010). In addition, the rise of managerialism/new Public Management (NPM) in the higher education sector is motivated by the need to showcase academic standards (quality assurance/QA) and research output to secure government and industry funding, predominantly contingent on performance. Additionally, there is a need to enhance an institution’s reputation to attract both local and international students (Ajayan & Balasubramanian, 2020).\n\nVarious phenomena that arise due to the adoption of the ideology of neoliberalism also seem to cause other corrosive effects, especially pressure from various stakeholders in higher education; the primary sources of pressure on universities are students, the government, the business world, and local communities. This has resulted in universities having to seriously examine their management and governance. Carbone et al. (2019) found that higher education that nurtures the value of collegiality tends to be more successful in managing change by maintaining the quality of the education. However, the study involved only one institution of higher education and the findings may not be generalizable to other contexts. On the other hand, Brown and Edmunds (2020) showed that neoliberalism often encourages higher education to sacrifice collegiality for efficiency and competition. This can lead to tension between lecturers and university management, which may affect the quality of the education.\n\nThus, previous governance models based on collegiality may not be fully sustained considering customer pressure regarding business-like expectation responses in dynamic settings (Davies, Hides, & Casey, 2001). The rationale for the review in the context of existing knowledge is to address the gap in understanding how neoliberalism influences collegiality and change management in higher education institutions. Neoliberal ideology has significantly impacted the governance and operation of universities, leading to shifts in power dynamics, decision-making processes, and organizational structures. By examining the existing literature on this topic, the review aims to provide insights into universities’ challenges and opportunities in adapting to neoliberal reforms. This paper discusses the lack of references that comprehensively describe the changes that occur in universities owing to the ideology of neoliberalism. This research also discusses how a university maintains its function and identity when the great wave of neoliberalism massively erodes the collegiality that was the original philosophy of the university, through a case study of the impact of neoliberalism ideology on higher education. This study also provides a comprehensive framework for changes in higher education management and governance.\n\nHow does neoliberalism erode collegiality in higher education?\n\n1. How does the ideology of neoliberalism give a pattern to change in higher education?\n\n2. What kind of management and governance can increase the competitiveness of universities in facing the challenges of the neoliberal environment?\n\nChange is identified as a shift in organizational behavior from one form to another. Change management has been identified as continuously upgrading the supervision, structure, and service to meet customer needs, either internal or external (Akinbode & Shuhumi, 2018; Almanei, Salonitis, & Tsinopoulos, 2018). Organizational change is necessary when organizations are no longer in harmony with their outward setting and existence is vulnerable (Price & Chahal, 2006; Oreg, Vakola, & Armenakis, 2011). However, organizations continually encounter fierce struggles under pressure that require them to adjust their strategies, technologies, and other processes to survive (Almanei et al., 2018). Change is a steady, continuous process, and not just a situation that occurs once (Almanei et al., 2018). Change management is a discipline that provides the transition among individuals, teams, or entire managed organizations to lead and guide the process to the desired state by solving various types of resistance (Almanei et al., 2018).\n\nBased on several theories about change management that have been explained by Lewin’s theory (Lewin, 1947) is the most critical concept of change methods development (Aldulaimi & Abdeldayem, 2020) and is the theoretical basis for modern change models (Vlachopoulos, 2021) which are built from the first three stages of change, unfreezing, which is the process of awareness about the need or need to change. Second, changing/moving is a step action to strengthen driving forces or reduce resistance, and third, refreezing is bringing the organization back to a new equilibrium, better known as a new dynamic equilibrium, and researchers make this theory a grand theory of change management in this study.\n\nUniversities have undergone significant changes in governance and management. This has been well-documented in various studies (Bolden, Petrov, & Gosling, 2009; Clegg & McAuley, 2005; Enders, De Boer, & Leisyte, 2008; Hamlin & Patel, 2017; Smith, 2005; Vuori, 2015). Traditionally, the College is governed by policies that administrative leaders manage. However, changes driven by various stakeholders make today’s universities manage business management (Davies et al., 2001; Gaus et al., 2020; Gaus & Tang, 2023). These changes have led to academic field transformation in universities into business units run by management, focusing on targets such as companies that work under tight budget limits (Fleming, 2020; Waring, 2017). Based on the literature, a comprehensive analysis of the central changes that occur in universities is presented as a concept map of changes in universities as shown in Figure 1.\n\n\nMethods\n\nThis research is quantitative with a systematic approach to literature review using bibliometric analysis, and Biblioshiny software version 4.0 is used to analyze data. Bibliometric analysis is used with the consideration that bibliometrics studies can be used to see trends in a field of study and the productivity of journals/authors and is a combination of mathematical models and statistical models (Gumus, Bellibas, Esen, & Gumus, 2018). This method allows researchers to examine abstracts, keywords, and references to specific field studies to reveal their authors, countries, journals, and institutions and can generate scientific collaboration between researchers worldwide. Despite the increase in bibliometric interest in various academic fields, studies using this method are still interesting to explore further in the field of study of each researcher.\n\nWe selected all retrieved sources based on the keywords and analyzed all the documents we obtained. This study obtained data from Scopus retrieved on October 27, 2023, using the following keywords: (TITLE-ABS-KEY (“collegiality”) OR TITLE-ABS-KEY (“change management”) OR TITLE-ABS-KEY (“neolibelism”)) AND TITLE-ABS-KEY (“higher education”). After that, 416 sources were retrieved in Scopus Database within 1971 to 2023 publication year, then 662 documents were obtained (Marlia et al., 2024). In the primary information as shown in Figure 2 and Table 1, it can be seen that there are 662 documents consists of 198 documents that only have single authors with the number of authors consisting of 1401 authors. Of the 1401 authors, approximately 13.14% were listed as international writers; each author wrote an average of 234 articles.\n\nTable 1 shows that, based on document type, most (446 documents) are articles, and the rest are books, book chapters, conference papers, editorials, notes, and reviews.\n\nWe visually display the results of individual studies and syntheses. Tabular presentation of data from individual studies, including author names, publication years, affiliations, and key findings related to collegiality, change management, and neoliberalism in higher education. Comparative tables to highlight differences or similarities between studies in terms of methodologies, results, and implications. Visualization of keyword networks to show relationships between key concepts such as higher education, change management, collegiality, and neoliberalism. Visual representation of the frequency of words or keywords related to collegiality, change management, and neoliberalism in higher education, with the size of each word indicating its occurrence in the articles. Displaying the top 100 words based on the word cloud found in articles, with the size of each word representing the number of occurrences in the article titles. Visual representation of changes in universities influenced by neoliberalism, based on Lewin’s model (Lewin, 1951). By utilizing these methods for tabulating and visually displaying results, we could present a comprehensive overview of the individual studies and syntheses related to collegiality, change management, and neoliberalism in higher education, facilitating a better understanding of the complex dynamics within this academic domain.\n\nBased on Lewin’s model of change in universities, concept mapping was used to illustrate the transformation processes influenced by neoliberalism in higher education. This method provides a structured framework for understanding the changes occurring in educational organizations and the adoption of new practices. Bibliometric analysis was used to analyze the productivity of authors, journals, and institutions in collegiality, change management, and neoliberalism in higher education. This method helps identify trends, collaborations, and impact within the academic community, providing quantitative insights into research output. We also assessed the quality of individual studies through tools like the PRISMA Checklist (Marlia et al., 2024) or risk of bias assessment can help identify sources of heterogeneity related to study design, methodology, or reporting. By evaluating study quality, we can determine the reliability and validity of results and assess the impact of study quality on overall findings.\n\nWe also involved two fresh professors for data interpretation review. They confirmed our data regarding the Scopus sources and our data interpretation to Biblioshiny output. This study is conducted under ethical approval from Institutional Review Board of Andalas University through ethical approval number: 314/UN16.05/S3.M/2023 on October 2nd, 2023.\n\n\nResults\n\nData analysis with bibliometrics on the trend of research development is presented in this study through several visualizations, such as publication productivity from year to year, from publication in 1971 to 2023, and the results of analysis from the world cloud and Tree Map as a whole present trends in researchers’ discussions about the relationships between collegiality, change management, and neoliberalism in higher education. Researchers in this case also criticize the field of study, which is mostly discussed based on the results of this study. Researchers expect to make significant contributions to the literature. We believe that university leaders must prioritize some issues related to the impact of neoliberal ideology that must be executed with change management in universities without obscuring the initial philosophy or nature of higher education. The following are the results and visualizations of the data analysis using bibliometrics:\n\nAnnual Scientific Production monitors the growth of scientific work production over time. In Figure 3, it can be seen that there was an increase in articles from year to year, with a significant spike occurring from 2017 to 2018. This means that there has been an increase in productivity related to studies that discuss the relationships between collegiality, change management, and neoliberalism in higher education. This productivity is also supported by the high average number of citations per year, which has also increased. This is illustrated in Figure 4.\n\nThis study searched for articles that discussed the relationship between collegiality, change management, and neoliberalism in higher education. Ten sources are the most relevant in Figure 5:\n\n• 15 documents in International Journal of Educational Management\n\n• 11 documents in Journal of Higher Education Policy and Management\n\n• 10 documents in Tertiary Education and Management\n\n• 9 documents in Higher Education\n\n• 9 documents in Innovations in Education and Teaching International\n\n• 9 documents in Journal of Organizational Change Management\n\n• 8 documents in Higher Education Research and Development\n\n• 8 documents in Studies in Higher Education\n\n• 8 documents in Sustainability (Switzerland)\n\n• 7 documents in International Journal of Sustainability in Higher Education\n\nThese sources are also supported by the sources’ local impact according to the H-index (Figure 6), which shows that most relevant sources also have a high H-index. This indicates that journals in higher education dominate collegiality, change management, and neoliberalism. This could mean that those affected more by neoliberalism are nonprofit organizations in the education sector, especially in higher education. The researchers with the most relevance can be seen in Figure 7, namely those with articles published and indexed by Scopus until October 27, 2023. In Figure 7, it can be seen that researchers have relevance related to the relationship between collegiality, change management, and neoliberalism in higher education, which has the most significant relevance, namely Lazano R. and Tapper T. (6 documents), Amaral A., Carvalho T., and Palfreyman D. (5 documents), Angehrn AA and Maxwell K. (4 documents), Ameen K, Awais S., and Blackmore J. (three documents). Most relevant authors are also supported by authors’ production over time (Figure 8), whereas researchers in most relevant authors are also authors’ production over time.\n\nThis section provides information about the affiliations that are most actively publishing scientific articles until 2023 related to the relationship among collegiality, change management, and neoliberalism in higher education according to Figure 9: Monash University (27 documents), University of The Sunshine Coast (18 documents), University of Massachusetts (10 documents), Curtin University (9 documents), Edinburgh Napier University (9 documents), Kennesaw State University (8 documents), University of Oulu (8 documents), Macquarie University (7 documents), National University of Science and Technology (Misis) (7 documents), and Texas A And M University (7 documents). The majority of affiliations related to relationships between collegiality, change management, and neoliberalism in higher education are still dominated by institutions from Australia and America while based on countries whose authors as correspondence are dominated by the United Kingdom, USA, Australia, Malaysia, South Africa, India, Ireland, Portugal, Spain, Sweden, Canada, Germany, Finland, Hong Kong, Indonesia, Netherlands, Pakistan, and the United Arab Emirates (Figure 10).\n\nThe analysis of this author’s affiliation was intended to determine the affiliation that has resulted in many scientific publications on collegiality, change management, and neoliberalism in higher education. The results of this analysis can be used as a reference for future researchers to be used as a reference source for writing advanced articles and collaboration between authors, institutions, journal publication targets, and others.\n\nFigure 11 shows a visualization of the keyword network, color, circle size, and font size. Meanwhile, the thickness of the connecting lines indicates the strength of the relationship between the keywords. The keywords in the image are displayed in the same color and are interconnected. For example, higher education and humans have larger font sizes than others, but have different colors. The line between higher education and change management in human beings shows a close relationship, and researchers have discussed much of the link between these two themes. Figure 10 shows that collegiality, change management, and neoliberalism in higher education are related to humans/humans, organizational innovation, learning, curriculum, organization, and management.\n\nFigures 12 and 13 show the top 100 words based on the word cloud found in all articles on collegiality, change management, and neoliberalism in higher education, obtained as of October 2023. The size of each word represents the number of occurrences in the article’s title. The words shown in Figure 12 are title words trending toward collegiality, change management, and neoliberalism in higher education research that are integrated with other variables. The largest color indicates the most popular research title, whereas the same color indicates a connection. In Figure 12, the World Cloud appears irregular, but the dominant word in scientific publications is placed at the center to make it more visible with the maximum font.\n\nInterconnected keywords are shown in the same color. For example, change management and education have color similarities of different sizes to show a close relationship. From Figure 13, it can also be seen that collegiality, change management, and neoliberalism in higher education are related to organization and management, leadership, curriculum, organizational innovation, organizational change, decision making, and humans. This can be interpreted as the relationship between collegiality, change management, and neoliberalism in higher education is related to leadership, organizational change, management, and humans.\n\nThis is supported by Croucher and Lacy (2022), which states that, in many changes that occur in higher education, a central role played by the holder of positions of authority and the culture of neoliberalism can be implemented through policies set by university leaders through budgeting mechanisms and internal organizational policies related to university governance. This opinion is in line with that of Osseo-Asare, Longbottom, and Murphy (2005), who conducted studies at Australian universities and stated that the ideology of neoliberalism has crossed the space of traditional liberalism. The institutional form of universities with a line management chain model that better maintains the philosophy of collegiality by maintaining a more collegial structure or democracy in a flatter structure has changed to a hierarchical model of authority that emphasizes more hierarchical market forces based on management dictated over the performance of work in the principal-agent chain of command. As the power of neoliberalism and corporate culture intensifies in universities, there are some things that can be seen as directly changing from the human side, such as changing the language used to present and evaluate human behavior and actions (Giroux, 2002).\n\nA shift in college management has occurred in many countries worldwide, with varying positive and negative outcomes (Hamlin & Patel, 2017). Mercer (2009) and Ajayan and Balasubramanian (2020) in their research said that there are four things related to the ideology of neoliberalism in the form of managerialism in universities: 1) increasing internal and external accountability of organizations, where universities have to control the quality of research and teaching based on output, especially graduation rates, publications, and performance indicators; 2) related to the marketization of universities, where universities are becoming more customer-oriented and stimulated academic competition for students, such as getting published in reputable journals; 3) increased emphasis on efficiency where there are restrictions on government and universities funding are required to be able to provide maximum services by reducing service costs; and 4) managerialism promotes entrepreneurial activities by building solid relationships with various stakeholders, collaborating with industry, and finding various alternative short-term and long-term revenue mechanisms to generate revenue. However, this may come at the expense of academic freedom and collegiality (Nickson, 2014). Following some of these assumptions, we can understand that implementing neoliberal ideology in the form of NPM/managerialism has shifted the identity of higher education collegiality towards governance that prioritizes corporatization management.\n\nAn exciting thing that researchers want to criticize here after seeing the results of the bibliometric analysis is the idea of thinking of world scholars. If universities prioritize market forces, what about collegiality in higher education? The theoretical foundation of corporate culture and its role in corporate governance are principally derived from agency theory (Ballantine, Berle, & Means, 1932; Christopher, 2012b). This theory is certainly more in favor of the interests of principals (shareholders), while university management is certainly very different. Therefore, the impact of changes resulting from the implementation of neoliberalism on collegiality in universities must be balanced, lest the values that universities should carry in creating community welfare through the development of science and social justice for the entire community is eroded by the corrosive effect created by market culture that prioritizes business agendas in universities (Croucher & Lacy, 2022; Gaus & Tang, 2023). Do not allow the common goal of establishing universities to create community welfare further away from the original goal. Therefore, each university must realize that this change is inevitable, but must be able to immediately adapt to all the consequences of adapting to the new environment created by the ideology of neoliberalism, which presents some significant challenges for change and increasing the competitiveness of universities.\n\n\nDiscussion\n\nThe forces of globalization have driven the literature review. Changes in higher education have several dimensions. One of the dimensions of globalization is neoliberalism, which implements market forces in higher education. This paradigm shift presents several consequences in higher education, not only on the education side but also on the governance of universities. The results of the bibliometric analysis of the articles used in this study presented a clear and broad view. In this article, we also want to provide a view in accordance with what the researcher captured from a review of research results from previous researchers with a tendency to focus on research in the last five years. Although not in their entirety, the selected articles are featured in this review.\n\nAs discussed earlier, the implementation of the ideology of neoliberalism has been widely studied and has attracted the attention of several researchers (Fleming, 2020; Gaus & Tang, 2023; Gaus et al., 2019). The term neoliberalism is more familiar with the terms corporatization, managerialism/new public management (NPM), and accountability, which explicitly reduce government interference and replace it with the market, assuming that the market is considered the most effective allocator of resources, can encourage innovation and the ability to be entrepreneurial. Universities affected by neoliberalism tend to become more market-oriented, considering technology/digitalization in universities, such as the emergence of many virtual universities, and it is increasingly important for universities to collaborate with strategic alliances and partners to form networking for universities (Dopson et al., 2019). This study summarizes some of the changes in higher education as an influence of adopting neoliberalism, addressing eight central issues related to autonomy, quality assurance (QA), internationalization, market orientation, managerialism, entrepreneurialism, digitalization, collaboration, and leadership. Researchers expect these eight issues to contribute to leaders in higher education making strategic decisions to institute changes in their universities. As input material on the pattern of changes in the orientation of higher education governance, we also complete this research from several points of view, including the differences between educational and business organizations (see Table 2).\n\n\n\n• Traditional. Business leadership is based on the concept that leaders are central to task performance and maintenance of human resource output, emphasizing individual performance equality\n\n• Contemporary. Business leadership is to promote adaptive change by developing a vision of the future and a change strategy\n\n\n\n• Traditional. Academic leadership is characterized by personal academic achievements such as publications in accredited journals, international conferences, and responsibility for academic development\n\n• Contemporary. Academic leadership focuses on leadership qualities, effective and efficient administrative mechanisms, and nuances of interpersonal relationships and empathy\n\nThe acceleration of change in each university will differ depending on how much the organization is ready to respond to challenges and the urgency to adapt to change quickly. The transformation process of change comprehensively considers changes in higher education. We present a framework of thought adapted to Lewin’s (change management and aspects related to various perspectives of change to face the environment of neoliberalism in higher education. The Lewis Change model was used in this study to identify changes occurring in educational organizations and the adoption of what should be re-institutionalized from a change process (Figure 14).\n\nSome countries have focused on developing the concept of autonomy as part of transforming higher education governance into autonomy or self-governance. This is a result of the emergence of the concept of New Public Management (NPM), which began to shift government control into market power ((Nasution, Prasojo, Jannah, & Yumitro, 2020). Influencing forces include various stakeholders and the dynamics of the relationships (agreements) between stakeholders and university governance. Christopher (2012b) details five factors that have influenced the paradigm of higher education governance: 1) Central Government, 2) Local Government, 3) global competition, 4) collegial governance, and 5) internal management.\n\nGranting autonomy to universities is expected to bring about broad changes to the governance and management of institutions. Autonomy refers to “the power and authority of an institution to run its affairs without undue influence or direction from the government” (Taib & Abdullah, 2015). Autonomy can be divided into two types: 1) substantive autonomy and 2) procedural autonomy. Substantive autonomy includes academic and research fields, particularly autonomy related to curriculum design, research policy, degree awarding, and so on. In comparison, procedural autonomy covers non-academic fields that have much to do with financial issues such as borrowing funds, spending budgets, and managing salaries.\n\nGranting autonomy to public universities entails bestowing autonomy in four domains: The first aspect is organizational or institutional autonomy, which entails bestowing universities with the power and authority to establish policies, devise procedures, and make choices to fulfill higher education objectives and purposes through effective governance and accountability frameworks. Financial autonomy refers to the granting of power and authority to Public Universities to create policies, establish procedures, and make decisions regarding financial and revenue management. This is accompanied by a requirement for accountability, transparency, integration, and implementation of effective and efficient management practices (Abdullah & Osman, 2015). Human resource autonomy refers to the level of authority granted to Public Universities to formulate policies and establish processes for organizational development, remuneration, and employee development. This autonomy enables universities to attract, nurture, and retain highly skilled professionals and talented individuals. Furthermore, autonomy in the academic sphere entails endowing state universities with the power and authority to formulate policies in areas such as the establishment and discontinuation of study programs as well as the advancement, execution, and assurance of academic excellence, research and development, innovation, and knowledge dissemination (Taib & Abdullah, 2015). Therefore, granting autonomy helps universities improve their quality through quality assurance.\n\nThe second primary concern revolves around quality assurance in higher education, which refers to the public’s duty to exhibit commendable levels of performance. This matter has garnered significant attention and sparked extensive debate, making it a crucial strategic issue in education systems worldwide in recent years (Fahmi, 2009). Ensuring quality and obtaining certification are essential responsibilities and priorities for institutions. Universities can accomplish their objectives of meeting the requirements of students, communities, and stakeholders regarding high-quality education, training, and research by engaging in quality assurance activities, thereby enhancing their standing. Quality assurance standards and accreditation are the most effective ways to assess the degree of quality of educational services. Quality assurance aids in identifying issues and constraints that need to be rectified and resolved before implementation. Implementing quality assurance and accreditation is a crucial factor contributing to the success of most higher education institutions globally (Seyfried & Pohlenz, 2018).\n\nQuality assurance is a contemporary principle within the Total Quality Management (TQM) framework. This serves as a means for firms to identify strategies to enhance and advance overall workforce performance. Total quality (TQ) is a component of Total Quality Management (TQM) in education. The TQ, or Total Quality, is a collection of standards and procedures for enhancing educational products. It encompasses technical requirements, the desired attributes of educational products and processes, and the necessary procedures to meet these specifications. Quality assurance encompasses all activities for evaluating and enhancing the value of one or more standards during implementation. The organization guarantees that the products or services adhere to the established quality standards. Total Quality (TQ) is an essential component of quality management that aims to assure individuals and communities by ensuring that quality criteria are met (Hanh, 2020).\n\nThe contemporary notion of Total Quality Management (TQM) in educational institutions has demonstrated that quality assurance in higher education is an ongoing and systematic procedure for evaluating quality based on predetermined criteria and standards. Hanh (2020) mentioned several indicators of higher education quality assurance, including\n\n1. Strategic management: This metric assesses a university’s development and implementation of its long-term plans and objectives. Strategic leaders are responsible for assessing the current state of higher education institutions, evaluating their strengths and weaknesses, and developing strategic plans that encompass the organization’s vision, mission, and educational objectives. These plans guide an institution’s short- and long-term actions.\n\n2. Quality management methods: This metric evaluates the capacity of educational institutions to deliver services that align with the expectations of society, employees, students, job market, and other stakeholders.\n\n3. The marketing and customer service indicators identify societal needs, labor market trends, and learners to offer successful and suitable training and educational services.\n\n4. Human resource development: This metric encompasses the ongoing training of personnel to enhance their ability to efficiently perform tasks and achieve optimal productivity.\n\n5. The equal opportunity indicator ensures that educational institutions and the job market provide equal opportunity. This leads to higher employee and unit satisfaction, and improves labor productivity and quality.\n\n6. Health and safety: Maintaining a healthy and safe environment for employees, students, and beneficiaries is a crucial measure of an educational institution’s performance.\n\n7. Contact management: This metric requires educational institutions to fulfill the requirements of both students and employees and effectively disseminate information across all levels of the organization.\n\n8. Consulting services: This indicator pertains to activities related to organizational governance that aim to identify the requirements of diverse learners (including psychological, academic, and social needs) and devise strategies to fulfill them.\n\n9. Program design and implementation: Learning programs should be developed according to the requirements of the job market and student demands.\n\n10. Certificate of rank: This indicator verifies that students receive qualifications that align with their capabilities.\n\nBy incorporating the above criteria and indicators, developing a set of key performance indicators is a systematic approach for ensuring quality in higher education. The ultimate objective is to produce superior outcomes that align with societal and labor market demands while also ensuring customer satisfaction in the long run. Colleges frequently establish their reputations by obtaining accreditation certificates that validate their commitment to ensuring the quality of their graduates when they enter the job market. Various educational theorists have proposed numerous views of accreditation. However, they unanimously concur that accreditation is a systematic process within an organization that seeks to advance and enhance educational institutions and their programs (Seyfried & Pohlenz, 2018). Accreditation is an indicator of the quality of education management in higher education as a whole, and international ranking agencies require international accreditation to measure higher education performance. Therefore, a change leader must realize the importance of maintaining the quality of education to increase competitiveness at his university.\n\nPromoting internationalization as a crucial policy for education reform can enhance the potential and competitive advantage of higher education institutes to compete nationally and internationally. Internationalization is frequently incorporated as a strategic approach in colleges, representing a robust endeavor by university administrators to enhance their standing in the global market. The primary determinant of this pattern is the worldwide assessment of educational establishments facing global rivalry (Engwall, 2016). Internationalization is an ongoing effort with an evolutionary quality or the development of concepts (Knight, 2008).\n\nBy the mid-1990s, Knight (1994) introduced an organizational process or approach to internationalization at the institutional level had been introduced by Knight (1994), defining internationalization as “the process of integrating international and intercultural dimensions into teaching, research, and institutional service functions.” This definition has been widely used to describe internationalization (Guo & Guo, 2017; Ota, 2018). However, this definition is limited to the institutional dimension. Knight (2008) proposes a new definition, which states that internationalization at the national, sector, and institutional levels integrates intercultural or global dimensions into the purposeful functioning of higher education. In addition, Hudzik (2014) provides a more comprehensive definition of internationalization, defining it as deliberate institutional commitments and actions to embed and integrate international, global, and comparative content and perspectives across higher education teaching, research, and service missions. Beyond the basic functions of such institutions, Hudzik argues that a comprehensive approach is the desire to integrate internationalization into the ethos, values, and institutional mission of higher education (Hudzik, 2014). Furthermore, Hudzik emphasized that for “comprehensive Internationalization, it is important to understand by leaders of universities, government, faculty, students, and all academics, as well as other support service units (Hudzik, 2011).\n\nAccording to Knight and Hudzik’s definition, internationalization is a complex and diverse process that incorporates international, intercultural, and global elements into the functions and goals of higher education institutions. Its purpose is to enhance the quality of education and research for all students and staff, while making significant contributions to society (Guo & Guo, 2017). Therefore, the internationalization program must be designed to be compatible with the internal structure or existing educational and research activities to improve the international image of the university externally without fundamentally changing its substance, because internationalization is not a stand-alone goal or objective, but aims at the reform of universities for quality improvement from a global point of view through internationalization is the way and process to realize competitive advantage during global competition (Ota, 2018). A leader of change who wants to compete on an international scale cannot ignore the internationalization factor.\n\nRivals are crucial in determining a market’s focus and approach (Kohli & Jaworski, 1990; O’Dwyer & Gilmore, 2017; Sukoco et al., 2021). Organizations with the capacity to discern opportunities and dangers from external entities can predict development and establish strategies to adjust to change (Slater, Mohr, & Sengupta, 2014). It is imperative to embrace a market orientation within an organization as the initial step towards a transformative process (Lafferty & Tomas M. Hult, 2001; Narver, Slater, & Tietje, 1998; Sukoco et al., 2021) Klarner et al. (2007) contend that companies should possess the capacity to be highly responsive in order to adjust to changes, particularly in the market effectively. Adaptability can be assessed by a heightened capacity to obtain information regarding present and forthcoming market circumstances (Najafi-Tavani, (Najafi-Tavani, Sharifi, & Najafi-Tavani, 2016). Market demand fluctuations prompt enterprises to prioritize data acquisition for evolving customer demands, interests, and behavior. This enables them to deliver exceptional customer value by leveraging diverse information sources (Narver & Slater, 1990). Engaging in activities to acquire and analyze market information will facilitate the cultivation of a culture of learning inside firms (Deshpandé, Farley, & Webster, 1993; Deshpande & Webster, 1989).\n\nLeaders who embrace market orientation actively solicit prompt consumer input and provide unrestricted access to extensive information for all organization members (Jaworski & Kohli, 1993; Pinho, Rodrigues, & Dibb, 2014). The unrestricted availability of information within the organization enables personnel to acquire and embrace new knowledge about the market, thereby improving and refreshing their skills and understanding throughout the organization. This empowers them to consistently make proper decisions and take necessary action (Minucci, 2016). This subsequently generates additional value for customers (Liu et al., 2002) and optimizes the service delivery process more effectively and efficiently (Siggelkow & Terwiesch, 2019).\n\nMoreover, leaders in companies must devise methods to establish a collective understanding (Gebhardt, Carpenter, & Sherry, 2006) and enhance cohesion to establish a mechanism for collective transformation (Liu & Atuahene-Gima, 2018). Market orientation in non-profit organizations aligns the organization’s attention towards external factors such as stakeholders, thereby consolidating the organization’s emphasis on crucial external elements (Modi, 2012) and internal constituencies. In addition, universities involve numerous stakeholders who can shape organizational policies (Mainardes, Alves, & Raposo, 2012). The institution prioritizes customer orientation towards students and the community, who are recognized as stakeholders. Students immediately utilize and benefit from the products and services offered by the university (Akonkwa, 2009); higher education is widely seen by society as an institution that safeguards and perpetuates sources of knowledge (Lu & Etzkowitz, 2008), the organization is anticipated to play an active part in the process of transforming knowledge into commercial products and services within the innovation value chain (Urbano & Guerrero, 2013).\n\nConsequently, institutions should be attentive and adaptable to the desires of students and society, offering the options that they seek (Nixon, Scullion, & Molesworth, 2010). Colleges prioritizing customer satisfaction can oversee service operations, distribute essential information to all stakeholders, and actively strive to meet their demands (Hammond, Webster, & Harmon, 2006). This method establishes an environment favorable for colleges that prioritizes market-oriented approaches (Nagy & Berács, 2012). Universities that possess the ability to offer genuine and groundbreaking services while being cognizant of the requirements of their consumers, including students and the community, can collaboratively design new service formats and foster a culture that prioritizes customer satisfaction (Dollinger & Lodge, 2020; Dollinger & Vanderlelie, 2021; Sukoco et al., 2021).\n\nOrganizations that effectively adapt to the accelerating pace of change must consider customer preferences and competitive actions (De Luca & Atuahene-Gima, 2007). To achieve a comprehensive implementation of change and strategy across the entire organization, it is necessary to disseminate them sequentially (Klarner et al., 2007). Organizations with robust interfunctional coordination exhibit efficient communication and collaboration among several departments (Marsh & Stock, 2003). To foster a unified culture that maximizes the use of market intelligence for institutional progress (Gebhardt et al., 2006). Leaders in higher education who can capitalize on opportunities in the commercial aspects of higher education are expected to produce revenue from non-academic activities. The perception of higher education as an institution has shifted, recognizing it as a crucial catalyst for economic growth and development (Taib & Abdullah, 2015).\n\nSince the outset, it has been universally acknowledged that universities’ primary function is to serve as a facilitative instrument to foster economic growth and development. Nevertheless, modern colleges are embracing a more business-oriented approach to foster and facilitate economic growth. With the emergence of a new paradigm, universities have transformed into entrepreneurial institutions, actively engaging in the commercialization of research and adopting a proactive stance towards the role of academic research in the marketplace. This paradigm emphasizes that the environmental forces of a hypercompetitive global environment have transformed the university’s mission of research, teaching, and service. The increasing number of “business-like” higher education institutions worldwide puts pressure on universities to become more entrepreneurial and achieve higher efficiency in improving quality (Ajayan & Balasubramanian, 2020). Recent developments in financial autonomy granted by the government to several universities for financial management flexibility, especially to state universities, have several consequences, such as reducing government subsidy funds, which means that autonomous universities must generate some alternative income independently (Amran & Muhammad, 2014). This is in line with managerial, which requires universities to be more entrepreneurial and find alternative income mechanisms in universities (Ajayan & Balasubramanian, 2020).\n\nSome researchers have determined that universities can adapt to and become entrepreneurial universities (Clark, 1998; Sporn, 2001). Clark (2000) argued that many universities should become more proactive and entrepreneurial. The primary emphasis of the university’s entrepreneurship center lies in exploring innovative approaches to earn revenue and is seamlessly incorporated into the strategic planning framework of collaborating institutions. The primary responsibility of the entrepreneurship center is to execute strategic initiatives about fundraising and engage external specialists to transform concepts, typically originating from students and research endeavors, into commercially viable goods. Hence, entrepreneurship has the potential to stimulate trade and business collaboration and facilitate the provision of research and consulting services from partner universities to both public and private entities (Fahmi, 2009).\n\nAnother assumption that universities are increasingly entrepreneurial is the consequence of granting autonomy to the government, which results in a reduction in public funds by the government by removing subsidies and giving total confidence that universities have been able to be independent regardless of government control (Gaus, 2019a). Therefore, universities cannot only rely on income from the primary sector, namely academic income, but must also develop a pattern of partnership/collaboration to obtain funding from the non-academic business sector. The ability of a change leader to optimize all additional business potential from non-academic pathways greatly determines the sustainability of the university he leads. Each university’s adaptability in adjusting to technological developments/digitalization in education provision cannot be ruled out.\n\nDigitalization concerns using technology to renew, simplify, and increase processes, tasks, and products (Tomte, Fossland, Aamodt, & Degn, 2019). In the last decade, all aspects of life and business operations have been significantly transformed by digital technology. An organization’s digital transformation principally concerns the adoption of technology portfolios such as the Internet of Things (IoT), digital platforms, social media, Artificial Intelligence (AI), Big Data, and Machine Learning (ML) ((Antonopoulou, Halkiopoulos, Barlou, & Beligiannis, 2021; Foerster-Metz, Marquardt, Golowko, Kompalla, & Hell, 2018; Khalid et al., 2018; Matalamäki & Joensuu-Salo, 2021). On a broad scale, the shift to modern technology has brought about new competitive mechanisms, structures, work systems, and interactions. On a smaller scale, digitalization impacts the dynamics, processes, skills, and competencies required by all members of the organization, regardless of their position (Cascio & Montealegre, 2016; Rienties, Brouwer, & Lygo-Baker, 2013).\n\nThe process of digitalization in education encompasses a wide range of factors that contribute to its quality, including organizational matters, technology infrastructure, and pedagogical methods (Cascio & Montealegre, 2016; Selwyn, 2011), and it influences internationalization by offering more flexible online education programs (Conole, 2014). In addition, digitalization provides conveniences such as administrative solutions, data security systems, systems to detect fraud and plagiarism, research data storage, library services, and various learning resources as well as opportunities for better collaboration across campuses (Khalid et al., 2018).\n\nDigitalization has significantly changed higher education due to technological developments and globalization. Universities’ ability to rapidly increase digitalization will affect their ability to survive global competition, especially in internationalization, student mobility, funding, and world ranking positions (Khalid et al., 2018). This is in line with previous research (Wu, Yeniyurt, Kim, & Cavusgil, 2006) showing that Information Technology (IT) can contribute to network collaboration and strengthen an organization’s competitive capabilities. College leaders must recognize the need to evolve and reshape structures, processes, pedagogic practices, curricula, and innovation. Meanwhile, there is no innovation without collaboration. This is in line with Luthans (1988), who states that the success of a leader depends on his ability to build networking.\n\nThe resulting innovation performance excellence in collaboration depends on the ability to manage networking (Ter Wal et al., 2020). Networking is a set of relationships connecting people inside and outside an organization that can be relied upon to succeed in work (Altbach, 2011). Collaboration with strategic partners is urgently required to address the challenges of neoliberalism. Social capital theory states that networks are a power source for individuals and organizations (Timberlake, 2012). Networking can potentially increase career success for individuals, such as raises, promotions, career satisfaction, employment opportunities, job performance, social support, resources, and professional support (Seibert, Kraimer, & Liden, 2001). In addition, Luthans (1988) asserts that managers’ ability to build networks is the strongest predictor of managerial success that benefits both individuals and organizations. McGuire (2000) states that formal networks are public, official, and have clear boundaries, whereas informal networks are private, voluntary, and characterized by fluid boundaries. Employers usually formally recognize formal work networks, focus on achieving the goals of members and social organizations, and tend to have identifiable membership and network structures (McGuire 2000). By contrast, participation in informal networks is not formally regulated, and the purpose of such networks may be work-related, personal, or social (Ibarra, 1992). The formation of networks by university leaders is expected to increase the internationalization activities of higher education by easily obtaining various information and other resources from outside the organization.\n\nThis generation of leadership encourages universities to compete globally (Angreani & Vijaya, 2017). Indicators of success in achieving competitive universities are reflected in the achievement of positions in international rankings/World Class Universities (Polyakov et al., 2020). The importance of leadership towards the WCU in a university setting is reflected in the expectations of national and international accreditation bodies. Each includes criteria and policies related to leadership (Burns & Mooney, 2018). Therefore, WCU leaders must have global networking, in which they work in a complex, fast-changing, and often ambiguous international environment. WCU leaders engage in foreign markets, strategize internationally, and manage and motivate teams to compete globally (Hassan et al., 2011).\n\nHigher education leaders in the era of neoliberalism not only play academic leaders but also have two roles simultaneously, namely as academic leaders and chief executive officers at the universities they lead (Ekman, Lindgren, & Packendorff, 2018; Nizam, 2022). Leadership plays an important role in determining the success of higher education (Osseo-Asare et al., 2005). This is reflected in the expectations of Accreditation Bodies (National and International), including the criteria and policies related to effective leadership in higher education (Mooney, Burns, & Chadwick, 2012).\n\nThe success of a change depends on the leader’s leadership style (Baesu & Bejinaru, 2014). Leadership style has been recognized as an important aspect of influencing innovation because leaders effectively have an important role in producing ideas, goal setting, and creating organizational culture (Elrehail, Emeagwali, Alsaad, &; Alzghoul, 2018). In addition, leadership and behavior can build a climate of trust that encourages innovation throughout the organization (Al-Husseini &; Elbeltagi, 2014). To manage these changes, leaders must understand the change management process and demonstrate an appropriate leadership style (Akinbode &; Shuhumi, 2018; Mansaray, 2019; McRoy & Gibb, 2009). Transformational leadership is believed to be a key element of change-oriented leadership (Akinbode &; Shuhumi, 2018; Appelbaum et al., 2015), and to understand higher education governance in a period of transformation into the priority of a change leader (Aldulaimi &; Abdeldayem, 2020).\n\n\nConclusions\n\nAfter conducting a bibliometric analysis of 662 documents, we discovered that most documents (446) were articles, with the remainder coming from books, chapters, conference papers, editorials, notes, and reviews. The journals that made the most significant contributions to the development of collegiality, change management, and neoliberalism in Higher Education are International Journal of Educational Management (15 documents), Journal of Higher Education Policy and Management (11 documents), Tertiary Education and Management (10 documents), Higher Education (9 documents), Innovations in Education and Teaching International (9 documents), and Journal of Organizational Change Management (9 documents).\n\nFurthermore, there has been a steady increase in articles published annually, with notable spikes in 2017 and 2018 regarding collegiality, change management, and neoliberalism in higher education. The top contributors to publications on collegiality, change management, and neoliberalism in higher education are institutions: Monash University (27 documents), University of The Sunshine Coast (18 documents), University of Massachusetts (10 documents), Curtin University (9 documents), Edinburgh Napier University (nine documents), Kennesaw State University (eight documents), University of Oulu (eight documents), Macquarie University (seven documents), National University of Science and Technology (Misis) (seven documents), and Texas A and M University (seven documents). Institutions from Australia and America still dominate most affiliations related to the relationship between these factors in higher education, while authors from the United Kingdom, the USA, and Australia dominate correspondence institutions. From the publications, it can be concluded that the authors have the most significant relevance in a row, namely, Lazano R. and Tapper T. (six documents), Amaral A., Carvalho T., and Palfreyman D. (five documents), Angehrn AA, Maxwell K. (four documents), Ameen K, Awais S., and Blackmore J. (three documents). The keywords in the word cloud regarding collegiality, change management, and neoliberalism in higher education are organization and management, leadership, curriculum, organizational innovation, organizational change, decision-making, and humans, indicating that the relationship between these concepts is relevant to leadership, organizational change, management, and human resources. The article also added eight issues that can be considered in instituting changes in higher education related to adopting neoliberalism in higher education. How far and how much corrosive impact is created by the adoption of the neoliberal environment, of course, should not rule out the prominent role that is the common goal of higher education, which is to carry out the social function of higher education to create the welfare of the nation, through the development of science and technology and producing intellectuals, scientists, or highly competitive professional human resources.\n\nThis study is limited to case studies and critical analyses of literature. There may be a risk of publication bias because the study only included published articles indexed in Scopus, potentially overlooking non-indexed research that could provide different perspectives. Further research is necessary for testing the robustness of the findings to different scenarios, such as excluding studies at high risk of bias or adjusting for publication bias, we can assess the reliability and validity of the synthesized results in the presence of reporting bias.\n\nFurther research can be conducted to empirically examine the factors that significantly influence change in universities in the face of the influence of neoliberalism and to examine the extent to which the perspective of university leaders and management considers these factors important for increasing the competitiveness of universities. Although the study results have been presented in this way, there are limitations to revealing various things that may be related beyond the eight issues the authors report. Future research can delve deeper into other factors that influence the implementation of neoliberalism in higher education. Future research could also empirically examine to what extent the influence of these eight issues affects the policy patterns of a change leader in higher education. The future research could conduct GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach for assessing the certainty of evidence and grading the strength of recommendations in systematic reviews. This method provides a transparent and structured framework for evaluating the quality of evidence and informing decision-making. The upcoming research may also conduct the effect measure on performance metrics to assess the alignment of educational services with stakeholder expectations before and after the impact of neoliberal policies on higher education institutions. This effect measure provides a framework for evaluating the impact of neoliberalism on collegiality, governance, management, and quality management methods within the context of higher education institutions.",
"appendix": "Data availability\n\nZenodo: Explicating collegiality and change management in neoliberalism during the dynamics of higher education institutions. https://doi.org/10.5281/zenodo.10730018 (Marlia et al., 2024).\n\nThis project contains the following underlying data:\n\n- Scopus.csv\n\n- Scopus.ris\n\nZenodo: Explicating collegiality and change management in neoliberalism during the dynamics of higher education institutions. https://doi.org/10.5281/zenodo.10730018 (Marlia et al., 2024).\n\nThis project contains the following extended data:\n\n- Figure 1-Concept Map of Changes in Universities.png\n\n- Figure 2-Primary Information.png\n\n- Figure 3-Annual Scientific Production.png\n\n- Figure 4-Average Article Citation per Year.png\n\n- Figure 5-Most relevant sources.png\n\n- Figure 6-Sources’ local impact by H-index.png\n\n- Figure 7-Most relevant authors.png\n\n- Figure 8-Authors’ production over time.png\n\n- Figure 9-Most relevant affiliations.png\n\n- Figure 10-Corresponding author’s countries.png\n\n- Figure 11-Co-occurance network.png\n\n- Figure 12-Word cloud.png\n\n- Figure 13-Tree map.png\n\n- Figure 14-Comprehensive change patterns.png\n\nPRISMA Checklist for ‘Explicating collegiality and change management in neoliberalism during the dynamics of higher education institutions’ https://doi.org/10.5281/zenodo.10730018 (Marlia et al., 2024).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nWe thank two anonymous Professors as invited reviewers for their comments, suggestions and data interpretation. 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Publisher Full Text\n\nNasution VIA, Prasojo E, Jannah LM, et al.: Governance of Autonomous Higher Education Institution toward World-Class University: A Case Study at the Universitas Indonesia. Journal of Critical Reviews. 2020; 7(10).\n\nNickson A: A Qualitative Case Study Exploring the Nature of New Managerialism in UK Higher Education and Its Impact on Individual Academics’ Experience of Doing Research. Journal of Research Administration. 2014; 45(1).\n\nNixon E, Scullion R, Molesworth M: How choice in higher education can create conservative learners. The Marketisation of Higher Education and the Student as Consumer. 2010.\n\nNizam: Nakhoda menuju universitas kelas dunia. Jakarta: UI Publishing; 2022.\n\nO’Dwyer M, Gilmore A: Competitor orientation in successful SMEs: an exploration of the impact on innovation. Journal of Strategic Marketing. 2017; 27: 21–37. Publisher Full Text\n\nOreg S, Vakola M, Armenakis A: Change Recipients’ Reactions to Organizational Change. The Journal of Applied Behavioral Science. 2011; 47(4): 461–524. Publisher Full Text\n\nOsborne D, Gaebler T: Reinventing Government. New York, NY: Penguin Press; 1992.\n\nOsseo-Asare AE, Longbottom D, Murphy WD: Leadership best practices for sustaining quality in UK higher education from the perspective of the EFQM excellence model. Quality Assurance in Education. 2005; 13(2): 148–170. Publisher Full Text\n\nOta H: Internationalization of Higher Education: Global Trends and Japan’s Challenges. Educational Studies in Japan. 2018; 12: 91–105. Publisher Full Text\n\nPinho JC, Rodrigues AP, Dibb S: The role of corporate culture, market orientation and organisational commitment in organisational performance: The case of non-profit organisations. Journal of Management Development. 2014; 33(4): 374–398. Publisher Full Text\n\nPolyakov M, Bilozubenko V, Korneyev M, et al.: Analysis of key university leadership factors based on their international rankings (QS World University Rankings and Times Higher Education).Problems and Perspectives in Management.2020; 18(4): 142–152. Publisher Full Text\n\nPrice ADF, Chahal K: A strategic framework for change management. Construction Management and Economics. 2006; 24(3): 237–251. Publisher Full Text\n\nPrysor D, Henley A: Boundary spanning in higher education leadership: identifying boundaries and practices in a British university. Studies in Higher Education. 2018; 43(12): 2210–2225. Publisher Full Text\n\nRienties B, Brouwer N, Lygo-Baker S: The effects of online professional development on higher education teachers’ beliefs and intentions towards learning facilitation and technology. Teaching and Teacher Education. 2013; 29(1): 122–131. Publisher Full Text\n\nRobertson SL: Corporatisation, competitiveness, commercialisation: New logics in the globalising of UK higher education. Globalisation, Societies and Education. 2010; 8(2): 191–203. Publisher Full Text\n\nSeibert SE, Kraimer ML, Liden RC: A social capital theory of career success. Academy of Management Journal. 2001; 44(2): 219–237. Publisher Full Text\n\nSelwyn N: Education and Technology: Key Issues and Debates. Neurological sciences: official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2011.\n\nSeyfried M, Pohlenz P: Assessing quality assurance in higher education: quality managers’ perceptions of effectiveness. European Journal of Higher Education. 2018; 8(3): 258–271. Publisher Full Text\n\nSiggelkow N, Terwiesch C: The Age of Continuous Connection. (cover story). Harvard Business Review. 2019; 97(3).\n\nSlater SF, Mohr JJ, Sengupta S: Radical product innovation capability: Literature review, synthesis, and illustrative research propositions. Journal of Product Innovation Management. 2014; 31(3): 552–566. Publisher Full Text\n\nSmith R: Departmental Leadership and Management in Chartered and Statutory Universities: A Case of Diversity. Educational Management Administration & Leadership. 2005; 33(4): 449–464. Publisher Full Text\n\nSporn B: Building adaptive universities: Emerging organisational forms based on experiences of european and us universities. Tertiary Education and Management. 2001; 7(2): 121–134. Publisher Full Text\n\nSukoco BM, Choirunnisa Z, Mudzakkir MF, et al.: Market orientation and capacity for change in higher education performance in Indonesia. Journal of Asia Business Studies. 2021; 16: 80–100. Publisher Full Text\n\nTaib FM, Abdullah MNLY: Governance Reforms in Public University of Malaysia. 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}
|
[
{
"id": "281536",
"date": "18 Jun 2024",
"name": "Elias Said-Hung",
"expertise": [
"Reviewer Expertise My research areas are in the sociology of education",
"sociology of communication",
"hate speech",
"disinformation content",
"and polarization. Most of my research is based on quantity analysis and systematic reviews",
"amongst others."
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt is an interesting work, but it lacks adjustments that could help improve its exposition. First of all, I consider that the abstract of the work needs to be reviewed and better structured. The methodology, objectives, results, and relevant conclusions should be more precise.\nSecondly, the work's title should be reviewed, making it clear that it is a literature review.\nThirdly, the location of the research question should be reviewed. I find it strange that it is stated between the introduction and the literature review. It makes more sense for it to be part of the final paragraph of the introduction section.\nFourthly, the study should review its general objective to make it more straightforward regarding the type of research carried out. The paper focuses on describing the changes in universities owing to the ideology of neoliberalism through the systematic review, but the results aim to better understand how, from where, and in what academic spaces this topic has been addressed. Something that is not the same. The specific objectives of the study would also need to be made clear so that the presentation of the data has a more coherent narrative, which helps to achieve the general objective finally proposed. Thus, it is better to understand the impact of showing the h-index of the journals where these works are published, for example. Honestly, I consider that the objective of this work focuses more on understanding the frontiers of knowledge reached around the proposed topic than what is proposed as a general objective. Something that can be useful to identify dominant conceptual and methodological approaches better and identify strengths and weaknesses within the academic debate around the topic raised, which helps the development of new works.\nFifthly, the methodological framework should be better reviewed. The type of methodology considered for the final sample analysis selection should be made clear. In addition to better understanding the selection criteria taken. I understand that a Prisma or similar methodology was applied, but it is something that is not clear. The lack of clarity of specific objectives contributes to the methodology not being transparent about the central categories considered and the convenience of the data described in the results section.\nSixth, the discussion should be reviewed, considering all the recommendations given. The conclusion section is missing. The discussion and conclusions should clarify the data's implications in light of the theoretical framework, practical applications, limitations, and future lines of work.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Partly\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Partly\n\nIs the statistical analysis and its interpretation appropriate? 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.) Yes",
"responses": [
{
"c_id": "12718",
"date": "04 Nov 2024",
"name": "Makna Ani Marlia",
"role": "Author Response",
"response": "The abstract's structure is based on the author’s guidelines. Thanks for correcting our title; we revised the title. The position of the research questions is placed in the last paragraph of the Introduction. The study's specific objective is to explore and clarify the role of collegiality and change management within the context of neoliberalism in higher education institutions. This objective is achieved through a systematic literature review that examines how these institutions navigate and adapt to dynamic environments influenced by neoliberal policies. We added implications in the light of theoretical framework and practical application at the end of the conclusion section. We made the limitations and future research direction stand-alone after the conclusion section."
}
]
},
{
"id": "307169",
"date": "26 Aug 2024",
"name": "Javad Pourkarimi",
"expertise": [
"Reviewer Expertise Educational Management"
],
"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\nThanks to the scientific efforts of the authors; It seems that the researcher should pay attention to more details both in the aspect of problem analysis and in the aspect of methodology, which I will raise two points below: The researcher should clearly show what was the existing problem based on which he designed the research. Examine and display the relevant evidence carefully and design it as a scientific research to be able to present the argument well. To conduct a systematic study, the researcher must show that enough research has been done in the desired field and the researcher intends to systematically review those studies; Provide a different and creative representation. In addition, there are various types of systematic review that the researcher can refer to the following address- [1]\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? No\n\nIs the statistical analysis and its interpretation appropriate? Partly\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": "12719",
"date": "04 Nov 2024",
"name": "Makna Ani Marlia",
"role": "Author Response",
"response": "We selected PRISMA for our systematic literature review because systematic reviews can report methods and results in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. We changed the title of this paper."
}
]
}
] | 1
|
https://f1000research.com/articles/13-237
|
https://f1000research.com/articles/13-153/v1
|
01 Mar 24
|
{
"type": "Study Protocol",
"title": "Investigation of reporting bias in interrupted time series (ITS) studies: a study protocol",
"authors": [
"Phi-Yen Nguyen",
"Simon Turner",
"Elizabeth Korevaar",
"Andrew Forbes",
"Matthew J. Page",
"Joanne E. McKenzie",
"Phi-Yen Nguyen",
"Simon Turner",
"Elizabeth Korevaar",
"Andrew Forbes",
"Matthew J. Page"
],
"abstract": "Background Systematic reviews that aim to synthesize evidence on the effects of interventions targeted at populations often include interrupted time-series (ITS) studies. However, the suppression of ITS studies or results within these studies (known as reporting bias) has the potential to bias conclusions drawn in such systematic reviews, with potential consequences for healthcare decision-making. Therefore, we aim to determine whether there is evidence of reporting bias among ITS studies.\n\nMethods We will conduct a search for published protocols of ITS studies and reports of their results in PubMed, MEDLINE, and Embase up to December 31, 2022. We contact the authors of the ITS studies to seek information about their study, including submission status, data for unpublished results, and reasons for non-publication or non-reporting of certain outcomes. We will examine if there is evidence of publication bias by examining whether time-to-publication is influenced by the statistical significance of the study’s results for the primary research question using Cox proportional hazards regression. We will examine whether there is evidence of discrepancies in outcomes by comparing those specified in the protocols with those in the reports of results, and we will examine whether the statistical significance of an outcome’s result is associated with how completely that result is reported using multivariable logistic regression. Finally, we will examine discrepancies between protocols and reports of results in the methods by examining the data collection processes, model characteristics, and statistical analysis methods. Discrepancies will be summarized using descriptive statistics.\n\nDiscussion These findings will inform systematic reviewers and policymakers about the extent of reporting biases and may inform the development of mechanisms to reduce such biases.",
"keywords": [
"reporting bias",
"publication bias",
"selective reporting",
"outcome reporting",
"research methods",
"meta-research",
"interrupted time series",
"discrepancies in reporting"
],
"content": "Introduction\n\nAn interrupted time series (ITS) study is a non-randomized design, commonly used to evaluate interventions targeted at populations (e.g., introduction of tobacco plain packaging laws on the number of calls to smoking cessation helplines)1 when randomized trials are not practical, and in some circumstances, ethical. This design can be less susceptible to bias than other non-randomized designs, such as before-after designs.2–5 The use of ITS designs in public health has been increasing with time,6–8 but has gained particular prominence during the COVID-19 pandemic to evaluate the effectiveness of COVID-19 reduction strategies (e.g., lockdowns),9,10 as well as their impact on non-COVID-19 conditions.11–13\n\nIn an ITS study, measurements of an outcome variable are often collected continuously over time and aggregated (using summary statistics such as counts or proportions) within, generally, regular time intervals (e.g., weekly, monthly) for analysis. The ‘interruption’ separates the time series into pre- and post-interruption segments. The underlying time trend in the pre-interruption segment can be estimated and used to predict what would have occurred in the post-interruption period had the interruption not occurred (referred to as the ‘counterfactual’). Differences between the predicted trend and the observed post-interruption trend can be used to quantify the effects of the interruption, such as an immediate change at the time of interruption (‘level change’) or the change in slope between pre- and post-interruption (‘slope change’).4,14,15\n\nSystematic reviews may be undertaken to collate and synthesize evidence on the effects of interventions. In reviews that examine the effects of policy interventions, ITS studies are likely to be eligible because evidence from randomized trials may be limited or unavailable. A key factor underpinning the validity of the findings from systematic reviews is the extent to which the included studies (and their results) are representative of missing studies, a concept known as reporting bias.\n\nThe extent of the reporting bias among ITS studies is unknown. Reporting bias can arise when there is suppression of entire studies (known as publication bias) or results within studies that are unfavorable to the study hypotheses (known as selective reporting bias) due to the nature of the results themselves (i.e., based on their direction, magnitude, or P-value).16,17 Reporting bias has the potential to bias conclusions drawn in systematic reviews (with or without meta-analyses), with potential consequences for healthcare decision-making.18–20 Unlike randomized trials, where prospective registration is required by ethics committees and journals,21,22 and many trial registries exist, such requirements and registries do not exist for ITS studies.23,24 As a result, the same drivers are not in place to prespecify outcomes and analysis plans, or to publish unfavorable results of ITS studies. Therefore, reporting bias may exist to a greater extent in ITS studies.\n\nTherefore, we aim to determine the extent of reporting bias among ITS studies based on the following three objectives:\n\n1. To examine whether the publication of ITS studies is influenced by their results (i.e., publication bias).\n\n2. To examine (i) whether there are discrepancies between outcomes specified in protocols of ITS studies and reports of their results and (ii) whether there is evidence of selective result reporting among ITS studies.\n\n3. To examine whether there are discrepancies in the reporting of methods between protocols and reports of ITS studies\n\n\nProtocol\n\nEach of these objectives will be addressed in a separate analysis (Figure 1).\n\n\nCreating a database of ITS study protocols and reports of their results\n\nWe will conduct a search for published protocols of ITS studies indexed in three bibliographic databases (PubMed, MEDLINE, and Embase via Ovid) and in the JMIR Research Protocols, each from inception to December 31, 2022. For bibliographic databases, we will use a sensitivity-maximizing search filter developed by our team for ITS studies.25\n\nEligible protocols include protocols and statistical analysis plans of ITS studies, including studies that plan to conduct ITS analysis alongside other planned analyses (e.g., qualitative analysis or cost-effectiveness modelling). For the purpose of our study, an ITS study is defined as one in which (a) there are at least two segments separated by a clearly defined interruption (i.e., an intervention or an exposure), (b) there are at least three data points for at least two of the segments, and (c) each data point represents a summary statistic (e.g., mean and rate) of individual observations collected from a group of individuals (e.g., within a country, state, hospital, or other unit) within a period of time (e.g., weekly or monthly). Both controlled and uncontrolled ITS studies will be considered eligible. We will only include ITS study protocols written in English.\n\nOne author (PYN) will screen all titles, abstracts, and potentially eligible full-text reports. A 10% random sample of full-text reports deemed ineligible and all full-text reports deemed eligible by the first author will be independently screened by the second author (JEM, ST, EK, or MJP). Discrepancies will be resolved through discussion between the authors or through team discussions.\n\nFor each ITS study protocol meeting the inclusion criteria for our study, we will search for corresponding report(s) of the results using the following approaches1: searching in Ovid MEDLINE and Embase for the study’s title and acronyms, trial registration number (if reported), and any co-author publications between the first author and last author2; checking for updates on registration sites, such as ClinicalTrials.gov; and3 using forward citation searching tools, such as Web of Science’s Cited Reference Search. For the purpose of this study, ‘report(s) of the results’ are defined as any peer-reviewed report that provides quantitative results for any outcome collected as part of the ITS. Other reports related to this study that present results for data not collected as part of the ITS will not be included. Methods paper utilising results from an ITS study will be excluded if not referenced in the protocol. If multiple eligible reports of results are found, we will include all of them. For each protocol, we will search for a report of the results only if at least 6 months have passed since the date of completion of data collection (as stated or implied in the ITS study protocol), or if not specified, after the date of publication of the protocol. We will not search for results if recruitment or data collection are confirmed to be ongoing at the time of the search.\n\nWe will begin by searching for protocols and reports of their results published up to December 31, 2022. This search will be updated once every six months until the time of analysis for each project, up to December 2023.\n\n\nData collection\n\nData extraction will be conducted using standardized extraction forms created in the Research Electronic Data Capture (REDCap)26 hosted at Monash University. Information will be collected from the protocols and reports of the results (and all their supplementary files) and journal websites. Five authors (PYN, JEM, EK, MJP, and ST) will pilot the data extraction forms on five ITS studies to refine the items and achieve a shared understanding of the forms. One author (PYN) will extract the data for the remaining studies, and a second author (JEM, EK, MJP, or ST) will independently extract data for a random sample of 10% of the studies. For any items where we observed a high degree of inconsistency, we will undertake double data extraction for these items on a further randomly selected sample of studies. In addition, we will hold weekly meetings with all the authors to discuss any uncertainty arising during data extraction. Discrepancies will be resolved, and necessary amendments to the data extraction form will be made following these discussions. The data collection forms are summarized in Table 1.\n\n\n\n• Details of corresponding authors\n\n• Details of publication: date of submission, date of publication, name of journal\n\n• Type of funding (government / not-for-profit/industry/undisclosed/no funding)\n\n• Elements constituting the primary interrupted time series (ITS) research question(s): populations/setting, the interruptions, interruption groups and comparator groups\n\n• Whether the study involves analyses other than ITS analysis (e.g. qualitative analysis)\n\n\n\n• Details of publication: date of submission, date of publication, name of journal\n\n\n\n• Whether data collection and analysis has been completed\n\n• Whether a report of the ITS results has been submitted for publication\n\n• Date of submission, rejection or publication of report of the results\n\n• Reasons for not submitting results for publication\n\n• Potential reasons for rejection of the report of results\n\n• Name of journal\n\n\n\n• Eligibility criteria to select participants into the ITS\n\n• Timing of data collection relative to publication of protocol: retrospective /prospective/both\n\n• Start and end dates of the data to be collected\n\n• Source of data (collected by investigating team/collected by an external party)\n\n• Characteristics of all segments in the ITS: start and end date, and number of data points per segment\n\n\n\n• Eligibility criteria to select participants into the ITS\n\n• Timing of data collection relative to publication of protocol: retrospective /prospective/both\n\n• Start and end dates of the data to be collected\n\n• Source of data (collected by investigating team/collected by an external party)\n\n• Characteristics of all segments in the ITS: start and end date, and number of data points per segment\n\n\n\n• Model structure (e.g. whether level change and/or slope change was modelled, whether the impact of the interruption was immediate or delayed, and how the interruption period was incorporated in analysis)\n\n\n\n• Model structure (see details from ‘Data from protocols’)\n\n\n\n• Estimation method (e.g. ordinary least squares, restricted maximum likelihood)\n\n• Method of correcting for autocorrelation\n\n• Method of correcting for seasonality\n\n• Method of correcting for non-stationarity\n\n• Method of handling outliers\n\n• Covariates used for adjustment\n\n• Presence of a control group\n\n• Method of conducting intervention-control group comparison\n\n• Subgroup analysis, if any\n\n\n\n• Estimation method (e.g. ordinary least squares, restricted maximum likelihood)\n\n• Method of correcting for autocorrelation\n\n• Method of correcting for seasonality\n\n• Method of correcting for non-stationarity\n\n• Method of handling outliers\n\n• Covariates used for adjustment\n\n• Presence of a control group\n\n• Method of conducting intervention-control group comparison\n\n• Subgroup analysis, if any\n\n\n\n• List of all planned outcomes\n\n\n\n• Description of outcome\n\n• Whether higher value indicates benefit or harm\n\n• Whether outcome was designated as primary or secondary outcome, or not specified\n\n• Time intervals at which individual-level data were collected\n\n• Time intervals at which data were aggregated for analysis\n\n• Data type of individual-level observations (e.g. dichotomous, continuous)\n\n• Data type of the summary statistic used to aggregate the individual-level observations (e.g. count, percentage)\n\n\n\n• List of all reported outcomes\n\n\n\n• Description of outcome\n\n• Whether higher value indicates benefit or harm\n\n• Whether outcome was designated as primary or secondary outcome, or not specified\n\n• Time intervals at which individual-level data were collected\n\n• Time intervals at which data were aggregated for analysis\n\n• Data type of individual-level observations (e.g. dichotomous, continuous)\n\n• Data type of the summary statistic used to aggregate the individual-level observations (e.g. count, percentage)\n\n\n\n• Reasons for failure to report an outcome\n\n• Reasons for reporting an outcome that was not specified in the protocol\n\n• Reasons for inconsistency in labelling the primary status of outcome\n\n\n\n• List of all planned effect measures\n\n\n\n• Effect estimate\n\n• Measure of precision (confidence interval and level (e.g. 95%), standard error)\n\n• Exact P-value and threshold of statistical significance\n\n• Direction of effect estimate (favouring interruption group/comparator group)\n\n\n\n• List of all reported effect measures\n\n\n\n• Effect estimate\n\n• Measure of precision (95% confidence interval and level (e.g. 95%), standard error)\n\n• Exact P-value and threshold of statistical significance\n\n• Direction of effect estimate (favouring interruption group/comparator group)\n\n\n\n• Statistical significance of the effect estimate at 5% threshold\n\n• Direction of effect estimate (favouring interruption group/comparator group)\n\n• Reason for not reporting or not fully any the results\n\nFrom each ITS study protocol, one author (PN) will identify the primary ITS research question(s), which will be used to determine which results are eligible for our assessment of publication and outcome/result reporting bias (see Box 1 for an example). In determining the primary ITS research question (or questions) from the protocol, we will only consider the population/setting, interruption group(s), and comparator group(s) elements of the research question and not the planned outcomes to be measured. In a simple ITS with one interruption, there is only one comparison that can be made (between the pre- and post-interruption periods); for ITS with multiple interruptions, more than two comparisons are possible (Figure 2). Furthermore, the impact of interruption may be assessed in different populations. In reporting the research questions, authors may or may not be explicit about all elements or comparisons of primary interests. For the purpose of our study, we will use the reported primary question elements to determine which results are eligible for our assessment of publication and result reporting bias (see Box 1 for an example). The primary ITS question elements will be those that are reported by the authors as ‘primary,’ or the first reported in the protocol.\n\n\n\nSuppose an interrupted time series (ITS) has three segments. The first segment is the pre-intervention control; the second is a minimal implementation of intervention A; and, the third is an intensive implementation of intervention A.\n\nThe intervention is evaluated in two populations (population 1 and 2).\n\nIf the authors stated “Our primary aim is to compare the intensive implementation A versus control”, then for our assessment of publication and outcome/result reporting bias, we would consider any results pertaining only to this comparison, but for any population (since the population was not stated in the aim).\n\nIf the authors stated “Our primary aim is to examine the effect of intervention A”, then for our assessment of publication and outcome/result reporting bias, we would consider any result pertaining to the comparisons ‘minimal intervention A versus control’, ‘intensive intervention A versus control’, ‘intensive intervention A versus minimal intervention A’; and, for any population.\n\nFor each ITS study, we will record details of the methods, including the data collection process, model characteristics, and statistical analysis methods, as presented in both the protocol and report(s) of the results. We will record the eligibility criteria to select participants for the ITS, whether data collection is retrospective or prospective (or both), the start and end dates of the data to be collected, and whether the data were collected by the study authors or external to the study (e.g., collected as part of an administrative database). Data collection will be classified as retrospective if data were already available at the time of the protocol and as prospective if data will be collected during the study period. We will collect information to describe all time segments, including the start and end dates and the number of data points per segment. We will extract the model structure (if reported) or attempt to determine the model structure based on reported information (e.g., whether level change and/or slope change was modelled, whether the impact of the interruption was immediate or delayed, and how the interruption period was incorporated in the analysis). For statistical analysis methods, we will record the estimation method (e.g., ordinary least squares, restricted maximum likelihood), methods to deal with autocorrelation, seasonality, non-stationarity, and outliers; any adjustment for covariates; and use of control group and subgroup analyses.\n\nIn addition, we will record information related to the status of publication of the study results, as well as the journal name and date of publication for the protocol and all reports of the ITS results.\n\nFor all ITS outcomes addressing the primary research question(s), we will record the following details of the outcome, as presented in both the protocol and report(s) of the results: (a) the description of the outcome, (b) whether a higher value indicates benefit or harm, (c) whether the outcome was specified as a primary or secondary outcome, or neither; (d) the data type of the individual-level observations (e.g., dichotomous, continuous); and (e) the data type of the summary statistic used to aggregate the individual-level observations (e.g., count, percentage) within each period.\n\nFor all ITS results of the primary research question(s), we will record the effect measures reported (e.g. immediate level change, slope change), and (b) the available details about the results including: effect estimates, confidence intervals (along with level, e.g. 95%), exact P-values, statistical significance threshold (e.g. 5%), direction of the effect estimate (e.g. “favouring interruption group”).\n\n\nCorrespondence with study authors\n\nWe will contact the corresponding authors to seek unpublished information about their studies when there are (i) no report(s) of the results or (ii) missing or incompletely reported results for the primary research questions (as defined in “Study-level information”). We will contact the authors using the email address provided in the ITS study protocol or report(s) of the results. We will send up to three reminders to each author at a minimum of two weeks apart in the case of non-response. If the corresponding author does not respond, we will attempt to contact the other authors.\n\nOnce the study authors provide informed consent to participate in the study, we will provide them with an electronic survey via Qualtrics. The survey will seek information on whether data collection and analysis were completed, whether the study has been submitted to a journal, date of submission, publication and/or rejection, reasons for not submitting and potential reasons for rejection, and the name of the corresponding journal.\n\nFor each ITS study, we will ask if the authors are willing to share information pertaining to the outcomes and results relevant to the primary ITS research question(s). We will ask the authors to share the reasons for not reporting an outcome, reporting an outcome that was not specified in the protocol, or for inconsistencies in labelling the primary status of the outcome. For each result that was not reported or not fully reported, we will ask the authors whether the result was statistically significant (at the 5% significance threshold) and whether the effect estimate favors the interruption or the comparator group.\n\nThe data received from the authors will be stored in a secure location. In reporting results from our analyses, individual studies or their results will not be identifiable.\n\n\nStatistical analysis\n\nOnly ITS studies for which we have searched for report(s) of the results will be included in this analysis. Studies with ongoing recruitment or data collection, those confirmed to be abandoned, and those for which we have confirmed that the analysis has not been undertaken, will be excluded from our analysis.\n\nWe will calculate the percentage of protocols that do not have a report of ITS results and summarize the reasons why the results were not published. We define a ‘report of ITS results’ as a peer-reviewed report that includes results for any outcome pertaining to the primary ITS research question(s), as defined in “Study-level information”. We define ‘results’ as quantitative results (e.g. effect estimate, 95% confidence interval, P-value), or qualitative statements about the statistical significance, P-value or direction of the effect estimate. Where data are available, each result will be classified as statistically significant (P-value <0.05 or, if absent, the 95% confidence interval not including the null) or not statistically significant (P-value ≥0.05 or, if absent, 95% confidence interval including the null). The direction of the result will be classified as “favouring interruption group” (i.e. showing beneficial effects or reducing harm) or “favouring comparator group”.\n\nWe will undertake a multivariable Cox proportional hazards regression to determine whether a statistically significant effect estimate that favors the interruption group is associated with time to publication. Although statistical significance is not recommended for interpreting results, it is still widely used by researchers and journal editors to assess whether findings are potentially worth publishing17,27 and, therefore, may influence time to publication.28 Hazard ratios and 95% confidence intervals from the Cox regression analysis will be reported. Time to publication of results will be defined based on when the protocol is submitted relative to data collection. For studies where data collection was retrospective relative to the protocol submission, the time to publication will be from the protocol’s submission date to the date of publication of the results. If the date of protocol submission has not been reported, we will substitute it with the date of protocol publication. For studies in which the protocol submission occurs prior to or during data collection, the time to publication will be from the last date of the data collection period to the date of publication of the results. If there is more than one report of the ITS results, we will calculate the time to publication for each report. Protocols for which results for the primary research question(s) are not available will be censored on the date of the last search for results. The following potential confounding factors will be included as covariates in the model: type of funding (government, not-for-profit, industry, undisclosed, or no funding), presence of prospective registration, and timing of data collection relative to the date of the protocol (retrospective, prospective, or both). We will adjust for potential correlations arising from clustering of results within studies, which might arise from studies having multiple outcomes, multiple comparisons, or multiple results (Figure 2).\n\nStudies with at least one ITS report will be eligible for this analysis. For the primary research question(s), as defined in “Study-level information”, we will classify the study as having discrepancies in the reporting of outcomes if\n\n• Any outcome specified in the protocol was mentioned in the report of the results.\n\n• An outcome reported in the report of the results was not pre-specified in the protocol.\n\n• any outcome was inconsistently labelled (e.g. being described as’primary’ in the protocol but ‘secondary’ in the report of the results, or not being given a label in the protocol but being labelled as ‘primary’ or ‘secondary’ in the report of results). If an outcome is used in a power calculation, it will be considered the primary outcome.\n\nFor each effect estimate of each outcome, we classified the results using the approach proposed by Chan et al.29 as follows:\n\n• Fully reported – sufficient data is reported to include a result in a meta-analysis, that is, an effect estimate and a measure of precision (e.g., 95% confidence interval, standard error).\n\n• partially reported – insufficient data are reported to include a result in a meta-analysis (e.g., an effect estimate is reported without any measure of precision); or\n\n• qualitatively reported – only a statement about the statistical significance or the direction of the result (e.g. “there was no significant effect on road fatalities”), or only a P-value, is reported; or\n\n• unreported – an outcome is mentioned in the protocol but no result is reported.\n\nWe will calculate the percentage of ITS studies that have discrepancies in the reporting of outcomes, the percentage of results that are fully reported, partially reported, qualitatively reported, or unreported, and summarize the reasons provided by the study authors for any discrepancy in reporting outcomes or failure to report any result. We will conduct a multilevel multivariable logistic regression to determine whether a statistically significant effect estimate that favors the interruption group is associated with the full reporting of the results. We willfit two models, one unadjusted and one adjusted for the following potential confounders: type of funding (government, not-for-profit, industry, undisclosed, no funding) and outcome status (primary/secondary/unspecified).30 Both models will be adjusted for potential correlations arising from clustering of results within studies, which may arise from studies with multiple outcomes, multiple effect estimates for each outcome, and multiple comparisons (in series with more than two segments). In both models, calculated odds ratios and 95% confidence intervals will be reported.\n\nStudies with at least one ITS report will be eligible for this analysis. If there are multiple results reports for the primary research question(s), we will select the report with the most detailed methods for comparison with the protocol. When this decision is not clear, we will determine the selected report via discussion between two authors (PN and EK/ST/MJP/JEM). For the primary research question(s), as defined in “Study-level information”, we will compare the planned methods in the protocol and the primary report of the results to identify discrepancies in any aspect of the ITS methods, including the data collection process, model characteristics, and statistical analysis methods (see Table 1 for details). All discrepancies recorded will be reviewed by at least two statisticians (AF, EK, JEM, or ST) to judge whether the discrepancy was important; that is, whether the discrepancy could potentially change the result. A set of rules on what is considered an important discrepancy for each aspect of the methods will be determined via consensus among all the authors prior to data analysis. We will report the percentage of ITS studies that have any discrepancies and studies that have important discrepancies for each aspect of the methods. We will also summarize the rationales provided for the discrepancies, as reported by the study authors.\n\n\nDiscussion/conclusions\n\nSelective non-publication of studies and selective non-reporting of results can bias conclusions drawn in systematic reviews (with or without meta-analyses).18–20,31 Left-unaddressed, reporting biases in the ITS literature have the potential to lead to implementation of large-scale interventions that are at best, not effective, and at worst, harmful. Similar to other non-randomized studies, ITS literature is likely to be more prone to reporting biases than randomized trials because of a lack of mechanisms to encourage publication and reporting of all results, such as study registries, making registration a condition for publication, and guidelines for transparent reporting.23,24,32 Furthermore, the analysis of ITS designs involves making many decisions, such as choice of the model structure, unit of time for aggregating observations, statistical methods, whether and how to adjust for autocorrelation, and other potential confounders, which can yield varied results depending on the decisions chosen.4,15 Such multiplicity in analysis decisions provides an opportunity for study authors to report the most favorable results.\n\nTo our knowledge, this is the first study to systematically assess reporting biases among ITS studies across a range of topics and assess discrepancies in the reporting of methods between protocols and reports of their results. Knowledge of the prevalence of reporting biases will be useful for systematic reviewers and other stakeholders who rely on evidence from ITS studies and meta-analyses for decision-making. Furthermore, our results highlight the need for mechanisms to encourage complete reporting, such as the establishment of registries for non-randomized studies or planned analyses of existing datasets (e.g., administrative databases), along with incentives to register such studies and analyses. Moreover, based on our findings regarding the details of the methods most prone to discrepancies, future reporting checklists for ITS studies may incorporate recommendations for reporting these details.\n\nOur study has some limitations. First, it is difficult to identify ITS studies at their inception. Many studies evaluating publication bias and selective reporting of results have focused on randomized trials, where the trials were identified by ethics committees.33,34 We chose not to use ethics committees as a source for identifying ITS studies because ITS studies are sometimes undertaken without ethics approval being sought; thus, using this source would likely provide an incomplete sample of ITS studies. Instead, we will construct our sample from studies with a published protocol. However, using this sample may lead to underestimation of reporting biases, given that the presence of an a priori plan is associated with a higher quality of design35 and a lower likelihood of reporting biases.36 Second, it is possible that we may miss report(s) of the results that are published in gray literature or not made public.\n\nWe will seek ethical approval from the Monash University Human Research Ethics Committee before commencing the study.\n\nA consent form will be sent to all authors of the included ITS reports via email or the Qualtrics platform. Only data accompanied by signed consent forms will be included in the study.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nYoung JM, Stacey I, Dobbins TA, et al.: Association between tobacco plain packaging and Quitline calls: a population-based, interrupted time-series analysis. Med. J. Aust. 2014 Jan 20 [cited 2023 Aug 25]; 200(1): 29–32. Publisher Full Text\n\nHaber NA, Clarke-Deelder E, Salomon JA, et al.: Impact Evaluation of Coronavirus Disease 2019 Policy: A Guide to Common Design Issues. Am. J. Epidemiol. 2021 Nov 2; 190(11): 2474–2486. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKontopantelis E, Doran T, Springate DA, et al.: Regression based quasi-experimental approach when randomisation is not an option: interrupted time series analysis. BMJ. 2015 Jun 9 [cited 2023 Jan 28]; 350. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLopez Bernal J, Cummins S, Gasparrini A: Interrupted time series regression for the evaluation of public health interventions: a tutorial. Int. J. Epidemiol. 2017 Feb 1; 46(1): 348–355.\n\nRamsay CR, Matowe L, Grilli R, et al.: Interrupted time series designs in health technology assessment: Lessons from two systematic reviews of behavior change strategies. Int. J. Technol. Assess. Health Care. 2003; 19(4): 613–623. PubMed Abstract | Publisher Full Text\n\nEwusie JE, Soobiah C, Blondal E, et al.: Methods, Applications and Challenges in the Analysis of Interrupted Time Series Data: A Scoping Review. J. Multidiscip. Healthc. 2020 May 13; 13: 411–423. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHategeka C, Ruton H, Karamouzian M, et al.: Use of interrupted time series methods in the evaluation of health system quality improvement interventions: a methodological systematic review. BMJ Glob. Health. 2020 Oct; 5(10): e003567. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHudson J, Fielding S, Ramsay CR: Methodology and reporting characteristics of studies using interrupted time series design in healthcare. BMC Med. Res. Methodol. 2019 Jul 4; 19(1): 137. Publisher Full Text\n\nNavazi F, Yuan Y, Archer N: The effect of the Ontario stay-at-home order on Covid-19 third wave infections including vaccination considerations: An interrupted time series analysis. PLoS One. 2022 Apr 6; 17(4): e0265549. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThayer WM, Hasan MZ, Sankhla P, et al.: An interrupted time series analysis of the lockdown policies in India: a national-level analysis of COVID-19 incidence. Health Policy Plan. 2021 Jun 3; 36(5): 620–629. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMansfield KE, Mathur R, Tazare J, et al.: Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study. Lancet Digit. Health. 2021 Apr; 3(4): e217–e230. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPirkis J, John A, Shin S, et al.: Suicide trends in the early months of the COVID-19 pandemic: an interrupted time-series analysis of preliminary data from 21 countries. Lancet Psychiatry. 2021 Jul; 8(7): 579–588. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShah SA, Brophy S, Kennedy J, et al.: Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people. eClinicalMedicine. 2022 Jul 1 [cited 2023 Jun 20]; 49.\n\nLangan D, Higgins JPT, Jackson D, et al.: A comparison of heterogeneity variance estimators in simulated random-effects meta-analyses. Res. Synth. Methods. 2019 Mar 1; 10(1): 83–98. PubMed Abstract | Publisher Full Text\n\nTurner SL, Karahalios A, Forbes AB, et al.: Comparison of six statistical methods for interrupted time series studies: empirical evaluation of 190 published series. BMC Med. Res. Methodol. 2021 Jun 26; 21(1): 134.\n\nDeeks JJ, Higgins JPT, Altman DG: Chapter 10: Analysing data and undertaking meta-analyses. Cochrane Handbook for Systematic Reviews of Interventions. 6.3. Cochrane Collaboration; 2022 [cited 2023 Feb 21].\n\nSimmons JP, Nelson LD, Simonsohn U: False-Positive Psychology: Undisclosed Flexibility in Data Collection and Analysis Allows Presenting Anything as Significant. Psychol. Sci. 2011 Nov 1; 22(11): 1359–1366. Publisher Full Text\n\nKicinski M: How does under-reporting of negative and inconclusive results affect the false-positive rate in meta-analysis? A simulation study. BMJ Open. 2014 Aug 1; 4(8): e004831. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSmyth RMD, Kirkham JJ, Jacoby A, et al.: Frequency and reasons for outcome reporting bias in clinical trials: interviews with trialists. BMJ. 2011 Jan 6; 342: c7153. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSutton AJ, Duval SJ, Tweedie RL, et al.: Empirical assessment of effect of publication bias on meta-analyses. BMJ. 2000 Jun 10; 320(7249): 1574–1577. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChan AW, Pello A, Kitchen J, et al.: Association of Trial Registration With Reporting of Primary Outcomes in Protocols and Publications. JAMA. 2017 Nov 7; 318(17): 1709–1711. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGopal AD, Wallach JD, Aminawung JA, et al.: Adherence to the International Committee of Medical Journal Editors’ (ICMJE) prospective registration policy and implications for outcome integrity: a cross-sectional analysis of trials published in high-impact specialty society journals. Trials. 2018 Aug 23; 19: 448. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQuintana DS: From pre-registration to publication: a non-technical primer for conducting a meta-analysis to synthesize correlational data. Front. Psychol. 2015 [cited 2023 Jun 21]; 6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTanaka S, Tanaka S, Kawakami K: Methodological issues in observational studies and non-randomized controlled trials in oncology in the era of big data. Jpn. J. Clin. Oncol. 2015 Apr; 45(4): 323–327. PubMed Abstract | Publisher Full Text\n\nNguyen PY, McKenzie JE, Turner SL, et al.: Development of a search filter to retrieve reports of interrupted time series studies from MEDLINE and PubMed. medRxiv. 2023 [cited 2023 Sep 27]; 2023.09.14.23295594.\n\nHarris PA, Taylor R, Thielke R, et al.: Research electronic data capture (REDCap)-A metadata-driven methodology and workflow process for providing translational research informatics support. J. Biomed. Inform. 2009 Apr; 42(2): 377–381. Publisher Full Text\n\nSterne JAC, Cox DR, Smith GD: Sifting the evidence—what’s wrong with significance tests? Another comment on the role of statistical methods. BMJ. 2001 Jan 27; 322(7280): 226–231. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHopewell S, Loudon K, Clarke MJ, et al.: Publication bias in clinical trials due to statistical significance or direction of trial results. Cochrane Database Syst. Rev. 2009 Jan 21; 2009(1): MR000006. PubMed Abstract | Publisher Full Text\n\nChan AW, Hróbjartsson A, Haahr MT, et al.: Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles. JAMA. 2004 May 26; 291(20): 2457–2465. Publisher Full Text\n\nLi G, Abbade LPF, Nwosu I, et al.: A systematic review of comparisons between protocols or registrations and full reports in primary biomedical research. BMC Med. Res. Methodol. 2018 Jan 11; 18(1): 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPage MJ, Higgins JP, Sterne JA: Assessing risk of bias due to missing results in a synthesis. Cochrane Handbook for Systematic Reviews of Interventions. John Wiley & Sons, Ltd; 2019 [cited 2023 Aug 25]; pp. 349–374. Publisher Full Text\n\nInternational Committee of Medical Journal Editors: Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly Work in Medical Journals. Updated.Jan 2024.\n\nDwan K, Gamble C, Williamson PR, et al.: Systematic review of the empirical evidence of study publication bias and outcome reporting bias - an updated review. PLoS One. 2013; 8(7): e66844. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDwan K, Altman DG, Clarke M, et al.: Evidence for the selective reporting of analyses and discrepancies in clinical trials: a systematic review of cohort studies of clinical trials. PLoS Med. 2014 Jun; 11(6): e1001666. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSideri S, Papageorgiou SN, Eliades T: Registration in the international prospective register of systematic reviews (PROSPERO) of systematic review protocols was associated with increased review quality. J. Clin. Epidemiol. 2018 Aug 100; 100: 103–110. Publisher Full Text\n\nChan AW, Hróbjartsson A: Promoting public access to clinical trial protocols: challenges and recommendations. Trials. 2018 Feb 17; 19(1): 116. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "289038",
"date": "19 Jun 2024",
"name": "Jos Verbeek",
"expertise": [
"Reviewer Expertise environmental and occupational health",
"systematic reviews"
],
"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 protocol for a study of a cohort of protocols for interrupted timeseries studies (ITS) to evaluate if there is outcome reporting bias in the final study reports or whether there is publication bias due to the study report not being published.\nGeneral comment: I agree with the authors that ITS studies are a valuable design to evaluate higher level policy or legal interventions where experimental studies are difficult to perform because of the interventions are applied to a large group of persons. The main prerequisite for an ITS study is that the outcome data are routinely collected. Therefore, I wouldn’t immediately consider outcome reporting bias as one of the biggest threats to their validity. The authors don’t have much choice for the outcome, either it is available or not. Nevertheless, it might be good to evaluate this.\nMore specific comments:\nI was a bit confused if this was now about publication bias in systematic reviews (SR) or about outcome reporting in studies. The authors write: ‘However, the suppression of ITS studies or results within these studies (known as reporting bias) has the potential to bias conclusions drawn in such systematic reviews, with potential consequences for healthcare decision-making. Therefore, we aim to determine whether there is evidence of reporting bias among ITS studies.’ The suppression of ITS studies must refer to SRs but as such it sounds as if the authors of the SR would actively not include studies based on their results. I think this does not make sense. I think it would help if it were clear that both publication bias and outcome reporting bias will be studied from the perspective of the study authors. Outcome reporting bias can also occur in a SR but that will not be studied here. The final objective is of course to prevent distortion of the results in the evidence base in a SR but that will not be studied here.\n\nI think it would be helpful to better define reporting bias and how it will be studied at the very start of the protocol. Now the authors write: ‘A key factor underpinning the validity of the findings from systematic reviews is the extent to which the included studies (and their results) are representative of missing studies, a concept known as reporting bias.’ I think this is not totally correct and is much better described later on where they say: ‘Reporting bias can arise when there is suppression of entire studies (known as publication bias) or results within studies that are unfavorable to the study hypotheses (known as selective reporting bias) due to the nature of the results themselves (i.e., based on their direction, magnitude, or P-value)\n\nI think the main issue with this protocol is that there will be no ITS-protocols. It is like the authors write: ‘Unlike randomized trials, where prospective registration is required by ethics committees and journals,21,22 and many trial registries exist, such requirements and registries do not exist for ITS studies.’ This sentence undermines the whole study. If there are no protocols, there is no study or it will be an open-door result that there are no protocols. Can the authors please confirm that they know that there is a sufficient number of protocols available to do this study? It is laudable that the authors define their data clearly. However, I think this one on the direction of the effect estimate (e.g. “favouring interruption group”) is not correct. Later the write similarly: The direction of the result will be classified as “favouring interruption group” (i.e. showing beneficial effects or reducing harm) or “favouring comparator group”. For most ITS there is no comparison group and that is the very reason that the ITS design was chosen. The direction should be defined as ‘favouring the intervention time-period’ of ‘favouring the pre-intervention time-period’. Also when there is a comparison group, it is usual to take the difference in the outcomes between the intervention and the comparison group and analyze if the effect size is different between the pre and post intervention period. If I understand correctly what the authors want to do, they will assemble a cohort of protocols and the protocol will be the study unit. Where it is said: ‘Only ITS studies for which we have searched for report(s) of the results will be included in this analysis.’, I assume that is meant ‘Only ITS protocols for which.. I got confused by the following statements about how to classify the study as having discrepancies in the reporting of outcomes if\n\nAny outcome specified in the protocol was mentioned in the report of the results. An outcome reported in the report of the results was not pre-specified in the protocol.\n\nI think the first one does not show a discrepancy and should be deleted.\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": [
{
"c_id": "12658",
"date": "04 Nov 2024",
"name": "Phoebe Nguyen",
"role": "Author Response",
"response": "We would like to thank the reviewer for the thoughtful and helpful feedback. Please find our responses to each comment below. FEEDBACK: This is a protocol for a study of a cohort of protocols for interrupted timeseries studies (ITS) to evaluate if there is outcome reporting bias in the final study reports or whether there is publication bias due to the study report not being published. General comment: I agree with the authors that ITS studies are a valuable design to evaluate higher level policy or legal interventions where experimental studies are difficult to perform because of the interventions are applied to a large group of persons. The main prerequisite for an ITS study is that the outcome data are routinely collected. Therefore, I wouldn’t immediately consider outcome reporting bias as one of the biggest threats to their validity. The authors don’t have much choice for the outcome, either it is available or not. Nevertheless, it might be good to evaluate this. RESPONSE: We agree with the reviewer that many ITS studies use routinely collected data to examine the impacts of the interruption. However, in our methodological reviews examining design characteristics of ITS studies, we have found this is not always the case (Korevaar et al, 2022; Turner et al, 2020). Furthermore, even where routinely collected data is used, there may be multiple outcomes available that could be used to assess the impact of the interruption, providing opportunities for selective reporting of outcomes. For example, in ITS studies examining the effects of antimicrobial stewardship programs to reduce inappropriate antimicrobial prescribing, routine data is collected on prescribing of all antimicrobial agents (e.g. amikacin, azithromycin, cefepime, ceftazidime, ceftriaxone), of which some, or all, could be used to evaluate the impact of the intervention. FEEDBACK: I was a bit confused if this was now about publication bias in systematic reviews (SR) or about outcome reporting in studies. The authors write: ‘However, the suppression of ITS studies or results within these studies (known as reporting bias) has the potential to bias conclusions drawn in such systematic reviews, with potential consequences for healthcare decision-making. Therefore, we aim to determine whether there is evidence of reporting bias among ITS studies.’ The suppression of ITS studies must refer to SRs but as such it sounds as if the authors of the SR would actively not include studies based on their results. I think this does not make sense. I think it would help if it were clear that both publication bias and outcome reporting bias will be studied from the perspective of the study authors. Outcome reporting bias can also occur in a SR but that will not be studied here. The final objective is of course to prevent distortion of the results in the evidence base in a SR but that will not be studied here. RESPONSE: We have amended the background of the abstract to make it clear that our focus is on reporting bias of individual ITS studies. The text now reads: “Interrupted time-series (ITS) studies are commonly used to examine the effects of interventions targeted at populations. Suppression of ITS studies or results within these studies, known as reporting bias, has the potential to bias the evidence-base on a particular topic, with potential consequences for healthcare decision-making. Therefore, we aim to determine whether there is evidence of reporting bias among ITS studies.” FEEDBACK: I think it would be helpful to better define reporting bias and how it will be studied at the very start of the protocol. Now the authors write: ‘A key factor underpinning the validity of the findings from systematic reviews is the extent to which the included studies (and their results) are representative of missing studies, a concept known as reporting bias.’ I think this is not totally correct and is much better described later on where they say: ‘Reporting bias can arise when there is suppression of entire studies (known as publication bias) or results within studies that are unfavorable to the study hypotheses (known as selective reporting bias) due to the nature of the results themselves (i.e., based on their direction, magnitude, or P-value) RESPONSE: We have amended the text as follows: “Systematic reviews may be undertaken to collate and synthesize evidence on the effects of interventions. In reviews that examine the effects of policy interventions, ITS studies are likely to be eligible because evidence from randomized trials may be limited or unavailable. A key factor underpinning the validity of the findings from systematic reviews is the extent of reporting bias in the evidence-base. Reporting bias can arise when there is suppression of entire studies […]”. FEEDBACK: I think the main issue with this protocol is that there will be no ITS-protocols. It is like the authors write: ‘Unlike randomized trials, where prospective registration is required by ethics committees and journals,21,22 and many trial registries exist, such requirements and registries do not exist for ITS studies.’ This sentence undermines the whole study. If there are no protocols, there is no study or it will be an open-door result that there are no protocols. Can the authors please confirm that they know that there is a sufficient number of protocols available to do this study? RESPONSE: Since submitting the protocol, we have completed the search and eligibility screening from which we have identified 158 protocols for ITS studies. FEEDBACK: It is laudable that the authors define their data clearly. However, I think this one on the direction of the effect estimate (e.g. “favouring interruption group”) is not correct. Later the write similarly: The direction of the result will be classified as “favouring interruption group” (i.e. showing beneficial effects or reducing harm) or “favouring comparator group”. For most ITS there is no comparison group and that is the very reason that the ITS design was chosen. The direction should be defined as ‘favouring the intervention time-period’ of ‘favouring the pre-intervention time-period’. Also when there is a comparison group, it is usual to take the difference in the outcomes between the intervention and the comparison group and analyze if the effect size is different between the pre and post intervention period. RESPONSE: We have used the term ‘group’ to refer to interventions or exposures that occur in different time periods (segments). This is similar to the use of ‘group’ in controlled trials, except that in trials, groups are formed by assigning units, whereas in ITS studies, they are defined by time. To make this clearer, we have added the following sentence in Section 2.1: “Note that we use the term ‘group’ to refer to interventions or exposures that occur in different time periods (segments).” FEEDBACK: If I understand correctly what the authors want to do, they will assemble a cohort of protocols and the protocol will be the study unit. Where it is said: ‘Only ITS studies for which we have searched for report(s) of the results will be included in this analysis.’, I assume that is meant ‘Only ITS protocols for which.. RESPONSE: The reviewer has understood correctly. We have amended the sentence to “Only ITS protocols for which…”. FEEDBACK: I got confused by the following statements about how to classify the study as having discrepancies in the reporting of outcomes if Any outcome specified in the protocol was mentioned in the report of the results. An outcome reported in the report of the results was not pre-specified in the protocol. I think the first one does not show a discrepancy and should be deleted. RESPONSE: We have amended the sentence to “Any outcome specified in the protocol that was not mentioned in the report of the results”."
}
]
},
{
"id": "268184",
"date": "10 Sep 2024",
"name": "Qian Yu",
"expertise": [
"Reviewer Expertise Clinical pharmacy"
],
"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 recommend the authors to address the aforementioned improvements. The study is well-positioned to contribute valuable insights into reporting biases in ITS studies, which is pivotal for enhancing the reliability of systematic reviews in healthcare research. 1. Explain why Cox proportional hazards regression and multivariable logistic regression were chosen as the main analysis tools. 2. Add cases of interrupted time series studies from different countries or regions to the background section, especially those related to reporting bias. This will help readers understand the global and prevalent nature of the issue. Compare studies internationally to analyze the potential causes and consequences of reporting bias across different countries or cultural backgrounds. 3. The study mentions seeking ethical approval and consent forms, but does not detail the procedures for protecting participant confidentiality and data security during the survey and data collection phases. Clarifying these aspects would strengthen the ethical considerations section.\n\nIs the rationale for, and objectives of, the study clearly described? Yes\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "12659",
"date": "04 Nov 2024",
"name": "Phoebe Nguyen",
"role": "Author Response",
"response": "We would like to thank the reviewer for the thoughtful and helpful feedback. Please find our responses to each comment below. FEEDBACK: I recommend the authors to address the aforementioned improvements. The study is well-positioned to contribute valuable insights into reporting biases in ITS studies, which is pivotal for enhancing the reliability of systematic reviews in healthcare research. 1. Explain why Cox proportional hazards regression and multivariable logistic regression were chosen as the main analysis tools. RESPONSE: Under objective 1, we aim to investigate the impact of the direction and statistical significance of results on time to publication. Time to publication is time-to-event data, which means it incorporates two aspects: (i) whether the study was published or not, and if it was, (ii) the time until publication. Statistical methods that assume that the outcome is continuous can introduce bias; hence we are using a statistical method that was developed for time-to-event data – Cox proportional hazards regression. Under objective 2, we aim to investigate the impact of the direction and statistical significance of results on how completely the result is reported. The outcome ‘reporting status of the result’ is a binary outcome (fully reported or not), and therefore logistic regression (with a binomial distribution and a logit link function) is an appropriate statistical method for this outcome type. We are using multivariable regression because we wish to adjust for potential confounding variables. FEEDBACK: Add cases of interrupted time series studies from different countries or regions to the background section, especially those related to reporting bias. This will help readers understand the global and prevalent nature of the issue. Compare studies internationally to analyze the potential causes and consequences of reporting bias across different countries or cultural backgrounds. RESPONSE: The ITS studies we cite in the Introduction were set in multiple countries (#9-12): Canada (#9), India (#10) and UK (#11); one country investigated 21 countries across multiple regions and income levels (#12). We have also added the following sentence to the Introduction which reflects the findings from methods reviews examining the characteristics of ITS studies: “The design has primarily been used in high-income countries, and to a more limited extent in low- and middle-income countries.” Regarding the reviewer’s suggestion to provide information in the Introduction on the prevalence of reporting bias in ITS studies, and on the potential causes and consequences of reporting bias across different countries and cultural backgrounds, we are unaware of any studies that have examined reporting bias in the ITS literature; hence the reason for undertaking the present study. FEEDBACK: The study mentions seeking ethical approval and consent forms, but does not detail the procedures for protecting participant confidentiality and data security during the survey and data collection phases. Clarifying these aspects would strengthen the ethical considerations section. RESPONSE: We now provide more information about confidentiality and data security under the ‘Ethical considerations’ Section: “We will seek ethics approval from the Monash University Human Research Ethics Committee before contacting the study authors to clarify and seek missing information from their publications. A consent form will be sent to authors of the included ITS reports via email or via a Monash University approved survey provider (Qualtrics). Only data accompanied by signed consent forms will be included in the study. Findings from the quantitative analysis will be reported in aggregate to maintain study authors’ confidentiality. Data will be stored on a Monash University secure server.” We have also clarified that only data that is publicly available from the ITS protocols and their associated reports will be made available in the ‘Data availability’ Section: “Data that is extracted from the published ITS protocols and their associated reports will be deposited in a free-access data repository with a CC-BY license allowing reuse with attribution, and assigned a digital object identifier (DOI).”"
}
]
}
] | 1
|
https://f1000research.com/articles/13-153
|
https://f1000research.com/articles/13-894/v1
|
06 Aug 24
|
{
"type": "Brief Report",
"title": "Identification of heart rate dynamics during treadmill and cycle ergometer exercise: the role of model zeros and dead time",
"authors": [
"Kenneth J. Hunt",
"Hanjie Wang",
"Hanjie Wang"
],
"abstract": "Background The response of heart rate to changes in exercise intensity is comprised of several dynamic modes with differing magnitudes and temporal characteristics. Investigations of empirical identification of dynamic models of heart rate showed that second-order models gave substantially and significantly better model fidelity compared to the first order case. In the present work, we aimed to reanalyse data from previous studies to more closely consider the effect of including a zero and a pure delay in the model.\n\nMethods This is a retrospective analysis of 22 treadmill (TM) and 54 cycle ergometer (CE) data sets from a total of 38 healthy participants. A linear, time-invariant plant model structure with up to two poles, a zero and a dead time is considered. Empirical estimation of the free parameters was performed using least-squares optimisation. The primary outcome measure is model fit, which is a normalised root-mean-square model error.\n\nResults A model comprising parallel connection of two first-order transfer functions, one with a dead time and one without, was found to give the highest fit (56.7 % for TM, 54.3 % for CE), whereby the non-delayed component appeared to merely capture initial transients in the data and the part with dead time likely represented the true dynamic response of heart rate to the excitation. In comparison, a simple first-order model without dead time gave substantially lower fit than the parallel model (50.2 % for TM, 47.9 % for CE).\n\nConclusions This preliminary analysis points to a linear first-order system with dead time as being an appropriate model for heart rate response to exercise using treadmill and cycle ergometer modalities. In order to avoid biased estimates, it is vitally important that, prior to parameter estimation and validation, careful attention is paid to data preprocessing in order to eliminate transients and trends.",
"keywords": [
"heart rate dynamics",
"system identification",
"treadmill exercise",
"cycle ergometer exercise"
],
"content": "1. Introduction\n\nIt has been proposed that heart rate response to changes in exercise intensity comprises three main phases1,2: an immediate, relatively small and fast Phase I; a slower, delayed and larger Phase II; and, if the exercise intensity exceeds the anaerobic threshold, a later and very slow Phase III drift.\n\nThis observation led to the investigation of empirical identification of dynamic models of heart rate using first- and second-order transfer functions for treadmill (TM)3 and cycle ergometer (CE)4 exercise. The second-order case was anticipated to capture Phase I and II response modes; but, since the models were intended to be used for analytical design of feedback controllers for heart rate, where integral action would cancel very slow drift, Phase III was not considered; in addition, to simplify feedback design, dead time was neglected.\n\nThus, in both of the preceding investigations of heart rate dynamics3,4 the dynamic response of heart rate was modelled as nominal linear transfer functions Po(s) of first (P1) and second (P2) order:\n\nIt was found that second-order models gave substantially and significantly better model fidelity compared to the first order case (TM,3 CE4) and that feedback control of heart rate was more accurate when based on second-order models (TM,5 CE4).\n\nBut the classical Phase I - Phase II model of heart rate response1,2 comprises the parallel connection of two first-order models, i.e. the sum of a first-order transfer function of the form P1 above and a P1 with pure delay. Theoretically, this would lead to a second-order model with two poles, but also—when dead time is neglected—with a single zero. The effect of this (theoretical) zero was not reported in the previous studies3,4 as it was found not to lead to any difference in empirical model fit, presumably due to overfitting. Furthermore, since the classical sources propose the addition of a dead time to one of the modes to capture the slightly later onset of the Phase II component, the inclusion of a pure delay warrants further attention.\n\nThe present work therefore aimed to perform a retrospective analysis of the previous investigations of heart rate dynamics during treadmill3 and cycle ergometer4 exercise to more closely consider the effect of including a zero and a dead time in the model. The respective datasets are available on the OLOS repository.6,7\n\n\n2. Methods\n\nFull details of experimental procedures employed for data collection in the preceding treadmill and cycle ergometer investigations can be found in the respective publications.3,4 Essential elements of the protocols are summarised in this Brief Report.\n\nFor both exercise modalities, healthy, able-bodied participants exercised at moderate-to-vigorous intensity: in the treadmill analysis3 there were 11 participants; for the cycle ergometer4 there were 27. A similar pseudo-random binary sequence (PRBS) input signal was employed in both cases to excite relevant modes of heart rate response dynamics. All participants performed two identical open-loop identification tests to facilitate counterbalanced cross-validation of model parameter estimates: consequently, there were 22 TM data sets and 54 CE data sets. All of these data sets were included in the present retrospective analysis.\n\nTo aid the following Discussion (Sec. 4), all existing heart rate measurements that were included in the parameter estimation and validation procedures are illustrated (Figure 1).\n\nIn each plot, thin lines are the individual measurements (22 for TM, 54 for CE); the thick red lines are averages of the individual measurements. Data are plotted as deviations △ HR around mean heart rate levels. (a) Treadmill, (b) Cycle Ergometer.\n\nIn the present work, we consider a linear, time-invariant (LTI) plant model structure with up to two poles, a zero and a dead time, that maps an input signal u to the output y, namely\n\nThe generic plant output signal y corresponds to heart rate [beats/min, bpm] while the input u depends on the exercise modality: for the treadmill, it is speed [m/s]; for the cycle ergometer, it is work rate [W]. As noted above, the input for both modalities took the form of a PRBS signal.\n\nEmpirical parameter estimation was performed using the Matlab System Identification Toolbox (The MathWorks, Inc., USA), wherefore, in the table (Table 1), we have adopted model names corresponding to the terminology used in the toolbox. In general, models of the form Eq. (2) are referred to in the toolbox as “process models”.\n\nEstimation of the free model parameters—k, the τ’s, Tz and Td in Eq. (2), constrained for the different model structures as indicated in Table 1—was done with the Matlab procest function using least-squares optimisation with regularly sampled time-domain data.8 To focus the search algorithm, model parameters were constrained to lie in physiologically plausible ranges. As in our previous work3,4 separate models were identified for each individual data set and counterbalanced cross-validation was employed by pairing the two measurements for each participant.\n\nThe primary outcome measure is model fit, which is a normalised root-mean-square model error (NRMSE):\n\n\n3. Results\n\nGoodness-of-fit values for the seven model structures and two exercise modalities are summarised in Table 2; the estimated model parameters are also tabulated (Table 3).\n\n* For the P1∥P1D model structure, parameters are shown separately for the P1 (second-bottom row) and P1D (bottom row) components: k and τ1 correspond respectively to kp1 and τp1, or kp2 and τp2, in the bottom row of Table 1.\n\n\n4. Discussion\n\nGoodness-of-fit outcomes for the treadmill and cycle ergometer followed a similar pattern. There was a substantial improvement in fit for P1D vs. P1, indicating the clear presence of dead time in heart rate response; Td for P1D was similar for TM and CE at 13.1 s and 13.8 s, respectively (Table 3).\n\nModel fit for P2, P2D and P2Z was similar to P1D, while P2ZD showed a further slight improvement. It has to be remarked, however, that estimated Tz values for individual models varied widely on the range -15 s to 100 s, thus displaying in part negative-phase behaviour (i.e. Tz<0). Furthermore, fit for P2Z was slightly lower than for P1D, P2 and P2D. Taken together, these observations point to a degree of overfitting when a plant zero is included.\n\nHaving excluded further consideration of models with a zero, we note a further substantial increase in fit for the parallel P1∥P1D model structure when compared to P1D, P2 and P2D. A critical observation in this regard is that the P1 parameters in the P1∥P1D structure displayed very small gains and very large time constants when compared to the parallel-models’ P1D parameters (Table 3): for the TM, the gains were 7.0 bpm/(m/s) and 20.2 bpm/(m/s), (P1 vs. P1D), and the time constants 141.5 s vs. 34.3 s; for the CE, gains were 0.09 bpm/W vs. 0.35 bpm/W and time constants 180.7 s vs. 37.9 s.\n\nA likely explanation for this apparent anomaly can be gleaned by perusal of the heart rate measurements (Figure 1). It can be seen that there is a small yet clearly discernible drift in heart rate during the first few minutes of the responses, with the duration of drift in line with the observed P1 time constants 141.5 s (TM, Figure 1a) and 180.7 s (CE, Figure 1b). It is therefore plausible that the P1 part of the P1∥P1D model merely reflects the initial transient, while the P1D part represents the true dynamic response of heart rate to the excitation. Care should therefore be taken in future investigations to exclude initial transients and slow trends prior to parameter estimation and validation.\n\nThe gains and time constants are seen to be somewhat lower for the P1D part of the P1∥P1D model than for the P1D-only model (gains 20.2 bpm/(m/s) vs. 25.0 bpm/(m/s) for TM, 0.35 bpm/W vs. 0.40 bpm/W for CE; time constants 34.3 s vs. 47.7 s for TM, 37.9 s vs. 45.9 s for CE; Table 3), and the dead times somewhat higher (17.9 s vs. 13.1 s for TM, 17.1 s vs. 13.8 s for CE). These differences are likely due to model bias introduced in the P1D-only model as a consequence of the initial drift in heart rate, as discussed above.\n\nAs noted in previous reports3,4 second-order models of the form P2 gave substantially and significantly better fidelity than first-order models P1 (cf. Table 2). However, the identification here of a substantial dead time, coupled with the observed superiority of the P1D part of the parallel P1∥P1D model (following elimination of heart rate drift), suggests that the second time constant in the P2 model may simply have partially absorbed the neglected time delay rather than having modelled any underlying dynamic mode in the heart rate response.\n\nA final observation is that the time constants for the TM and CE, when compared for all seven model structures, are in strikingly close agreement (Table 3). This is in line with a previous comparison of heart rate dynamics between the TM and CE modalities that showed no significant difference in the time constant of heart rate response.9\n\nDue to the retrospective nature of this investigation—that used existing data sets—the results and conclusions are considered to be provisional, but they do provide insights for the design of future studies: to avoid the confounding effect of initial transients, the plant input test signal should be designed to ensure that a physiological steady state has been reached in advance of the data evaluation period; a formal, statistical study design should be employed for comparison of the different model structures - the results of the present work provide effect-size estimates for statistical power and sample size calculations.\n\n\n5. Conclusions\n\nThis preliminary analysis points to the P1D structure—that is to say, a linear first-order system with dead time—as being an appropriate model for heart rate response to exercise using treadmill and cycle ergometer modalities. In order to avoid biased estimates, it is vitally important that, prior to parameter estimation and validation, careful attention is paid to data preprocessing in order to eliminate transients and trends.\n\nThe study that generated both the treadmill and cycle ergometer datasets was performed in accordance with the Declaration of Helsinki; the study was reviewed and approved by the Ethics Committee of the Swiss Canton of Bern (Ref. 2019-02184; approval date 16 January 2020). Participants provided written, informed consent prior to inclusion in the study.\n\n\nAuthors’ contributions\n\nBoth authors made substantial contributions to the conception and design of the study; HW did the treadmill data acquisition; KH and HW performed the data analysis; both authors contributed to the interpretation of the data. KH drafted the manuscript; HW reviewed it critically for important intellectual content. Both authors read and approved the final manuscript.",
"appendix": "Data availability\n\nThe datasets analysed in this research are available in the OLOS repository as follows:\n\nIdentification of heart rate dynamics during treadmill exercise: comparison of first- and second-order models - Treadmill dataset, https://doi.org/10.34914/olos:bivq3dcebff5dfrqtbf3v5y7si. 6\n\nHeart rate dynamics identification and control in cycle ergometer exercise: Comparison of first- and second-order performance --Cycle ergometer dataset, https://doi.org/10.34914/olos:xtyv7akiu5bzdba3oemrarg4ru. 7\n\nPlease click on the link, then click on the “Files” tab at the bottom right of the screen to access the data.\n\nData is available under the terms of the Creative Commons Attribution 4.0 International license.\n\n\nAcknowledgements\n\nAlexander Spörri (Bern University of Applied Sciences) did the cycle ergometer data acquisition.\n\n\nReferences\n\nWhipp BJ, Ward SA, Lamarra N, et al.: Parameters of ventilatory and gas exchange dynamics during exercise. J. Appl. Physiol. 1982; 52(6): 1506–1513. Publisher Full Text\n\nBearden SE, Moffat RJ: VO2 and heart rate kinetics in cycling: transitions from an elevated baseline. J. Appl. Physiol. 2001; 90(6): 2081–2087. PubMed Abstract | Publisher Full Text\n\nWang H, Hunt KJ: Identification of heart rate dynamics during treadmill exercise: comparison of first- and second-order models. Biomed. Eng. Online. 2021; 20(37): 10–37. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpörri AH, Wang H, Hunt KJ: Heart rate dynamics identification and control in cycle ergometer exercise: comparison of first- and second-order performance. Front. Control Eng. 2022; 3: 894180. Publisher Full Text\n\nWang H, Hunt KJ: Feedback control of heart rate during treadmill exercise based on a two-phase response model. PLoS One. 2023; 18(10): e0292310. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang H, Hunt KJ: Identification of heart rate dynamics during treadmill exercise: comparison of first- and second-order models. [Dataset]. OLOS Repository. 2023. Publisher Full Text\n\nSpörri AH, Wang H, Hunt KJ: Heart rate dynamics identification and control in cycle ergometer exercise: comparison of first- and second-order performance. [Dataset]. OLOS Repository. 2023. Publisher Full Text\n\nLjung L: System Identification: theory for the user. 2nd ed.Upper Saddle River, New Jersey, USA: Prentice Hall; 1998.\n\nHunt KJ, Grunder R, Zahnd A: Identification and comparison of heart-rate dynamics during cycle ergometer and treadmill exercise. PLoS One. 2019; 14(8): e0220826. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "317159",
"date": "27 Aug 2024",
"name": "Przemysław Seweryn Kasiak",
"expertise": [
"Reviewer Expertise Sports Cardiology"
],
"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\nFirstly, I would like to thank for inviting me as a Referee of this study. This research touches an important topic of heart rate during exercise and provide useful piece of knowledge for clinicians and sport practitioners. I am providing my comments for the Authors below.\nMajor issues:\nI suggest more precise description of the rationale for this study from clinical and physiological perspective. Perhaps, an additional paragraph in the introduction would be welcome. Similarly, there is a lack of information about practical applications of this study in the discussion.\n\nMinor issues:\nI suggest providing a brief description of the study population in the abstract. If the Authors will meet the word limit, I strongly recommend enhancing the information about study group (their demographics, fitness level etc.) and testing protocols.\n\nDid the Authors evaluate sample size to ensure credibility of their analysis and conclusions? There are only 38 participants in this study.\n\nIn summary, this study is interesting. Further analysis of the preliminary report would be helpful for deep understanding of heart rate response to exercises.\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? Partly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12703",
"date": "01 Nov 2024",
"name": "Kenneth Hunt",
"role": "Author Response",
"response": "Dear Reviewers Many thanks for your detailed and constructive comments on our manuscript. We are pleased to provide a point-by-point response below. Changes to the manuscript have been implemented as noted below and submitted using “track changes” in the revised manuscript. With best wishes. Yours faithfully The authors Reviewer #1 Report and Response: Przemysław Seweryn Kasiak Firstly, I would like to thank for inviting me as a Referee of this study. This research touches an important topic of heart rate during exercise and provide useful piece of knowledge for clinicians and sport practitioners. I am providing my comments for the Authors below. RESPONSE: Dziękuję bardzo—and thank you very much for your helpful comments, especially for your observation of relevance for clinicians and sport practitioners. Major issues: I suggest more precise description of the rationale for this study from clinical and physiological perspective. Perhaps, an additional paragraph in the introduction would be welcome. Similarly, there is a lack of information about practical applications of this study in the discussion. RESPONSE: Thank you for these suggestions. We agree it is very useful to provide more information regarding the clinical and physiological perspectives, and practical applications. To address both of these points, we have added the following paragraph at the start of the Introduction: “Heart rate is an easy-to-measure physiological variable that can be used to characterise the intensity of exercise, both quantitatively and qualitatively using categories such as light, moderate and vigorous [10]. The ability to regulate heart rate during exercise using feedback control would therefore allow accurate prescription of training regimes in both clinical and non-clinical settings. Since feedback controllers require a model of the dynamic response of heart rate during exercise, it is important to first consider the fidelity of different model structures.” New reference [10]: 10. Riebe D, Ehrman JK, Liguori G, Magal M, editors. ACSM’s guidelines for exercise testing and prescription. 10th ed. Philadelphia: Wolters Kluwer; 2018. Minor issues: I suggest providing a brief description of the study population in the abstract. RESPONSE: Regrettably, the Abstract already has 298 words, with a limit of 300 words. But we have provided more detailed information on the study population in the main text as noted below. If the Authors will meet the word limit, I strongly recommend enhancing the information about study group (their demographics, fitness level etc.) and testing protocols. RESPONSE: Thank you for this suggestion. As mentioned in the text, this is a retrospective analysis of data from two previously-published studies. We pointed out that full information regarding the study groups and testing protocols can be found in the corresponding citations, viz. references [3] and [4], as follows: “Full details of experimental procedures employed for data collection in the preceding treadmill and cycle ergometer investigations can be found in the respective publications. 3 , 4 Essential elements of the protocols are summarised in this Brief Report.” Nevertheless, we do agree it would be helpful to the reader to have more information in the current article, for which reason we have added more details to the Methods, as follows: “For both exercise modalities, healthy, able-bodied participants exercised at moderate-to-vigorous intensity: in the treadmill analysis 3 there were 11 participants (8 male, 3 female; overall mean age 32.5 years, mean body mass 75.5 kg, mean height 1.79 m); for the cycle ergometer 4 there were 27 participants (20 male, 7 female; overall mean age 30.8 years, mean body mass 76.3 kg, mean height 1.79 m). Participants were required to be regular exercisers (30-min bouts, 3 times per week), non-smokers, and to be free of injury and illness.” Did the Authors evaluate sample size to ensure credibility of their analysis and conclusions? There are only 38 participants in this study. RESPONSE: Thank you for this important query. As noted above, the 38 participants came from two previous studies: a pilot treadmill study, [3], with 11 participants, and a cycle ergometer study, [4], with 27 participants. For the treadmill study, the sample size of n = 11 was chosen in accordance with the requirements of pilot studies, and no formal statistical power analysis was conducted. For the cycle ergometer study, an a priori statistical power and sample size estimate was included in the study protocol that was approved by our ethics committee. The details can be found in reference [4], as follows: “The sample size of n = 27 participants was estimated a priori by a statistical power calculation that used estimates of expected effect sizes and sample standard deviations obtained from previous studies in this lab, with the significance level of 5 % and a statistical power of 80 % (1 − β = 0.8).” In both cases, no post-hoc statistical power calculation was performed because observed effect sizes and their uncertainty bounds supersede any a priori estimates, and because “Post-hoc power estimates … have been shown to be logically invalid and practically misleading”; quotation from: Dziak JJ, Dierker LC, Abar B. The Interpretation of Statistical Power after the Data have been Gathered. Curr Psychol. 2020 Jun;39(3):870-877. https://doi.org/10.1007/s12144-018-0018-1"
}
]
},
{
"id": "331353",
"date": "24 Oct 2024",
"name": "Lauren Miutz",
"expertise": [
"Reviewer Expertise Exercise physiology",
"cerebrovascular physiology",
"sport-related concussion & exertional measures"
],
"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\nBrief description of article: Reanalyzed retrospective data to better identify a model of best fit for heart rate changes during exercise. The present study included a zero point and a pure delay in the heart rate model.\nRelevance: Although the research reported that the model including dead time (compared to the model without dead time) provided a “better fit,” is the this clinically meaningful. The researchers reported a change in percentage of fit, however in the field of clinical or non-clinical exercise physiology, heart rate (especially regarding exercise) is largely provided as a range. Thus, are the percentages provided, between the two models, clinically relevant within the field.\nMajor points:\n• Additional detail around the sample is needed, simply referencing the original work is not sufficient.\n• Information around resting average heart rate (cycle and treadmill) and average maximal heart rate (cycle and treadmill) should be provided.\nMinor point:\n• Training status of the participants should be reports as heart rate (and potentially the delay and amount of dead time) are often linked to one’s training status, especially aerobic capacity.\n• Interesting findings, however when reanalyzing retrospective data the researchers need to be careful the questions being answered is relevant and that adequate detail is provided to the reader, regardless of their knowledge surrounding the original study/data set.\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? 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": "12704",
"date": "01 Nov 2024",
"name": "Kenneth Hunt",
"role": "Author Response",
"response": "Dear Reviewers Many thanks for your detailed and constructive comments on our manuscript. We are pleased to provide a point-by-point response below. Changes to the manuscript have been implemented as noted below and submitted using “track changes” in the revised manuscript. With best wishes. Yours faithfully The authors Reviewer #2 Report and Response: Lauren Miutz Brief description of article: Reanalyzed retrospective data to better identify a model of best fit for heart rate changes during exercise. The present study included a zero point and a pure delay in the heart rate model. RESPONSE: We would like to thank you for your careful reading of our article and for your constructive comments. Please find below our point-by-point response. Relevance: Although the research reported that the model including dead time (compared to the model without dead time) provided a “better fit,” is the this [sic] clinically meaningful. The researchers reported a change in percentage of fit, however in the field of clinical or non-clinical exercise physiology, heart rate (especially regarding exercise) is largely provided as a range. Thus, are the percentages provided, between the two models, clinically relevant within the field. RESPONSE: Thank you for this remark regarding relevance for clinical or non-clinical exercise physiology. In a similar vein, Reviewer #1 requested more information regarding the clinical and physiological perspectives, and practical applications. To address these points, we added the following paragraph at the start of the Introduction: “Heart rate is an easy-to-measure physiological variable that can be used to characterise the intensity of exercise, both quantitatively and qualitatively using categories such as light, moderate and vigorous [10]. The ability to regulate heart rate during exercise using feedback control would therefore allow accurate prescription of training regimes in both clinical and non-clinical settings. Since feedback controllers require a model of the dynamic response of heart rate during exercise, it is important to first consider the fidelity of different model structures.” Furthermore, we would like to remark that, in the field of systems and control engineering—which is the field within which we authors work—model fidelity is usually provided either in absolute terms as a root-mean-square error (RMSE) or as a normalised RMSE, i.e. model fit, expressed in percent. We cannot definitively answer the question of whether the reported improvement in fit will be relevant to researchers or practitioners in other fields (e.g. exercise physiologists) and must leave it up to colleagues in those fields to assess our findings for themselves. Major points: • Additional detail around the sample is needed, simply referencing the original work is not sufficient. RESPONSE: Thank you for this recommendation (a similar request was made by Reviewer #1). We do agree that it would be helpful to the reader to have more information in the current article. As noted in our response to Reviewer #1, we have added more details to the Methods, as follows: “For both exercise modalities, healthy, able-bodied participants exercised at moderate-to-vigorous intensity: in the treadmill analysis 3 there were 11 participants (8 male, 3 female; overall mean age 32.5 years, mean body mass 75.5 kg, mean height 1.79 m); for the cycle ergometer 4 there were 27 participants (20 male, 7 female; overall mean age 30.8 years, mean body mass 76.3 kg, mean height 1.79 m). Participants were required to be regular exercisers (30-min bouts, 3 times per week), non-smokers, and to be free of injury and illness.” • Information around resting average heart rate (cycle and treadmill) and average maximal heart rate (cycle and treadmill) should be provided. RESPONSE: Thank you for this suggestion. We have added information on average maximal heart rate (cycle and treadmill) to the Results section, as quoted below. Unfortunately, we cannot provide average resting heart rate because recording was started at the onset of the PRBS input signal: resting heart rate was not recorded (resting HR played no role in the analysis). Text added to Results: “Average maximal heart rate for the treadmill was 158.4 bpm; for the cycle ergometer it was 140.2 bpm (this is in line with our setting the mean target heart rate for the CE to be 20 bpm lower than for the TM in order to achieve a similar level of perceived exertion [9]).” Minor point: • Training status of the participants should be reports [sic] as heart rate (and potentially the delay and amount of dead time) are often linked to one’s training status, especially aerobic capacity. RESPONSE: Thank you for this comment. As noted above, we have now provided information regarding participants’ training status: “Participants were required to be regular exercisers (30-min bouts, 3 times per week) …”. Beyond this requirement (it was a formal inclusion criterion), we did not record any further information in this regard. • Interesting findings, however when reanalyzing retrospective data the researchers need to be careful the questions being answered is relevant and that adequate detail is provided to the reader, regardless of their knowledge surrounding the original study/data set. RESPONSE: Many thanks for your observations, which are valuable. We hope that our responses and the corresponding revision of the manuscript now provide adequate detail independent of the original publications."
}
]
}
] | 1
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https://f1000research.com/articles/13-894
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https://f1000research.com/articles/13-1310/v1
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31 Oct 24
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{
"type": "Research Article",
"title": "Effect of thermocycling on flexural strength of dental CAD/CAM ceramics of variable thicknesses and structures: an in vitro study",
"authors": [
"Passent Ellakany",
"Yousif A. Al-Dulaijan",
"Nourhan M. Aly",
"Turki Alshehri",
"Shahad T. Alameer",
"Sultan Akhtar",
"Laila Al Dehailan",
"Yousif A. Al-Dulaijan",
"Nourhan M. Aly",
"Turki Alshehri",
"Shahad T. Alameer",
"Sultan Akhtar",
"Laila Al Dehailan"
],
"abstract": "Background This study examined the effect of thermocycling on the flexural strength properties of four CAD/CAM ceramic materials at different thicknesses.\n\nMethods Four CAD/CAM ceramics of different types: advanced lithium disilicate (ALD), zirconia-reinforced lithium silicate (ZLS) lithium disilicate (LD), and leucite reinforced (LE), and at three varying thicknesses 0.5, 1.0 and 1.5 mm were examined. After subjecting all specimens to 5000 thermomechanical cycles, flexural strength was determined using a universal testing apparatus. Scanning electron microscopy (SEM) was employed for analysis. Two factorial ANOVA models assessed the association of different factors (ceramic type and thickness) with flexural strength and elastic modulus. The 95% confidence intervals (CIs) and adjusted means were computed. A p-value < 0.05 was designated significant.\n\nResults ZLS exhibited the highest flexural strength at 1.5 mm thickness, while LD showed the highest Young’s modulus of elasticity. The lowest flexural strength was observed in the 0.5 mm thickness group. There were notable variations in flexural strength across all ceramic materials, with the highest adjusted mean strength in the ZLS group, ALD, LD, and LE, respectively. Additionally, significant differences were noted in ceramic thickness, with 1.5 mm thickness showing the highest strength and 0.5 mm thickness the lowest.\n\nConclusions Ceramic material thickness significantly impacts flexural strength, with 1.5 mm thickness deemed suitable for posterior restorations. Ceramic materials with zirconia fillers or matrix demonstrated higher flexural strength than other ceramics.",
"keywords": [
"CAD/CAM",
"Ceramics",
"Flexural Strength",
"Thickness",
"Composition"
],
"content": "Introduction\n\nDental ceramics have evolved to offer restorations with superior esthetic and mechanical characteristics, serving as efficient alternatives to metal-ceramic restorations.1 These dental ceramics can be categorized based on their fabrication method, composition, firing temperature, and microstructure.2 All-ceramic restorations can be fabricated using different methods, including conventional techniques like stacking and sintering, split casting and infusion, and heat- or dry-pressing methods, as well as through computer-aided design and computer-aided manufacturing (CAD/CAM) techniques.2,3 The homogeneity of ceramic CAD/CAM blocks has notably enhanced the strength of definitive prostheses by reducing crack development and defects compared to conventional ceramic fabrication methods.4 Lithium disilicate glass-ceramic (LD) is one of the most common ceramic materials, with its (SiO2-Li2O) composition minimizing microcracks and enhancing mechanical properties.5,6 Previous studies have demonstrated LD’s higher fracture resistance compared to leucite ceramics and improved flexural strength over lithium disilicate-strengthened lithium aluminosilicate glass.7,8 Leucite glass-ceramic is another option for high-esthetic and translucent all-ceramic restorations, with comparable fracture strength to feldspathic ceramics and resin nano-ceramic.9\n\nLithium silicate CAD/CAM ceramics reinforced with zirconia (ZLS) integrate tetragonal zirconia fillers to improve ceramic strength, making them capable of withstanding occlusal forces.10 Despite ZLS being challenging to section due to drill blunting,11 its high biaxial flexural strength values have bolstered its utility in fabricating various restorations, including implant-supported molar crowns, occlusal veneers, and endo-crown restorations.12\n\nAdvanced lithium disilicate (ALD), a recent addition to the market, comprises lithium disilicate (Li2Si2O5) and virgilite crystals which form a 0.5-μm-long needle-like shape within a zirconia glass matrix.13 Research reporting the mechanical properties of ALD ceramics is scarce.14,15 One of the published studies showed some positive results regarding the mechanical fatigue behavior of ALD, which is similar to LD but lower than lithium silicate-disilicate and Yttria-stabilized zirconia14 In contrast, another study reported that ALD had lower fracture toughness15 as well as lower flexural strengths when compared to LD.16\n\nThe thickness and composition of ceramic restorations have a direct impact on flexural strength and esthetics, where varying restoration thicknesses offer solutions for some clinical challenges.17 For example, thinner restorations can be used for ceramic veneers of high esthetics and translucency,18 while thicker ceramics are more suitable for full-coverage restorations.19 To create a restorative dental material that is highly sustainable, aesthetically pleasing, and safe, all of the material’s qualities must be thoroughly examined and tested.20 Since chewing and biting put occlusal stress on all restorative materials used for tooth restorations, proper flexural strength is considered essential.16 The maximum stress a material can withstand deformation under load is known as flexural strength.21 On the other hand, the minimal and conflicting findings on ALD highlight the need for further studies to comprehensively assess its mechanical properties.14–16 Additionally, understanding the impact of ceramic thickness and structure can guide the selection of appropriate restoration types for specific dental applications. Thus, this research aimed to evaluate the effect of thermocycling on the flexural strength of four CAD/CAM ceramics of varying thicknesses. According to the null hypothesis, no discernible relationship would be noticed between the flexural strength and the thickness and composition of CAD/CAM ceramics after exposure to thermocycling process.\n\n\nMethods\n\nFour CAD/CAM ceramics of low translucency and A1 shade were examined; advanced lithium disilicate (Cerec Tessera™, Sirona Dentsply, Milford, DE, USA; ALD), zirconia-reinforced lithium silicate (Celtra Duo®, Sirona Dentsply, Milford, DE, USA; ZLS), lithium disilicate (IPS E.max® CAD, Ivoclar Vivadent, Schaan, Liechtenstein; LD), and leucite reinforced (IPS Empress® CAD, Ivoclar Vivadent, Schaan, Liechtenstein; LE) as shown in Figure 1. Each ceramic type included 30 specimens, further categorized into three thicknesses of 0.5-, 1-, and 1.5mm. (n=10 specimens per thickness subgroup). As a result, 120 specimens made up the entire sample size that was evaluated in this study. In order to detect an effect size of 0.42, the total sample was computed using G*Power (Version 3.1.9.4), assuming a 5% alpha error and 80% research power. The least number of specimens required for each group was determined to be 9. However, 10 specimens were included to account for possible problems with the laboratory process.22 As a consequence, the number of subgroups multiplied by the number of members in each subgroup yielded 12 × 10 = 120 specimens as the total sample size.23\n\nThe specimens were sectioned utilizing a precision cutting device (Isomet 5000 machine; Buehler, Lake Bluff, IL, USA) under an abundance of water to produce the following thicknesses of 0.5, 1, and 1.5 mm × 4 mm × 12 mm. Following the specimens’ cutting, a 60-second polishing period was conducted utilizing silicon carbide discs (500-grit coarse) at 200 rpm in the presence of a water-cooling system. The polishing was executed employing a polishing device (MetaServ 250 Grinder-Polisher with Vector Power Head; Buehler, IL, USA). Post-polishing, the specimens were placed in a furnace of ceramic to crystallize. (Programat EP5010; Ivoclar Vivadent, Schann, Liechtenstein). Subsequently, an additional polishing step was performed utilizing the previously described polishing equipment and 400- and 600 grits of carbide discs in a moist atmosphere for 60 seconds at 200 rpm. To ensure dimensional consistency, a digital caliper (Mitutoyo Corp, Kawasaki, Japan) was employed to verify that all specimens maintained a thickness within 0.05 mm.23,24\n\nThe specimens went through a simulated aging protocol, undergoing 5000 thermomechanical cycles in a thermomechanical aging apparatus (Thermocycler THE-1100 machine; SD Mechatronik Feldkirchen, Westerham, Germany). Water baths ranging in temperature from 5°C to 55°C were used for the alternating cycles, with a 10-second interval between each bath and a 30-second immersion period. This simulation replicated the aging impact equivalent to six months of natural aging.25–28\n\nThe flexural strength assessment was done using the universal testing machine (Instron 8871 Universal Testing Machine; Instron, Shakopee, MN, USA). A rounded-end steel indenter that was specially made with a 2.5-mm radius was employed. The crosshead speed was set at 1 mm/min, and an axial load of 30 N was directed vertically at the center of the ceramic specimens until fracture happened.29 The maximum load at the point of fracture was noted in Newtons for each specimen.25 Then, megapascals (MPa) were used to calculate the flexural strength based on recommendations outlined in the International Organization for Standardization’s (ISO) 6872 Dentistry—Ceramic Materials.30\n\nEquations listed below were employed to compute the flexural strengths and elastic modulus of specimens.\n\nWhere (b) is the tested specimen’s width, (h) is its thickness, (L) is the distance between the two supporting arms, and (F) is the force applied till fracture in Newton. Elastic modulus = FL3/4bh3d where (d) is the deflection measured at (F), and (F) is the load imposed on the linear section of the stress-strain curve (N).27\n\nFor surface qualitative evaluation via scanning electron microscopy (SEM), a randomly selected specimen from each subgroup was chosen to examine the topography of each sample following fracture. The SEM analysis was done using a scanning electron microscope (Inspect S50 model; FEI Company, Moravia, Czech Republic) operating at an increasing voltage of 20 KV and magnifications of ×10000. To reduce the impact of charging and enhance the clarity of the image, the specimens underwent a gold-coating process before examination.24\n\nPlots (Q-Q plots and histograms), normality tests, and descriptive statistics were used to test for normality. All data showed normal distribution, so parametric analysis was adopted. Two factorial ANOVA models were performed to assess the association of different elements (type and thickness of tested ceramics) with flexural strength and elastic modulus. Calculations were done for adjusted means and 95% confidence intervals (CIs). P-value <0.05 was used as the significance threshold. Data analysis was done with Windows-based IBM SPSS (Version 26.0).\n\n\nResult\n\nTable 1 presents the flexural strengths and elastic moduli of the four studied ceramics at different thicknesses. At a thickness of 1.5 mm, ZLS exhibited the greatest flexural strength (mean (SD) = 309.08 (33.49)), while LE showed the most minor flexural strength (mean (SD)= 268.11 (7.48)).\n\nMoreover, at a 1.5 mm thickness, ZLS ceramic required the most significant amount of force to break (mean (SD) = 416.56 (74.55)) in contrast to the same thickness of LE, which required the least amount of force to be broken (mean (SD) = 204.04 (15.66)). Among the 1.5 mm thicknesses, ZLS had the highest Young’s modulus of elasticity (mean (SD)= 82.80 (12.35), while had the lowest (mean (SD)= 82.80 (12.35).\n\nThe 0.5mm thickness across all ceramic groups had the lowest flexural strength, elastic modulus, and forces to break. These values were significantly higher at 1.5 mm thickness when compared to 0.5- and 1-mm thicknesses, with ZLS exhibiting the highest values (mean (SD)= 309.08 (33.49), 82.80 (12.35), and 416.56 (74.55)) respectively.\n\nTable 2 and Figure 2 illustrate the association of flexural strength with ceramic type and thickness. The findings indicated significant variations in flexural strength between the materials, with ZLS exhibiting the highest adjusted mean stress (269.49 MPa), followed by LD (260.00 MPa), ALD (242.21 MPa), and LE (230.26 MPa). Additionally, the materials’ thickness was a major factor, with the 1.5 mm thickness demonstrating the highest strength (290.08 MPa) and the 0.5 mm thickness presenting the least strength (205.94 MPa).\n\nSEM images at ×10000 magnification showed the crystalline structure of ALD, ZLS, LD, and LE specimens (Figure 3). ZLS showed a homogenous crystalline matrix (Figure 3a). At the same time, LD had needle-shaped fine-grained crystals within a glassy matrix (Figure 3b). LE and ALD images showed numerous pores with leucite crystals and lithium aluminum silicate crystals incorporated in a glassy matrix, respectively (Figure 3c and 3d).\n\n\nDiscussion\n\nThis study assessed the flexural strength of four CAD/CAM ceramic materials of varying thicknesses and compositions. The results showed that 1.5 mm thickness in the ZLS group was the highest flexural strength. Similar findings were noted in ZLS of 1.5 mm thicknesses in terms of elasticity. The highest strength was noticed among the ZLS specimens, LD, ALD, and LE, respectively, which subsequently required higher force to fracture. Specimens with a thickness of 1.5 mm exhibited significantly greater strength compared to the 0.5 mm samples, which presented the least strength. Thus, the null hypothesis is rejected.\n\nDifferent thicknesses of ceramic material might yield varying flexural strength values on the ceramic materials. Ceramic materials of less thickness, such as 0.5 and 1mm, are suitable for minimally invasive procedures.31 Schweiger J et al.32 investigated three different types of CAD/CAM materials: LE, LD, and 3Y-TCP zirconia at five different thicknesses ranging from 0.4-1.6 mm. The lowest load required to fracture was recorded at the 0.4 mm thickness, while the highest load was required for the 1.6 mm thickness of zirconia, followed by LD and LE ceramics. This is consistent with the current study’s findings, where the 0.5 mm thickness of LE ceramics required the least force to fracture, while the 1.5 mm thickness of ZLS and LD required the highest force to fracture, respectively. The results of the flexural strength test of this study were compared to the readings of the biaxial flexural strength test described by Schweiger J et al.32 due to the lack of similar studies assessing the relation between varying ceramic thickness and the flexural strengths characteristic.\n\nIn assessing the relation between the ceramic composition of tested ceramics and flexural strength feature, ZLS of all thicknesses exhibited the highest flexural strengths compared to LD and ALD, respectively. Meanwhile, LE ceramics exhibited the least flexural strengths among all tested materials at different thicknesses. This comes in agreement with Attar et al.33 findings, which reported that zirconia-reinforced lithium silicate ceramics (Vita suprinity) of 2 mm thickness exhibited higher flexural strengths than LD and LE, respectively. Similar findings were stated by Elsaka et al.34 after assessing the flexural strengths and elastic moduli of Vita suprinity and LD of 1.2 mm thickness. The higher strengths and elastic modulus of zirconia-reinforced ceramics are related to the presence of ZrO2 particles in the glassy matrix as in SEM images, resulting in a higher resistance to crack propagation.33,34 In contrast, Corade et al.35 showed increased flexural strength of LD specimens of 1.5 mm compared to both ZLS and other zirconia reinforced lithium disilicate ceramics of different manufacturers (Vita suprinity and Rosetta). This might be referred to the different methods used in both studies.\n\nThe current results showed that LD reported higher flexural strength than ALD and LE ceramics. In agreement with these findings, another study reported that crystalized LD of 1 mm thickness exhibited higher flexural strength compared to ALD after exposure to different firing and glazing protocols.36 Similarly, another study displayed that the highest flexural strength was reported among LD specimens of 3 mm thickness contrasted to ALD.16 Furthermore, Sonmez et al.37 found that LD specimens of 1.2 mm thickness showed higher flexural strength than those of LE ceramics. These superior properties of LD might be due to the difference in composition, where LD includes a tiny amount of glass phase and lithium disilicate crystals, as shown in SEM.\n\nStrengths of this study included assessing the flexural strengths of the most used CAD/CAM ceramics, varying in thicknesses relevant to fabricating different esthetic restorations such as dental veneers, veneered restorations, and all-ceramic prostheses. Moreover, a thermocycling procedure was applied to simulate an aging process equivalent to 6 months intraorally. Additionally, the study evaluated the flexural strengths and topography of Cerec tessera (ALD) ceramics, a type of ceramic that is relatively new in the CAD/CAM realm and has not been extensively studied in the literature, especially in variable thicknesses.\n\nDespite the strengths, the study has several limitations; one major limitation is that it is an in vitro study, which may not fully represent the complex oral environment. Therefore, further clinical studies are required to assess different restoration designs and a wider range of dental materials to better simulate oral conditions. Moreover, the study only assessed low translucency ceramics, and future studies should consider evaluating different levels of translucency to understand their impact on flexural strengths more comprehensively.\n\n\nConclusions\n\nThe increase in ceramic thickness significantly impacts the flexural strength. A thickness of 1.5 mm was found to be optimum in restoring teeth in the posterior region or subjected to heavy occlusal load. Additionally, the composition of CAD/CAM ceramics has a crucial role in the flexural strength property. Dental ceramics, including zirconia fillers, are more resistant to deformation under masticatory loads than other glass ceramics. This was noted in ZLS ceramics. However, ALD requires further investigations to validate the current findings.",
"appendix": "Data and software availability\n\nAll the data analyzed during the study are included in the article.\n\nFigShare: Flexural strength of ceramics data set. Ellakany, Passent (2024) https://doi.org/10.6084/m9.figshare.27095080.v1\n\nThis project contains the following underlying data:\n\n• Flexural strength ceramics data.xlsx. figshare. Dataset. https://doi.org/10.6084/m9.figshare.27095080.v1\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nMavriqi L, Valente F, Murmura G, et al.: Lithium disilicate and zirconia reinforced lithium silicate glass-ceramics for CAD/CAM dental restorations: biocompatibility, mechanical and microstructural properties after crystallization. J. Dent. 2022; 119: 104054. PubMed Abstract | Publisher Full Text\n\nAl-Dulaijan YA, Aljubran HM, Alrayes NM, et al.: Clinical outcomes of single full-coverage lithium disilicate restorations: A systematic review. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nSonmez N, Gultekin P, Turp V, et al.: Evaluation of five CAD/CAM materials by microstructural characterization and mechanical tests: a comparative in vitro study. BMC Oral Health. 2018; 18: 1–3."
}
|
[
{
"id": "339059",
"date": "10 Dec 2024",
"name": "Gilan Altonbary",
"expertise": [
"Reviewer Expertise prosthodontics",
"CAD/CAM"
],
"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 are to be complimented for conducting this study. Its design is very good and materials and methods appropriate ,\n\nin the introduction section the authors mentioned that research reporting the mechanical properties of ALD is scarce however an invitro study by Freitas et al 2023 [Ref 1] investigated surface properties and fatigue mechanical behavior of advanced lithium disilicate (ALD), and compared it to a conventional lithium disilicate (LD) and to a translucent polycrystalline zirconia-based ceramic (4Y-PSZ) this study can also be included in the discussion section as it reported that (ALD) has lower roughness among the tested materials (lithium disilicate and yttrium-stabilized zirconia ceramics). Regarding flexural fatigue strength, ALD presented lower values and greater variability in mechanical performance (resulting in a lower structural reliability) when compared to the other materials\n\nin the conclusion section the authors stated that the increase in ceramic thickness significantly impacts the flexural strength according to the study results, however this was not fully addressed in the discussion; as the increase thickness of material from 0.5 to 1.5 mm lead to increase transformation toughness, Also, greater the thickness will decrease the bending force in ceramic material which explain increasing in flexural strength with higher thicknesses\nanother limitation for this invitro study is the specimens shape and design( please mention in the methodology section), which do not mimic the geometry of crown-bridge restorations.\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/13-1310
|
https://f1000research.com/articles/13-1309/v1
|
31 Oct 24
|
{
"type": "Research Article",
"title": "Energy efficient heating and ventilation of a factory hall by monitoring the indoor air climate",
"authors": [
"Yose Wandy",
"Ralf Gritzki",
"Markus Rösler",
"Alf Perschk",
"Clemens Felsmann",
"Yose Wandy",
"Ralf Gritzki",
"Alf Perschk",
"Clemens Felsmann"
],
"abstract": "Background Different usage scenarios and design guidelines were considered when planning a factory building and its ventilation system. Accordingly, it often makes sense to analyze the actual operating conditions again during subsequent operations in order to optimally adapt the air supply to the respective conditions in terms of demand-responsive ventilation. The aim is to ensure good indoor air quality and thermal comfort while significantly reducing energy consumption.\n\nMethods For this purpose, in addition to the sensors in the building management system, approximately 120 wireless sensors were installed in the occupied areas to measure the air temperature, operating temperature, humidity, and CO2. In this way the spatial and temporal distributions of temperature, humidity, and CO2 in the hall were visualized and evaluated to reduce the volume flows of the ventilation systems. The recorded data and findings were used to optimize ventilation systems by gaining a deeper understanding of indoor air flow.\n\nResults As part of the investigation, a considerable reduction in the air volume flows and thus the required energy consumption of the air handling units was achieved while maintaining the same thermal comfort. It was shown that the temperature field and indoor air quality were not negatively affected by the change in the air volume flow over a wide range.\n\nConclusions This was made possible by the well-designed ventilation system, which achieves a low-pulse, slightly stratified indoor airflow, and a structural envelope with very good thermal insulation.",
"keywords": [
"Indoor air climate",
"Factory hall",
"Energy consumption",
"Ventilation",
"Sensors"
],
"content": "Highlights\n\n\n\n• This study shows that it is possible to optimize the ventilation systems in a factory hall with a network of commercially available sensors for indoor climate and operate them economically.\n\n• The spatial and temporal distributions of temperature, humidity, and CO2 in the hall were visualized and evaluated to reduce the volume flows of the ventilation systems.\n\n• The recorded data and findings were used to optimize ventilation systems by gaining a deeper understanding of indoor air flow.\n\n• It was shown that the temperature field and indoor air quality were not negatively affected by the change in the air volume flow over a wide range.\n\n\n1. Introduction\n\nThis study uses the automotive industry as an example to discuss the possibilities for energy savings through demand-responsive ventilation. Automobile production can be roughly classified into press shops (production of body parts), body shops (welding and assembly of body parts), paint shops (painting body parts), and assembly shops. Figure 1 shows the classification of energy consumption according to the production areas of the automobile industry. The assembly line is responsible for almost a quarter of the total energy consumption, preceded by paint and body shops. HVAC systems are responsible for more than 65 % of the total energy consumption in the assembly, succeeding in other infrastructure systems, halls, and workplace lighting (Volkswagen AG, 2023).\n\nOn par with the paint shop, the assembly line also accounts for the highest energy consumption of HVAC systems. Almost one-third of the HVAC consumption in automobile manufacturing can be located in the assembly line. The main reason for this is that there are more workers in an assembly hall than in other manufacturing areas. In terms of occupant thermal comfort demand, Figure 2 shows that HVAC heating and electricity consumption resulting from space heating and electric drives in HVAC systems responding to the thermal comfort demand of approximately 36 % in total is higher than process-related HVAC consumption, that is, occupant comfort is more demanding than process-related HVAC energy consumption (Volkswagen AG, 2023, based on several locations).\n\nHVAC systems in factory halls are often generously dimensioned to ensure greater flexibility in hall utilization. Accordingly, it is important to develop and use efficient control systems to optimize HVAC control for current hall use. The aim is to find a compromise between the lowest possible energy consumption and the best possible thermal comfort. This is made possible by optimizing the required air volume flow based on a detailed assessment of the resulting air distribution.\n\nThe challenge when ventilating large rooms such as a factory hall is the ratio of a very large and high room to a small occupied zone (see Heiselberg et al.,1998). The ventilation system should be designed such that fresh air is always supplied to the occupied zone. The remaining room volume was of secondary importance. Additionally, vertical temperature gradients with higher temperatures in the upper hall area should be avoided to prevent energy loss. In other words, stratification in terms of indoor air quality is helpful; however, stratification in terms of temperature should not occur. If such a comfortable condition is achieved at a certain ventilation level, for example, through diffusers close to the floor, it should be maintained with every optimization. Ensuring this is difficult because of the complex interplay between the different types of ventilation and thermal loads in indoor air flow.\n\nAccordingly, the aim of the studies presented here is to identify ways to reduce electrical and thermal energy consumption while ensuring thermal comfort and indoor air quality. This was achieved by monitoring the climatic conditions in several representative areas of the hall in great detail, both spatially and temporally. Various operating parameters for the HVAC control system were varied, the effects of these variations on the indoor climate were measured, and the achievable energy-saving effects and effects on indoor air quality were determined. This paper presents the corresponding results for both summer and winter cases and analyzes them in terms of potential energy savings.\n\n\n2. Methods\n\nThis article describes an experiment and field test conducted to improve the energy efficiency and effectiveness of an HVAC system of a factory building in the automotive industry in Września, Poland, using indoor air quality parameters. The factory building was built in 2014 and is divided into two sections. The northern section (Figure 3, right) of the hall is the main assembly line area (Montage); it stretches over 475 m in length, whereas the southern section of the hall, which has a length of 375 m, is reserved for the finishing area (Figure 3, left). In the finishing area the manufactured cars are processed, washed and inspected thoroughly before the final test drive, this area of the hall is significantly narrower than the assembly line area.\n\nThe assembly area (Montage; M01 to M16) is served by 16 HVAC systems, whereas the finishing area is served by six HVAC systems (F01 to F06). However, with regard to the production process, the HVAC in the finish area is not only used to condition the building area, but also to supply quality control and test drive, for example, roller test rig. This limits the design of the experiment; only the main assembly line area (M01–M16) can be used for experiments with. The 16 HVAC supply systems installed in the assembly hall are presented in Table 1. The HVAC systems in the finish line were outside the scope of this study, and remained unchanged throughout the experiment. Each of the 16 HVAC systems was equipped with two ventilator resps. fans on the supply side, and two fans on the exhaust side. The supply air fans of M01-M04 have a nominal electric power of 18.5 kW, while all other fans have a power of 22 kW. Exhaust air fans operate at nominal power of 18.5 kW, 22 kW resp. 30 kW, depending on the system. They can deliver air flow rates of up to 63,000 m3/h or 75,000 m3/h at the nominal power. In total, 64 fans in the assembly area required 676 kW of fan power on the supply air side and 740 kW of fan power on the exhaust air side.\n\nThe floor area and nominal supply air volume flow rates of dedicated HVAC systems for the complete hall are summarized in Table 2.\n\nBased on data given, the floor related supply air volume flow rate of the HVAC system for the assembly area for this case study is calculated at 15.69 m3/hm2. However, owing to the narrow construction of the building and higher demands on air quality as a result of the exhaust gases released, the finishing area has a much higher specific volumetric flow rate than the assembly line area. In view of the very high air quality recorded in the hall so far, the question arises as to whether it’s necessary to deliver volumetric flow rates of air of up to 22.70 m3/hm2. These are the design state conditions with typical flow rates for assembling halls between 20 m3/hm2 and 30 m3/hm2 (VDI 3802, 2014). A reduction in the volume flow rate leads to a significant reduction in the fan electric power consumption for air transport and distribution.\n\nThe operation of fans is governed by a consistent set of laws dictated by speed, power, and pressure. If the speed (RPM) of a fan is altered, it will reliably result in a corresponding change in the power required to run it at the new RPM, as well as the pressure rise it generates. The volumetric flow rate of the fans was calculated based on the relationship between the flow power of the fan and its speed (VDI 6014, 2016).\n\nV̇1,V̇2 = Volumetric Flow Rate [m3h]\n\nN2,N2 = Fan Speed [RPM].\n\nSpeed control by frequency control flow power is not very different from the electrical power of the fan; therefore, these relations are often used to estimate electrical power consumption in a very simplified way (Bureau of Energy Efficiency, 2023) and can be treated in the same way here or by (VDI 6014, 2016). Because the air flow is proportional to the speed of the fan, slowing down the fan also means a linear reduction in the volumetric flow rate, so that a 10 % reduction in volumetric flow rate will lower the electrical power demand by approximately 30%.\n\nThe HVAC systems listed in Table 1 are shown on the right side of Figure 3, which shows the outline of the supply air ventilation zone according to the distribution of the supply air duct system in the hall. The heating demand of the building was covered by using direct gas heaters and heat recovery in the HVAC system. They do not have humidifying, dehumidifying, or cooling capabilities. Air is supplied close to the occupied zone and workplaces by displacement, such as diffusers (for low momentum stratified flow) at a height of approximately 3 m. In this way, the ventilation system generates a uniform velocity and temperature field in the complete hall. During the heating period, the HVAC system was set to establish a 20.5 °C of room air temperature under all conditions in this study, measured at two different positions at approximately 3 m height for each system. Figure 4 shows a schematic of the parts used in the HVAC system installed in the factory hall, which applies to each of the 16 HVAC systems.\n\nAs mentioned above, each ventilation system was equipped with temperature and CO2 sensors close to the East and West walls of the building at a height of approximately 3 m. This is very helpful, but not enough, to monitor thermal comfort and indoor air quality close to the workplace. Therefore, a network of approximately 120 sensors for air temperature and humidity, and some additional sensors for operative temperature and CO2 were installed. However, this was not sufficient to obtain the details of the indoor air climate of the complete hall. Thus, four zones were recognized as representative based on the production process, and worker occupancy was defined in the hall. The locations of these zones are shown in Figure 5. Of these zones, Zone 4 was selected for the reduction of the air flow rates and for this study. In this area, there are several windshield gluing machines and workers performing manual work, as well as a break area for workers. Zone 4 was supplied by the ventilation systems M05–M08.\n\nFigure 6 shows an overview of the installations used to measure temperature, relative humidity, and CO2 in zone 4 as an example. The setup consists of a vertical air temperature and humidity profile within the reach of the server transmitter area with nine–ten sensors. The reason for this is to measure the temperature gradient from floor to ceiling, so that we can ensure that there are no large temperature differences that could cause unpleasant draughts. The vertical distance between the sensors was 1 m, and the uppermost sensor was fixed to the bottom of the roof frame. In addition, there were two to three “smaller” vertical temperature profiles with four to five sensors spaced 2 m apart. Operative temperature and CO2 sensors were installed at a height of approximately 1.50-1.60 m, close to the worker’s area.\n\nFigure 7 shows the detailed positions of the sensors in relation to the relevant nearby facilities, such as the break room, windscreen bonding system, manipulators, and screws. Sensor S1 was placed in proximity to the air supply duct of the HVAC system. Five Sensors were installed on S4 at regular distances starting from 1.5 m height to 3 m, 5 m, 7 m, and 9 m, respectively, to monitor the room temperature at the working level and to monitor the vertical temperature gradient in the hall. In Figure 8, examples of the installed routers, gateways, and sensors used in this study are shown in Figure 8.\n\nThe developed system was built following the approach by the authors (Arendt et al., 2018), and in-depth knowledge of the structure and structural elements of the building was not required. The approach to hardware development was expandable and exchangeable with other possibilities of data inclusion.\n\nThe sensors used to measure temperature and humidity are from Technoline (TX29 DTH-IT) and are capable of transmitting the measured data at a frequency of 868 MHz. All sensors were calibrated accordingly prior to use, and the error tolerances were approximately +-0.3 K and +-5 %, respectively. To upload the measured data to the web servers of TU Dresden, the appropriate receiver (JeeLink) must be configured on a Raspberry Pi (RPi) server. Each RPi Server has a coverage of 50 m –100 m and can manage 30 air temperature/humidity sensors, as well as two to three operative temperature sensors and one CO2 sensor. The respective FHEM OpenSource-based server for data management also operates on this server. The wireless sensors collect data and send them through RPi servers and a gateway to the database server at TU Dresden. The data are visualized to observe the experiments online and, if necessary, to immediately react to overshooting. Figure 9 shows the design of the communication structure of the measurement system.\n\nThe sensor nodes remained in operation in 2019 and 2020. The analysis presented here focused on the dataset from the winter months of both 2019 and 2020. Three conditions were chosen from the dataset: March 2019 (Condition 1 or C1), April/May 2019 (Condition 2 or C2), and February/March 2020 (Condition 3 or C3). For convenience, the three conditions are mostly referred to as C1, C2, and C3, respectively. The outside temperature was between -5 °C and 20 °C in March 2019 and between -3 °C and 28 °C in April 2019. In the winter period from February to March 2020, the outdoor temperature was between -17 °C and 20 °C (Weather Spark, 2019, 2022). The three time slots are shown in Figure 10.\n\nThe objective is to investigate the potential for energy savings for the HVAC system owing to volume flow reduction while maintaining acceptable air quality and thermal comfort levels. This is achieved by varying the airflow rates (C1, C2, and C3) and observing how these changes impact the indoor climate by conducting measurements. The method of varying the air flow rates may not be systematic, but some special conditions stopped the systematic investigations in autumn 2019, especially in 2020. Therefore, we switched back to higher airflow rates after a stepwise reduction in the spring of 2019. Nevertheless, there were sufficient data for analysis.\n\nTable 3 provides information on the test conditions conducted in accordance with the time of year, power requirement, and volumetric flow rate. The “Nominal Condition” column shows the standard power requirement and volumetric flow rate of 22 kW and 2 × 37,500 m3/h respectively. Condition C1 (from 1st March–31st March 2019) had a lower calculated power requirement of 12 kW at a volumetric flow rate of 2 × 31,000 m3/h. This was the starting point of our investigation because the operator became aware of the data of the building management system that it is not necessary to run the HVAC system at maximum capacity. Condition C2 (from 18th April to 18th May2019) had the lowest calculated power requirement of 3.5 kW at a volumetric flow rate of 2 × 20,000 m3/h.\n\nSimilarly, condition C3 (from 20th February to 20th March 2020) had a calculated power requirement of 8.5 kW at a volumetric flow rate of 2 × 27,000 m3/h. On condition 3 (C3), the fans were reduced to approximately 8.5 kW or 40% of the electrical power and on condition 2 (C2) to about 3.5 kW or about 13.75% of the nominal power.\n\nThe power requirements data were calculated using VDI 6014 (2016) and compared to the data delivered by the building management system. In the case of the supply system, the data coincide well, but for the exhaust side, the power requirement is always lower because the short-duct system generates lower pressure losses than the supply system.\n\nIt should also be noted that further reductions can be achieved by further reducing the air flow rate or by switching off the ventilation at night or when there is no human presence, thus leading to further energy savings. Systems for monitoring emissions, temperature, and relative humidity are recommended so that the HVAC system can be controlled to achieve the defined thresholds.\n\n\n3. Results & Discussion\n\nAt the nominal point, each of the two supply and two exhaust air fans per HVAC system for the area requires 22 kW of electrical power and delivers up to 37.500 m3/h of supply and exhaust air, respectively. During the start of the experiment in winter 2019 (C1), the HVAC system was running at a partial load compared to its nominal capacity, and the fans were operating at approximately 12 kW or 55% of the nominal electrical power. Even under these conditions, the effect of the existing energy-saving measures is noticeable.\n\nFigure 11 shows the electrical power consumption profile of the two supply air (supply 1 and 2) and the two exhaust air (exhaust 1 and 2) fans. The fans are switched off on weekends (no production) using timer controls, which accounts for the intermittent absence of energy consumption in the graphs.\n\nFigure 12 shows the air temperature directly in front of an HVAC supply air outlet (Figure 7, S1), whereas Figure 13 shows the room air temperature in the nearby working area (Figure 7 and S4). The mean difference between C1 and C3 was approximately 1 K when comparing the room air temperature values under all three conditions. The air temperatures during C1 and C3 also followed the weekday–weekend heating profile of the production site. C2 showed higher room temperatures in general, owing to the higher outdoor air temperature between April and May 2019 compared to February and March. In contrast to the supply air temperature at C1 and C3, the supply air temperature of C2 approximately represents the outdoor air temperature because the heating module was shut off during the warmer season transition time (April to May). This can also be observed in Figure 13, where the room air temperature moves above the desired 20.5 °C threshold and does not follow the weekday-weekend heating profile.\n\nFigure 14 (a), (b), and (c) show the vertical temperature profiles in the hall for all three test conditions. The temperature at 1,5 m height is often higher than that at 3 m because the supply openings are at 3 m.\n\nBecause of internal heat gains, the supply air temperature is often lower than the room air temperature. The temperature is highest at 7 m. At 9 m, the temperature drops again because the sensor is directly below the ceiling and close to or almost adjacent to the cold outside air. This vertical temperature difference can be clearly observed in Figure 14 (a) and Figure 14 (b). During the seasonal transition C2, as shown in Figure 14 (c), the measured air temperatures were closer to each other along the height.\n\nOverall, there is no difference in the thermal and air flow situation in the hall when comparing conditions C1, C2, and C3. This means that the indoor airflow and thermal stratification seem to be independent of the airflow rate within the range between C1 and C2. The already good situation in the indoor climate of the hall is not affected by reducing the air volume rates within the limits discussed above. For a comprehensive assessment, humidity and CO2 levels should be evaluated in the same manner.\n\nThe relative humidity measurement data for all three conditions (Figure 15 (a), (b), and (c)) show little to no differences along the height.\n\nFigure 16 shows the CO2 measurement data for all the three test conditions. In general, the measured CO2 concentration was in the 400–700 ppm band. The CO2 concentrations during the C1 and C3 test periods were higher than the CO2 concentration measured during the C2 test period. The higher concentration can be explained by the use of direct gas heating in the HVAC system during the test periods C1 and C3, which represent the 2019 and 2020 heating periods, respectively. In both cases, the difference was quite small, indicating that the CO2 concentration was well below the Pettenkofer limit of 1,000 ppm. This knowledge is relevant for worker safety because it shows that the direct gas heater does not cause any significant increase in CO2 emissions. Overall, this also highlights that the change or reduction in the flow rate under the chosen conditions does not negatively affect the air conditions, as can also be seen from the temperature and relative humidity results. According to the trends in globally averaged CO2 determined from NOAA Global Monitoring Laboratory measurements, the average CO2 concentration of outdoor air between 2019 and 2020 lies between 409 ppm and 411 ppm (Lan et al., 2023).\n\nFinally, Table 4 displays the volumetric flow rate and the measured energy consumption of the three different conditions (C1, C2, and C3) during field testing. The first column lists the condition numbers, and the second column indicates the date and time for each condition. The third column shows the volumetric flow rate in cubic meters per hour (m3/h) under each condition. The fourth and fifth columns indicate the energy consumption in kilowatts (kWh) for the supply and exhaust fans, respectively. Energy consumption was calculated using the data delivered by the building management system for the selected time period.\n\nOverall, this table provides an overview of the volumetric flow rates and electrical energy consumption under the three conditions in this study. We only discuss electrical energy, although there are also savings in gas consumption, which is a subject for another publication. It is clear that energy consumption varies significantly among the three conditions. Condition C1 had a volumetric flow rate of 2 × 31,000 m3/h, resulting in the highest energy consumption of 16,151 kWh (10,132 kWh for supply fans and 6,019 kWh for exhaust fans).\n\nIn contrast, condition C3, with a volumetric flow rate of 2 × 27,000 m3/h, consumed 14,965 kWh (9,351 kWh for the outlet fans and 5,614 kWh for the exhaust fans). Finally, condition C2 had the lowest energy consumption of 4,540 kWh (2,798 kWh for the supply fans and 1,742 kWh for the exhaust fans), with a volumetric flow rate of 2 × 20,000 m3/h.\n\nComparing the energy consumption between the three conditions, it is clear that condition C3 had lower energy consumption than condition C1, with a significant energy saving of 1,186 kWh compared to condition C1. Furthermore, condition C2, which had the lowest volumetric flow rate compared to the other two conditions, resulted in a noteworthy reduction in the energy consumption of 11,611 kWh when compared to the energy consumed in condition C1.\n\nOverall, significant energy savings can be achieved by optimizing the volumetric flow rate and operating conditions, taking into account the current processes, and by running a network of monitoring sensors, as demonstrated by the lower energy consumption in conditions C2 and C3 compared to condition C1.\n\n\n4. Conclusion\n\nIn this study, we have demonstrated a method of using wireless air temperature, humidity, and CO2 sensors in an automotive factory to gain information about local room air conditions. This information is used to improve the energy performance of HVAC systems. Approximately 120 sensors were installed at different locations and showed the data results within three test conditions, C1 with 62,000 m3/h, C2 with 40,000 m3/h, and C3 with 54,000 m3/h of supply air per ventilation system.\n\nDuring the heating period, the HVAC systems were set to maintain a room temperature of 20.5 °C. When comparing the room air temperature values for all three test conditions, the difference between the two winter use cases (C1 and C3) was minimal. During transitional period C2, the room temperatures were higher than those of C1 and C3. This was caused by the warmer outdoor air temperature between April and May 2019 compared to the months of February and March of C1 and C3. The vertical temperature sensor values in the hall for all three test conditions were also discussed. The measurements showed a uniform temperature distribution over the height (less than 1 K spread). This is an indicator of the excellent effect of the air outlets/diffusers installed in the factory. The relative humidity data also showed very small differences along the height for all the three test conditions. The CO2 measurement data over the period under all three test conditions are also presented and discussed. The CO2 concentration was observed to be below the optimal threshold of 700 ppm for all three test conditions. The slightly higher CO2 concentrations under the three conditions can be explained by the use of direct gas air heaters in the HVAC system during the heating season.\n\nThe data show that the differences between the measured temperature and CO2 values under different conditions are negligible, although the volumetric flow rate is reduced from approximately 62,000 m3/h to approximately 54,000 m3/h and 40,000 m3/h for the supply and exhaust air, respectively. The comparison of energy consumption among the three conditions revealed that condition C3 consumed less energy than condition C1, resulting in significant savings of 1,186 kWh. Additionally, condition C2, with a lower volumetric flow rate than the other two conditions, achieved a substantial energy savings of 11,611 kWh compared to condition C1. It was shown that electrical energy savings of over 60% could be achieved for the reduced flow rate, with no significant negative impact on the temperature, humidity, and CO2 concentration in the work areas.\n\nThe results of this study can, in turn, be used for decision support or the optimization of HVAC systems. This approach using low-cost wireless sensors can provide an interesting way to combine spatially and temporally highly resolved measured data from the network of any given area with an appropriate control algorithm to create a dynamic control environment. The use case presented here shows this for three different outdoor and indoor air conditions in a large industrial environment, although a static-control approach was used. The sensors have benefits owing to their minimal deployment effort and should be further investigated in the future, for example, on a larger scale, in a different industrial area, or with a different control approach. In addition, an accurate comfort study can easily be conducted for any specific location. Different types of machinery used in the area can also be studied, as emissions such as volatile organic compounds (VOCs) can affect indoor air quality and should be considered in future studies. It should be noted that this study on reducing airflow rates by closely monitoring indoor air was carried out in consultation with the Health and Safety Authorities.\n\nFollowing the removal of the mobile sensor network at the end of the experiments, the factory fitted the hall with additional stationary sensors for temperature, humidity, CO2 and NOx. By monitoring the data of these quantities and maintaining good climatic conditions in the hall, the airflow was gradually reduced to find an acceptable minimum close to the C2 condition, considering the technical requirements of the ventilation system. Finally, a specific air flow rate between 7 m3/(hm2) and 9 m3/(hm2), depending on the season, was determined for this assembly hall under the given conditions, resulting in an electrical power of approximately 3 kW per fan.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability statement\n\nZenodo: Dataset for article submission 153972 in Journal F1000Research (1.0) [Data set], https://doi.org/10.5281/zenodo.13773811 (Roesler, 2024).\n\nThe project contains following underlying data (all in one xlsx-file including selected diagrams):\n\n• Energy demand of ventilators\n\n• Sensor data of air temperature and relative humidity\n\n• Sensor data of CO2-level\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 thank the experts from the energy management and technology of the factory in Września for many helpful discussions, much information from a practical point of view, and the management of the ventilation systems.\n\n\nReferences\n\nArendt M, Haupt L, Kremonke A, et al.: Entwicklung eines vernetzten Systems zur Erfassung, Visualisierung und Auswertung von Messdaten sowie zur Ansteuerung von Aktoren – Teil 1. GI - Gebäudetechnik in Wissenschaft & Praxis. 2018; 2: pp. 144–155.\n\nBureau of Energy Efficiency: Fans and Blowers; Government of India. 4th Floor, Sewa Bhawan. R. K. Puram, New Delhi - 110066 (INDIA): Ministry of Power; 2023. Last visited: 11.02.2024 Reference Source\n\nHeiselberg P, Murakami S, Roulet C-A: Ventilation of Large Spaces in Buildings, Analysis and Prediction Technics. IEA, Energy Conservation in Buildings and Community Systems. Annex 26: Ventilation of Large Enclosures. ISSN 1395-7953 R9803. Aalborg, Denmark: Aalborg University; 1998. Reference Source\n\nLan X, Tans P, Thoning K: Trends in globally-averaged CO2 determined from NOAA Global Monitoring Laboratory measurements. Version 2023-07.2023. Publisher Full Text\n\nRoesler M: Dataset for article submission 153972 in Journal F1000Research (1.0). [Data set]. Zenodo. 2024. Publisher Full Text\n\nVDI-Gesellschaft Bauen und Gebäudetechnik: Air conditioning systems for factories, Part 1. VDI Verein Deutscher Ingenieure e.V. Düsseldorf. 2014-09. Beuth-Verlag; 2014.\n\nVDI-Gesellschaft Bauen und Gebäudetechnik: Energy conservation by application of variable speed drives (VSD) in building services, VDI Verein Deutscher Ingenieure e.V. Düsseldorf. 2016-12. Beuth-Verlag; 2016.\n\nVolkswagen AG: Energy consumption distribution according to production areas and process [Unpublished data]. Volkswagen AG.2023.\n\n2019 Weather History in Poznań, WeatherSpark.com, Cedar Lake Ventures, Inc: 2500 Shadywood Rd Ste 510 Excelsior, MN 55331-6203 United States.2019. Last visited: 11.02.2024. Reference Source\n\n2022 Weather History in Poznań, WeatherSpark.com, Cedar Lake Ventures, Inc: 2500 Shadywood Rd Ste 510 Excelsior, MN 55331-6203 United States.2022. Last visited: 11.02.2024. Reference Source"
}
|
[
{
"id": "342001",
"date": "27 Nov 2024",
"name": "Asit Kumar Mishra",
"expertise": [
"Reviewer Expertise indoor climate monitoring and optimization",
"indoor climate and occupant health",
"sustainable indoor conditioning",
"healthy buildings"
],
"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 an interesting work and well executed. I would strongly advise the energy part to be combined and made into a stronger paper. Also, please present the detailed workings. It would seem authors are assuming readers will somehow read their mind. Details regarding sensor positioning, which sensors went where, why, recirculation fraction, how did the changes impact indoor conditions, these need to be provided and discussed.\n\nAbstract - 120 sensors sounds like a big number without an idea on the floor space. Also, why not mention what kind of factory is being considered?\nResults in Abstract needs more values. How do readers understand that thermal comfort and IAQ were indeed not compromised?\n\n\"vertical temperature gradients with higher temperatures in the upper hall area should be avoided to prevent energy loss.\" - this is not clear cut. What if i have a warm to cold gradient from floor to ceiling in a heating dominated climate. Why is that problematic? Introduction lacks reference to existing literature - what is the gap that authors are trying to address, has this approach really never been used? Table 1 and 2 - it is not clear how much of the supplied air is recirculated and how much is outdoor air \"ventilator resps. fans\" please avoid shortening words How did authors decide on position of the 120 sensors?\nThis needs a clearer description. At first glance, it is not even apparent how many sensors of what type are present per unit floor area. We need to understand where each type of sensor is positioned and what is the SOP used to determine positioning.\n\nI am missing the recirculation vs outdoor air and corresponding change in energy usage discussion and results. \"switching off the ventilation at night ...\" do the floors receive outdoor air during night, when there is no worker on floor as well? Need some information on occupant activity (met rates) and clothing For a factory floor, particulate matter and VOC data would also be relevant. CO2 could work as a proxy but we are not sure how good of a proxy it would be I am not sure why the energy saved for heating (gas) is part of another publication? Also, I would like to see some discussion on how things changed when the flow was reduced - the conditions still seem comfortable but there were some changes as would be expected when you reduce the air supply. This needs to be analyzed. Were there any feedback from the people working on the floors?\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?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1309
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https://f1000research.com/articles/13-1308/v1
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31 Oct 24
|
{
"type": "Research Article",
"title": "Development and validation of a Knowledge, Attitudes and Practices (KAP) questionnaire for healthcare professionals on environmental sustainability in healthcare in Southern Africa",
"authors": [
"Helga Lister",
"Karien Mostert",
"Tanita Botha",
"Emma Field",
"Danté Knock",
"Natasha Mubi",
"Stefani Odendaal",
"Megan Rohde",
"Filip Maric",
"Helga Lister",
"Karien Mostert",
"Tanita Botha",
"Emma Field",
"Danté Knock",
"Natasha Mubi",
"Stefani Odendaal",
"Megan Rohde"
],
"abstract": "Background Global environmental degradation is increasingly driving poor health outcomes worldwide. Healthcare systems and services are often not environmentally sustainable and compound the problem, while healthcare professionals are also recognised as key leaders in advancing sustainable healthcare. To adopt this leadership position, healthcare professionals’ knowledge, attitudes, and practices regarding environmental sustainability in healthcare must be established. This article reports the development and validation of a new instrument for this purpose that corresponds to the specificities of the Southern African context.\n\nMethods Questionnaire development followed a seven-stage process. Information was obtained from a 2021 study titled ‘South African Healthcare Professionals’ Knowledge, Attitudes, and Practices Regarding Environmental Sustainability in Healthcare: A Mixed-Methods Study’ to develop the instrument. Information was also sourced from the literature regarding environmental sustainability and healthcare to generate the first questionnaire with 29 items. The following stages included two rounds of expert input, separated by a pilot study with the target population to receive feedback regarding the instrument’s structure, relevance, and length. Content validity was determined through statistical analysis.\n\nResults Feedback was received from nine experts in stage two and 13 pilot-study participants in stage four and incorporated to improve the questionnaire. In stage six, the questionnaire was rated by seven experts. The content validity index of the questionnaire was calculated at two different stages, after which the indices were compared. Following a final edit, the questionnaire has 24 questionnaire items. The closing analysis calculated the scale content validity index average (S-CVI/Ave) of 0,922; this indicates that the final questionnaire has excellent content validity.\n\nConclusion A questionnaire that assesses the knowledge, attitudes and practices of healthcare professionals regarding environmental sustainability in Southern Africa has been developed and validated. This questionnaire can now be used for further studies in Southern Africa.",
"keywords": [
"Content validity",
"knowledge attitudes and practices",
"healthcare",
"environmental sustainability",
"Southern Africa",
"questionnaire development"
],
"content": "Introduction\n\nGlobal environmental degradation includes increasing global warming, freshwater shortages, loss of biodiversity, and exhaustion of natural resources, amongst others. The effects of global environmental degradation are becoming increasingly evident.1–4 Noncommunicable diseases account for 38 million deaths annually, and many of the risk factors of these are thought to have an environmental origin.5 Despite substantial and alarming evidence that biodiversity loss and climate change are inextricably linked to poor health outcomes, globally, many people are unaware of these far-reaching implications. A 2018 literature review demonstrated that most healthcare professionals realise that global environmental degradation is occurring, and they are aware of its detrimental effects on people’s health; yet, many healthcare professionals also recognise that they have inadequate knowledge on the topic.6\n\nThe World Health Organisation defines the healthcare sector as “all organisations, institutions and resources that are devoted to producing health actions”.7 Health actions have the chief purpose of improving health and are rooted in the ethical principle of “do no harm”.8 Ironically, many actions and practices in healthcare compound the effects of global environmental change and its associated health risks through their environmental footprint.9 In 2016, healthcare professionals were identified as key leaders in combatting the effects of global environmental degradation.10 Several ways in which healthcare professionals can take action have been highlighted, including raising awareness of environmental change as a universal health matter, advocating for mitigation strategies and sustainable solutions in the health sector and surrounding environments, and advocating for vulnerable groups who experience health inequity related to global environmental degradation.10,11\n\nGlobal surveys have been conducted to determine the perspective of healthcare professionals regarding global environmental degradation as a health concern.6 Survey participants understood that global environmental degradation is happening and recognised that humans are its main driver. Participants felt responsible for educating the public and policymakers about the problem but identified personal, professional and societal barriers as preventing them from doing so.10 Other various factors preventing healthcare professionals from adopting sustainable practices including a lack of knowledge, time constraints, the perception that their efforts would not make a worthwhile difference, limited finances and inadequate infrastructure.1,6,10,12,13 Limited or non-existent policies, subsequent lack of implementation, and conflicts between environmental policies and policies focusing on economic development also affect the attainability of environmental sustainability.14\n\nNotably, African countries are usually poorly represented in such surveys with South Africa often providing the largest representation among African countries.6 Southern African countries are particularly susceptible to global environmental degradation as they have interconnected social and environmental vulnerabilities. These include, for example, severe environmental degradation, high levels of inequality and poverty, an abundance of weather-sensitive diseases, limited infrastructure and limited financial means to effectively prepare for extreme weather events.15–17 Southern Africa thus faces extensive and compounding challenges related to global environmental degradation and its health impacts and needs better representation in relevant studies.\n\nTo unlock and increase the potential of Southern African healthcare professionals contributing to the improvement of environmental sustainability, a greater understanding of the current knowledge, attitude and practice (KAP) of healthcare professionals regarding environmental sustainability in healthcare is imperative. KAP studies are particularly useful in unfamiliar areas of research and are frequently used in healthcare as they can serve to combine both qualitative and quantitative data.18–20 In our research, studying KAP focused on gaining insight into Knowledge: what healthcare professionals know about environmental sustainability, Attitude: healthcare professionals’ feelings and opinions about environmental sustainability and Practice: what healthcare professionals do regarding environmental sustainability in practice.\n\nIn 2021, a study titled ‘South African Healthcare Professionals’ Knowledge, Attitudes, and Practices Regarding Environmental Sustainability in Healthcare: A Mixed-Methods Study’ was conducted at the University of Pretoria in the Health Sciences Faculty.21 The study participants included registered South African audiologists, occupational therapists, physiotherapists, and speech-language pathologists. A convergent mixed-methods design was utilised with data collection in parallel quantitative and qualitative phases. A questionnaire was used in the quantitative phase to obtain information regarding the KAP of environmental sustainability in healthcare, while focus group discussions using open-ended questions were employed in the qualitative phase, followed by deductive thematic analysis of the discussion transcripts.21 Although this study provides useful insights into the topic, the context was limited to the nation of South Africa.21 To make the instrument applicable to the broader Southern African context encompassing Namibia, Zimbabwe, Angola, Eswatini, Lesotho, Zambia, and Mozambique, it is necessary to develop and validate a new KAP questionnaire that can serve as an accurate measure of the KAP of healthcare professionals in this unique geographic region.\n\nThis article’s research built on the results of our previous study to develop and validate an instrument for assessing the KAP of healthcare professionals on environmental sustainability in healthcare in Southern Africa. This questionnaire can provide invaluable insight into knowledge gaps, current practices, and healthcare professionals’ attitudes and willingness to take environmental responsibility and action. The inclusion of barriers and education sections in the questionnaire will additionally assist in addressing challenges and implementing sustainable healthcare education to advance environmental sustainability in Southern Africa.6\n\n\nMethods\n\nThe study made use of a descriptive research design to develop and validate a KAP questionnaire as an instrument to collect quantitative and qualitative data on the KAP of healthcare professionals regarding environmental sustainability in healthcare in Southern Africa.\n\nThe development and validation of the KAP questionnaire consisted of a six-stage process:\n\n• Stage one: A mixed-methods study from 2021, together with updated literature, served as a starting point to generate the items used in the initial design of the first version of the questionnaire.\n\n• Stage two: An expert panel evaluated the questionnaire\n\n• Stage three: The expert feedback was analysed, and changes were incorporated into the questionnaire accordingly.\n\n• Stage four: The pilot-study participants, consisting of the target population, completed the questionnaire and provided feedback to further improve the questionnaire.\n\n• Stage five: Similar to the expert feedback, the feedback from the pilot study was analysed, and changes were incorporated into the questionnaire accordingly.\n\n• Stage six: A final expert panel evaluated the questionnaire.\n\n• Stage seven: The item ratings from the experts were used to validate the overall questionnaire. Following this, item removal took place, and a final validation of the questionnaire was performed.\n\nWhile developing and validating the instrument, the researchers recruited experts to participate in stage two (n=9) and stage six (n=7) of the study. These numbers were recommended by multiple comparable studies as a requirement for the expert panel to establish content validity.22–24 Non-probability purposive- and snowball sampling were used in the selection to identify and select experts appropriately based on the study’s inclusion criteria.25,26 The experts were recruited through social networking, using LinkedIn or ResearchGate, where both were identified as professional or academic social media platforms. To be considered as an expert, participants had to demonstrate expertise in their respective fields where sufficient expertise was defined through one or more of the following: holding academic qualifications at master, doctoral or higher level; being a researcher in a relevant subject field; having relevant publications and/or clinical experience. Here, relevant fields included: KAP studies/instrument development/validation studies, environmental sustainability, the Southern African context and healthcare from either of the following professions: physiotherapy, occupational therapy, speech-language pathology, audiology, human nutrition and dietetics, or nursing. Unlike the mixed-methods study of 2021,21 the profession of human nutrition and dietetics was included in this study as this is a prevalent profession in delivering healthcare.\n\nIn stage four, stratified and snowball sampling were used to select the pilot-study participants.27 The pilot-study participants had to be healthcare professionals in Southern Africa, working in any speciality of their profession, including physiotherapy, occupational therapy, speech-language pathology, audiology, human nutrition and dietetics, and nursing; practising for at least six months or working in academia. Emphasis was placed on recruiting participants from all the above-mentioned professions as well as all Southern African countries were represented among the included pilot-study participants.\n\nThe research team initially aimed to source 18 healthcare professionals as pilot-study participants, specifically two from each Southern African country. After distributing 34 ‘request to participate’ emails and sending numerous ‘follow-up’ emails, the research team received responses from 21 healthcare professionals who were willing to participate. The pilot-study participants were requested to complete the questionnaire and provide feedback. Despite sending reminders via email, only 13 pilot-study participants followed through with this.\n\nDuring the initial expert evaluation (stage two) and the pilot study (stage four), participants were requested to evaluate the entire instrument in terms of layout, instructions, length and/or time taken to complete the questionnaire. The experts were also requested to indicate whether they used a cellphone/mobile phone or laptop/computer to complete the questionnaire such that the research team could identify problems in completing the questionnaire on different common devices. The pilot study participants were divided in half, whereby seven of the pilot-study participants were requested to complete the questionnaire on their laptop/computer and the remaining six were requested to complete the questionnaire on their cell phone/mobile phone. This was done to ensure the accessibility of the questionnaire through various devices. Additionally, the experts also had the opportunity to provide any additional input regarding the content and the format. The pilot study participants were requested to provide overall feedback on the clarity and formulation of the questions.\n\nDuring stages two and six, the experts followed a four-point satisfactory scale in terms of how satisfactory they considered each questionnaire item to be in measuring the construct and/or purpose of the research study: 1) unsatisfactory; 2) somewhat satisfactory, 3) quite satisfactory and 4) highly satisfactory. Additionally, they were requested to provide input as to how each item could be improved or rephrased if they provided a rating of one to three. This feedback was, however, only incorporated during stage three of the study and not in stage six. This data is still available for further questionnaire development.\n\nThe questionnaire was uploaded onto Qualtrics, a web-based tool, for data collection that allows for the creation of questionnaires and the analysis of their results.28 This provided a link sent to participants to enable them to complete the questionnaire.\n\nTo receive feedback from the participants in the different stages, the researchers used Microsoft Word and Google Forms. During stage two, the information was electronically completed in Microsoft Word and tabulated into a Microsoft Excel document in stage three to ensure that the data could be easily accessed and compared. During stages four and six, feedback was requested on Google Forms, which automatically allowed the results to be analysed in Microsoft Excel.\n\nThe pilot study participants provided feedback regarding the clarity and formulation of the questions and the overall content of the questionnaire. The questionnaire was rated by the experts in both stage two and stage six. The item content validity index (I-CVI) refers to the average expert ratings of each questionnaire item. I-CVI ranges from zero to one and expresses a portion of agreement on the relevancy of each item.29 The scale content validity index (S-CVI) was calculated using the average S/CVI (S-CVI/Ave) method, where the sum of all I-CVI scores is divided by the total number of questionnaire items.\n\nIn stage six, the final questionnaire was returned to the experts for a second and final round of feedback. Unfortunately, only seven out of the nine experts were available. In stage seven, following the calculation of both I-CVI and S-CVI/Ave, five questionnaire items were removed as they were rated with an I-CVI of lower than 0,79. One questionnaire item which received a rating of 0,714 was retained following researcher discussions, due to its relevance. The remainder of the questionnaire items all received an I-CVI greater than 0.79 (> 0.79). The final S-SCI/Ave was greater than 0.9 and ensured excellent content validity.29\n\nData analysis occurred in stages three, five and six of the questionnaire development. In stage three, the first round of expert feedback relating to each questionnaire item and the questionnaire as a whole was carefully analysed and discussed by the research team before making changes. In stage five, a similar approach was used in incorporating the feedback from the pilot study. In stage six, the experts rated the questionnaire items according to a four-point satisfactory scale; these ratings were used to determine the questionnaire’s content validity.\n\n\nResults\n\nIn this section, we present our findings according to each stage of the study. Figure 1 provides an overview of the seven stages of the questionnaire development and validation, together with a summary of each stage’s process.\n\nIn this stage, the research team evaluated and reviewed the results of the South African mixed-methods study.21 The KAP questionnaire used in this study consisted of 14 close-ended and 11 open-ended questionnaire items. A total of 203 participants started the questionnaire, but only 100 participants completed the questionnaire, indicating a somewhat poor response rate.21 In hindsight, this was considered as being a potential result of overly difficult knowledge-based questions and having too many open-ended questions. Next to sourcing additional and updated literature, the research team used the questionnaire items from the previous study as a basis for developing their pool of questionnaire items. The qualitative data was used to identify prevalent themes and categories. After this process, 109 potential questionnaire items were availed. To reduce this number and ensure relevance, the research team evaluated each questionnaire item individually. This iterative evaluation process was continued until agreement was reached on the final 29 questionnaire items, excluding the demographic section at the beginning of the questionnaire. Section one consisted of 13 knowledge-based questionnaire items, section two consisted of five attitudinal questionnaire items, and section three included six questionnaire items pertaining to environmental sustainability practices. The barrier and educational sections contained three and two questionnaire items, respectively.\n\nThe nine experts recruited fulfilled various combinations of the expert inclusion criteria. For instance, one of the experts demonstrated expertise in environmental sustainability, the Southern African context and as a healthcare professional. Of the nine experts, seven were healthcare professionals, two demonstrated expertise in KAP study/instrument development/validation studies, four demonstrated expertise in environmental sustainability, and two demonstrated expertise in the Southern African context. Regarding the demographics of the experts, six were female, and three were male, all ranging between the ages of 33 and 61.\n\nThe research team interpreted and analysed the expert ratings and the feedback that was provided. This process was methodical in that each questionnaire item, along with the expert feedback, was discussed individually. Before making the changes to the questionnaire items, the research team reached a consensus for amendments, removal or other measure to be taken for each questionnaire item.\n\nDuring this stage, the I-CVI and S-CVI were calculated on the first draft of the questionnaire to determine a baseline for later comparison. As seen in Table 1, unfortunately, two questions were not evaluated by one of the experts. The S-CVI for section one was calculated at 0.749; for section two at 0.978 for section three at 0.924, section four at 0.963 and section five at 0.944. The S-CVI/ave for the whole questionnaire was 0.860.\n\n* Sum of all questions’ I-CVI divided by the total amount of questions.\n\nFollowing this, the feedback was analysed and then used to change the questionnaire. Regarding the formulation of the instructions, one expert suggested that the phrase ‘based on your own knowledge’ be added to the instructions of the true or false questionnaire items in the knowledge section so that the participants understand that they are not expected to research their responses from a reference source, but to rather use their current knowledge.\n\nMultiple experts noted that questionnaire items 1.1b, 1.1c, 1.1f and 2.1a contained too many theoretical constructs or different terminology, which may conflict with each other and therefore argued that this could confuse participants regarding what aspect of the questionnaire item they should refer to in answering it. For example, questionnaire item 1.1b originally read: ‘The impacts and risks of climate change on mental health are rapidly accelerating’. The expert argued that ‘impacts and risks (are) not necessarily the same thing’. In response to this, the research team confined the questionnaire items listed above to one construct as far as possible, with for this question, the final item reading ‘Climate change has an impact on mental health’.\n\nOne expert indicated that it could not be assumed that all participants completing the questionnaire believe that climate change has man-made origins with catastrophic effects. At the same time, participants can have certain beliefs whilst still being advocates of environmental sustainability. Therefore, the research team added an option to select ‘non-applicable’ in response to certain questionnaire items. Experts suggested that the option of ‘other’ be included for the questionnaire item ‘Climate change has a direct negative impact on human health, through which of the following?’ because some experts recognised additional negative human health impacts of climate change. Another expert noticed that two questionnaire items in the practice section, namely Q3.2 ‘Regardless of whether your place of work has a policy or not, which of the following strategies to improve environmental sustainability in healthcare have been implemented at your place of work?’ and Q3.5 ‘Which of the following environmentally sustainable measures for your place of work would you support?’ each listed different answering options for selection. The expert suggested that the same list of options be provided for both questionnaire items as this would create more flow. Therefore, the options were combined and edited so that they were applicable to both questionnaire items.\n\nFor the questionnaire item ‘What would be your preferred method of being educated on this topic as a practising professional?’ it was suggested to provide the option of ‘Continuous professional development (CPD) activities’ as this could be a means of gaining knowledge on the topic.\n\nThe expert panel further suggested that certain questionnaire items should be rephrased for greater clarity. For instance, it was suggested that the statement ‘environmental sustainability practices should be incorporated into healthcare’ was not specific enough, so the researchers amended this questionnaire item by specifying ‘into healthcare services’. It was also suggested by multiple experts that ‘in your practice’ should be changed to ‘place of work’ to avoid ambiguity of the term ‘practice’, which is often related to ‘private practice’ and thus not applicable for those working in academia or a hospital. Some experts also suggested that a section should be created at the beginning of the questionnaire where definitions for key terms such as climate change and environmental sustainability are provided. The research team decided against this as it would indirectly disclose the answers for the knowledge section in advance and, consequently, participants’ knowledge would be inaccurately represented.\n\nAn expert also noticed that one could not backtrack between the questionnaire items. This expert suggested that for easier navigation and to allow participants to return to previous questionnaire items to provide the option to change their answers, backtracking should be allowed. The research team agreed with this suggestion and activated the backtracking function. A different expert recommended using larger text boxes where participants are allowed to type, such as in the case of selecting the option of ‘other’ for open-ended additions. The questionnaire was adapted accordingly. Although more than one expert proposed the use of Likert scales in more than just the attitudinal section, the research team decided against this recommendation in favour of the aim to derive rich information from participants, which would be limited by using a Likert scale. Minor spelling, numbering and punctuation errors were also highlighted and amended.\n\nSeveral experts also suggested that the questionnaire items be more specific to ensure that participants understand what is being asked. Therefore, additional information was provided in brackets after certain questionnaire items and/or options. As requested, all acronyms were discarded and replaced by full terms.\n\nFinally, all overall feedback was discussed and used to adapt the instrument and make necessary changes to individual questionnaire items. After the changes were incorporated, the questionnaire consisted of 11 knowledge, five attitudes, eight practice, three barriers and two education questionnaire items with a total of 29 questionnaire items.\n\nLiterature pertaining to the design and conduction of KAP questionnaires indicates that a small number of pilot-study participants (five to ten) are recommended as volunteers from the target population.26 In this study, thirteen pilot-study participants provided feedback. They consisted of two participants from Zimbabwe and Lesotho, respectively; three participants from South Africa and Namibia, respectively; and one participant from Angola, Eswatini (Swaziland) and Mozambique, respectively. The pilot-study participants consisted of healthcare professionals in various fields, namely five nurses, four occupational therapists, one physiotherapist, one speech-language pathologist, one audiologist and one professional from human nutrition and dietetics. Six males and seven females between the ages of 24 and 66 participated in the study.\n\nIn the feedback, all of the pilot-study participants stated that the questionnaire was easy to understand and clearly formulated and that they understood what was expected of them when answering the questionnaire items. Of the 13 pilot-study participants, 11 indicated that it did not take them longer than the approximate time stated, that being 15 to 20 minutes, to complete the questionnaire. Therefore, no changes were made to reduce the length of the questionnaire. Four pilot-study participants raised concerns with regard to the terminology used and suggested that simpler words be used to ensure understanding for those less proficient in the English language. Therefore, the research team examined the entire questionnaire and made necessary adjustments to ensure comprehension.\n\nAt this stage, the research team realised that participants from countries that do not have English as an official language, such as Angola and Mozambique, which both have Portuguese as their official language, would have difficulty understanding the questionnaire. Therefore, questions were included in the demographic section, instructing the participants to indicate their first (home) language as well as to rate their proficiency in English according to the provided options of poor, fair, good or excellent. No changes were made to the number of questionnaire items in this stage.\n\nFinal validation and review of the questionnaire was performed by the expert panel. Unfortunately, two experts from the first round of feedback were unavailable for the final round of feedback due to other commitments. Therefore, the final expert panel consisted of seven experts (n=7).\n\nA statistician used the final expert ratings to calculate the Item-Content Validity Index (I-CVI) and the Scale-Content Validity Index (S-CVI). After the final evaluation by the expert panel, four questionnaire items from the knowledge section and one from the practice section, with ratings below 0.79, were removed from the questionnaire. An additional questionnaire item from the educational section also received a rating below 0.79. This questionnaire item required participants to select all methods that they consider applicable: ‘What would be your preferred method of being educated on this topic as a practising professional?’ The research team analysed this questionnaire item, and decided to retain it based on the shared conclusion that it would provide important information which could be used for intervention strategies in future studies.\n\nAs illustrated in Table two below, after calculating the S-CVI/Ave, the developed questionnaire has reached excellent content validity with a rating of 0.922. The S-CVI/Ave for each section was also calculated; the only section with a rating lower than 0.900 was the educational section with a rating of 0.857.\n\nNotably, in the final expert feedback, some questionnaire items received lower S-CVI ratings than in the first round of feedback. Despite this, it was determined by comparing the S-CVI/Ave ratings from the first round of expert feedback (Table 1) to those from the final round of expert feedback (Table 2) that the validity of the questionnaire improved; with an initial S-CVI rating of 0.86 and a final rating of 0.922.\n\n* Sum of all questions’ I-CVI divided by the total amount of questions.\n\n\nDiscussion\n\nThere is limited literature regarding the KAP of healthcare professionals relating to the health impacts of climate change and environmental sustainability in healthcare, and healthcare professionals from the African continent are routinely not included in relevant studies.6,21 In the present study, a 24-item KAP questionnaire regarding environmental sustainability was developed and validated. The S-CVI/avg for the final questionnaire was calculated to be 0,922. An S-CVI of 0,800 is recommended as a minimum rating for a new instrument, and therefore, this study’s questionnaire exceeds the minimum S-CVI standard.29\n\nThe research team could not draw comparisons from other studies because there is limited literature regarding the development and validation of KAP questionnaires pertaining to this topic. A methodologically similar study focussed on developing a questionnaire investigating the KAP among student tuberculosis patients in China. In this study, the questionnaire was distributed to an expert panel consisting of 12 experts who were expected to rate the questionnaire items on a five-point scale (where 0 = very unimportant and 4 = very important). Additionally, a two-round expert consultation was performed and CVI was used as a measure for content validity. This study also met the criteria for a content-valid questionnaire (0.962).30 The similarities between the methodology employed in this and our study, particularly the use of an expert panel and two rounds of expert feedback, were deemed meaningful in that they demonstrated the successful use of the methodological approach.\n\nThe developed questionnaire positively contributes to the area of study as it addresses the recognised gap by availing a validated instrument which measures the KAP of healthcare professionals on environmental sustainability in healthcare in Southern Africa. By way of further contribution, the research team included questionnaire items that are not usually indicated in KAP studies, such as those in the barriers and education sections. This is pertinent because identifying and reducing the barriers that healthcare professionals face has the potential to increase the likelihood of implementation of practices advancing environmental sustainability.6 In addition, data regarding healthcare professionals’ preferred methods on being educated on the topic can be obtained and inform future studies on and implementation of sustainable healthcare education.\n\n\nConclusion\n\nAn instrument to assess the KAP of healthcare professionals in environmental sustainability in Southern Africa was developed and validated in this study. According to expert feedback and statistical calculations, it can be concluded that the questionnaire has an excellent content validity of 0.922 S-CVI/Ave. The questionnaire can therefore be considered as a valid instrument in measuring the KAP of healthcare professionals in environmental sustainability in Southern Africa. The data obtained through questionnaire employment may additionally serve to indicate barriers that prevent healthcare professionals from implementing sustainable practices and their views on sustainable healthcare education. Data collected from this questionnaire can be interpreted and used to develop appropriate and context-specific strategies to adopt more environmentally sustainable healthcare practices.\n\nDespite extensive recruitment, the research team could not obtain any pilot study participants for Botswana and Zambia. Therefore, the questionnaire is not validated for these two Southern African countries. Additionally, two of the nine first round of experts (stage 2) were unavailable to assist in completing the validation of the questionnaire during the second round of expert feedback (stage 6). The research team also considered that some of the pilot-study participants did not have English as their first language and that the comprehension and interpretation of answers could have been misconstrued due to this language barrier.\n\nIt is recommended that the questionnaire be validated in other regions across the world, commencing with the remainder of the countries in Sub-Saharan Africa, to determine its applicability across a wider geographical area. Together with this, it will be important to translate the questionnaire into the respective languages of each target population.\n\nIt is hoped that the questionnaire will be used by researchers from the respective countries in Southern Africa to determine a baseline of information from which various responses aimed at improving environmental sustainability in healthcare can be developed. Additionally, the employment of this can be a means of developing partnerships across Southern African countries - to share ideas, experiences, knowledge, and policies and implement changes.\n\n\nEthical considerations\n\nThe study was conducted in accordance with the Declaration of Helsinki, and the research ethics committee of the University of Pretoria, Faculty of Health Sciences, granted permission to conduct the study (698/2021) on the 7th of February 2022. Informed consent was signed by all of the experts, while pilot-study participants clicked consent on the qualtrics form before proceeding with the questionnaire. Before doing so, both experts and participants had been provided information about the purposes and processes of the study and informed that their personal data would be anonymised. Anonymised data was used in the data analysis and interpretation of the findings. Ethical considerations were adhered to, including upholding confidentiality and anonymity.\n\n\nConsent\n\nWritten informed consent for publication of the participants/patients’ details and/or their images was obtained from the participants/patients/parents/guardians/relatives of the participant/patient.",
"appendix": "Data availability\n\nFigshare: First Round Expert Feedback, Ratings and Question Feedback, 10.6084/m9.figshare.21220283.v2.\n\nThis project contains the following raw underlying data:\n\n• First round expert feedback, ratings and question feedback (this dataset contains the ratings given by 9 experts for every questionnaire item as well as feedback on how each questionnaire item can be improved.) 31\n\nFigshare: First Round Expert Feedback: General Feedback, 10.6084/m9.figshare.21220697.v2.\n\nThis project contains the following raw underlying data:\n\n• First round expert feedback: General feedback (this dataset contains general information provided by the experts about the layout, time taken to complete the questionnaire and additional feedback about the questionnaire.) 32\n\nFigshare: First Round I-CVI and Average S-CVI, 10.6084/m9.figshare.21224900.v2.\n\nThis project contains the following raw underlying data:\n\n• First round I-CVI and average S-CVI (this document shows the item content validity index (I-CVI), as well as the average scale content validity index (S-CVI) calculated after the first round of expert feedback.) 33\n\nFigshare: Pilot Study Participant Feedback, 10.6084/m9.figshare.21224918.v2.\n\nThis project contains the following raw underlying data:\n\n• Pilot study participant feedback (this dataset provides feedback from the pilot-study participants regarding language, clarity of questions, length of the questionnaire and user-friendliness.) 34\n\nFigshare: Final Round Expert Feedback and Ratings, 10.6084/m9.figshare.21224954.v2.\n\nThis project contains the following raw underlying data:\n\n• Final round expert feedback and ratings (this dataset provides the final ratings given by the experts for the improved questionnaire items as well as additional feedback on how the questionnaire can be improved further.) 35\n\nFigshare: Final Round Average I-CVI and S-CVI Calculation, 10.6084/m9.figshare.21224975.v2.\n\nThis project contains the following raw underlying data:\n\n• Final round average I-CVI and S-CVI calculation (the item content validity index (I-CVI) of the questionnaire items included in the final questionnaire as well as the average scale content validity index (S-CVI/Ave) of the final questionnaire.) 36\n\nData is available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0).\n\nFinal questionnaire on the knowledge, attitudes and practices of healthcare professionals on environmental sustainability in Southern Africa, 10.6084/m9.figshare.21224993.v2\n\nThis project contains the following raw underlying data:\n\n• Final questionnaire on the knowledge, attitudes and practices of healthcare professionals on environmental sustainability in Southern Africa (the final questionnaire of 24 questionnaire items with excellent content validity.) 37\n\nData is available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0).\n\n\nAcknowledgements\n\nThe research team would like to express its gratitude to the group of experts and pilot-study participants who dedicated their time to assist with the study.\n\n\nReferences\n\nAnabaraonye B, Ewa BO, Wala K: The Impacts of Climate Change on Nigeria’s Health Sector and Innovative Solutions for Environmental Sustainability.2020; 2: 1–7.\n\nMcMichael AJ, Friel S, Nyong A, et al.: Global environmental change and health: impacts, inequalities, and the health sector. BMJ. 2008 Jan 26; 336(7637): 191–194. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRomanello M, Di Napoli C, Drummond P, et al.: The 2022 report of the Lancet Countdown on health and climate change: health at the mercy of fossil fuels. Lancet. 2022 Nov 5; 400(10363): 1619–1654. PubMed Abstract | Publisher Full Text\n\nWorld Health Organisation: 2021 WHO health and climate change global survey report. Geneva: World Health Organization; 2021.\n\nFrumkin H, Haines A: Global Environmental Change and Noncommunicable Disease Risks. Annu. Rev. Public Health. 2019 Apr 1; 40(1): 261–282. Publisher Full Text\n\nKotcher J, Maibach E, Miller J, et al.: Views of health professionals on climate change and health: a multinational survey study. Lancet Planet Health. 2021 May; 5(5): e316–e323. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKarliner J, Slotterback S, Boyd R, et al.: Health care’s climate footprint: the health sector contribution and opportunities for action. Eur. J. Pub. Health. 2020; 30(Supplement_5). Publisher Full Text\n\nRowan NJ, Laffey JG: Unlocking the surge in demand for personal and protective equipment (PPE) and improvised face coverings arising from coronavirus disease (COVID-19) pandemic – Implications for efficacy, re-use and sustainable waste management. Sci. Total Environ. 2021 Jan; 752: 142259. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLenzen M, Malik A, Li M, et al.: The environmental footprint of health care: a global assessment. Lancet Planet Health. 2020 Jul; 4(7): e271–e279. Publisher Full Text\n\nYang L, Liu C, Hess J, et al.: Health professionals in a changing climate: protocol for a scoping review. BMJ Open. 2019 Feb 1; 9(2): e024451. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWorld Health Organisation: COP26 special report on climate change and health: the health argument for climate action. Geneva: World Health Organization; 2021.\n\nHubbert B, Ahmed M, Kotcher J, et al.: Recruiting health professionals as sustainability advocates. Lancet Planet Health. 2020 Oct; 4(10): e445–e446. PubMed Abstract | Publisher Full Text\n\nAhmad S, Eckelman MJ, Sherman J: Environmental Impacts of the U.S. Health Care System and Effects on Public Health. PLoS One. 2016 Jun 9; 11(6): e0157014. Publisher Full Text\n\nHowes M, Wortley L, Potts R, et al.: Environmental Sustainability: A Case of Policy Implementation Failure?2017; 18.\n\nTrewin B, Adam JP, Beltran J, et al.: State of the Climate in Africa.2019.\n\nZiervogel G, New M, Archer van Garderen E, et al.: Climate change impacts and adaptation in South Africa: Climate change impacts in South Africa. Wiley Interdiscip. Rev. Clim. Chang. 2014 Sep; 5(5): 605–620. Publisher Full Text\n\nMeadows ME: Global Change and Southern Africa. Geogr. Res. 2006 Jun; 44(2): 135–145. Publisher Full Text\n\nAndrade C, Menon V, Ameen S, et al.: Designing and Conducting Knowledge, Attitude, and Practice Surveys in Psychiatry: Practical Guidance. Indian J. Psychol. Med. 2020 Sep; 42(5): 478–481. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTorres-Vallejo Y, Ruiz-Galeano CA, Bonilla-Escobar FJ: Recommendations for Future Articles on Knowledge, Attitudes and Practices in IJMS. Int. J. Med. Stud. 2013 Dec 31; 1(3): 135–136. Publisher Full Text\n\nMuleme J, Kankya C, Ssempebwa JC, et al.: A Framework for Integrating Qualitative and Quantitative Data in Knowledge, Attitude, and Practice Studies: A Case Study of Pesticide Usage in Eastern Uganda. Front. Public Health. 2017 Dec 8; 5: 15. Publisher Full Text\n\nLister HE, Mostert K, Botha T, et al.: South African Healthcare Professionals’ Knowledge, Attitudes, and Practices Regarding Environmental Sustainability in Healthcare: A Mixed-Methods Study. Int. J. Environ. Res. Public Health. 2022 Aug 16; 19(16): 10121. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMallah N, Rodriguez-cano R, Figueiras, et al.: Design, reliability and construct validity of a Knowledge, Attitude and Practice questionnaire on personal use of antibiotics in Spain. Sci. Rep. 2020; 10: 20668. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAndrade C, Menon V, Ameen S, et al.: Designing and Conducting Knowledge, Attitude, and Practice Surveys in Psychiatry: Practical Guidance. Indian J. Psychol. Med. 2020; 42(5): 4.\n\nSaefi M, Fauzi A, Kristiana E, et al.: Validating of Knowledge, Attitudes, and Practices Questionnaire for Prevention of COVID-19 infections among Undergraduate Students: A RASCH and Factor Analysis. Eurasia J. Math., Sci Tech. Ed. 2020; 16(12): em1926. Publisher Full Text\n\nEtikan I, Musa S, Alkassim R: Comparison of Convenience Sampling and Purposive Sampling. Am. J. Theor. Appl. Stat. 2016; 5(1): 1. Publisher Full Text\n\nNaderifar M, Goli H, Ghaljaie F: Snowball Sampling: A Purposeful Method of Sampling in Qualitative Research. Strides Dev. Med. Educ. 2017 Sep 30; 14(3). Publisher Full Text Reference Source\n\nAcharya AS, Prakash A, Saxena P, et al.: Sampling: why and how of it? Indian J. Med. Spec. 2013 Jul 7; 4(4): 330–333. Publisher Full Text\n\nCushman JE, Faulkner R, Fusso-Rollins M, et al.: Resource Review—Using Qualtrics Core XM for Surveying Youth.2021.\n\nRodrigues IB, Adachi JD, Beattie KA, et al.: Development and validation of a new tool to measure the facilitators, barriers and preferences to exercise in people with osteoporosis. BMC Musculoskelet. Disord. 2017 Dec; 18(1): 540. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFan Y, Jiang H, Li Y, et al.: Development and psychometric testing of the Knowledge, Attitudes and Practices (KAP) questionnaire among student Tuberculosis (TB) Patients (STBP-KAPQ) in China. BMC Infect. Dis. 2018; 18: 213. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLister H, Mostert K, Botha T, et al.: First round expert feedback, ratings and question feedback. figshare. 2022 [cited 2024 Oct 3]. Reference Source\n\nLister H, Mostert K, Botha T, et al.: First round expert feedback: General feedback. figshare. 2022 [cited 2024 Oct 3]. Reference Source\n\nLister H, Mostert K, Botha T, et al.: First round I-CVI and average S-CVI. figshare. 2022 [cited 2024 Oct 3]. Reference Source\n\nLister H, Mostert K, Botha T, et al.: Pilot study participant feedback. figshare. 2022 [cited 2024 Oct 3]. Reference Source\n\nLister H, Mostert K, Botha T, et al.: Final round expert feedback and ratings. figshare. 2022 [cited 2024 Oct 3]. Reference Source\n\nLister H, Mostert K, Botha T, et al.: Final round average I-CVI and S-CVI calculation. figshare. 2022 [cited 2024 Oct 3]. Reference Source\n\nLister H, Mostert K, Botha T, et al.: Final questionnaire on the knowledge, attitudes and practices of healthcare professionals on environmental sustainability in Southern Africa. figshare. 2022 [cited 2024 Oct 3]. Reference Source"
}
|
[
{
"id": "355678",
"date": "28 Jan 2025",
"name": "Ebenezer Akore Yeboah",
"expertise": [
"Reviewer Expertise Nursing",
"Climate change",
"sustainability"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nSummary: Environmental sustainability in healthcare is quite a significant area needed to be explored to help protect and maintain the planet for all forms of life. Most commonly, research in this area is lacking in the global south especially Africa, hence it is significant to have seen and reviewed this paper on developing an instrument within African context.\n\nMy Review & Questions Well done to the authors. 1. Please check the third sentence in the third paragraph in the background for grammatical corrections. 2. You indicated the medium of selection for the expert reviewers... Please what was the medium of participant selection for the pilot study? 3. Under developing a questionnaire and item clarity in the methods section, you indicated below; \"This feedback was, however, only incorporated during stage three of the study and not in stage six. This data is still available for further questionnaire development\". Question; Were the feedback significant, if yes why not incorporated, if no why have you alluded to the need for that feedback in further development? 4. At what stage of your process did you undertake a face validity of the instrument that is if it was performed, if no face validity why? 5. In the questionnaire, 1a. climate change has a direct negative influence on human health 1b. Climate change has an impact on mental health… Question: Is mental health not a subset of human health? Why have you emphasised mental health, or does 1a refer to human physical health? I would appreciate a response to this. 6. The word ‘Poverty stricken countries’ is too harsh. A country's presence in the global south can make them vulnerable but they may not be poverty-stricken… Could you use a term like ‘low-income countries’ or 'countries with low adaptation plans' or global south countries or any other term which is friendly?\n\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?\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/13-1308
|
https://f1000research.com/articles/13-1305/v1
|
31 Oct 24
|
{
"type": "Case Study",
"title": "A libraries reproducibility hackathon: connecting students to University research and testing the longevity of published code",
"authors": [
"Chasz Griego",
"Kristen Scotti",
"Elizabeth Terveen",
"Joseph Chan",
"Daisy Sheng",
"Alfredo González-Espinoza",
"Christopher Warren",
"Kristen Scotti",
"Elizabeth Terveen",
"Joseph Chan",
"Daisy Sheng",
"Alfredo González-Espinoza",
"Christopher Warren"
],
"abstract": "Reproducibility is a basis of scientific integrity, yet it remains a significant challenge across disciplines in computational science. This reproducibility crisis is now being met with an Open Science movement, which has risen to prominence within the scientific community and academic libraries especially. To address the need for reproducible computational research and promote Open Science within the community, members of the Open Science and Data Collaborations Program at Carnegie Mellon University Libraries organized a single-day hackathon centered around reproducibility. Partnering with a faculty researcher in English and Digital Humanities, this event allowed several students an opportunity to interact with real research outputs, test the reproducibility of data analyses with code, and offer feedback for improvements. With Python code and data shared by the researcher in an open repository, we revealed that students could successfully reproduce most of the data visualizations, but they required completing some manual setup and modifications to address depreciated libraries to successfully rerun the code. During the event, we also investigated the option of using ChatGPT to debug and troubleshoot rerunning this code. By interacting with a ChatGPT API in the code, we found and addressed the same roadblocks and successfully reproduced the same figures as the participating students. Assessing a second option, we also collaborated with the researcher to publish a compute capsule in Code Ocean. This option presented an alternative to manual setup and modifications, an accessible option for more limited devices like tablets, and a simple solution for outside researchers to modify or build on existing research code.",
"keywords": [
"Reproducibility",
"Hackathon",
"Academic Libraries",
"Open Science",
"Metascience",
"Digital Humanities",
"Computational Research",
"Software",
"Community Engagement"
],
"content": "Introduction\n\nReproducibility in scientific research is a highly regarded concept that measures both the credibility and soundness of rigorous studies.1,2 In the context of research, the term reproducibility is often loosely defined or used interchangeably with replicability. The National Academy of Sciences convened in 2019 to develop a definition3 and differentiate between reproducibility, replicability, and generalizability.2,3 Reproducibility, which is generally consistent with computational reproducibility, is defined as consistent computational outcomes by utilizing identical input data, procedures, methods, code, and analytical conditions. Replicability is defined as uniform outcomes across research projects designed to address the same scientific question, where each project collects its own data. And finally, generalizability is defined as how well findings of a study can be applied to different contexts or populations beyond the original.\n\nModern research continues to face multiple challenges surrounding reproducibility. The adoptable skills and practices that promote reproducibility may vary between fields,4–6 awareness or guidance is often lacking,4,6,7 and the time and resources devoted to teaching and practicing reproducibility may be deficient.8 Computation research, in particular, faces barriers to reproducibility with software inconsistencies, changing versions and dependencies,9 and insufficient documentation of datasets10 or methods.11 For example, Liu and Salganik10 found that the complexity of employed computational methods impacts reproducibility. The more common methods in a given field may ease reproducibility, as they are familiar and well-documented, but more advanced methods can pose greater challenges, requiring specialized knowledge, environments, and resources that are not as readily available or standardized.\n\nInvesting in tools and practices around computational reproducibility enhances the transparency and reliability of scientific findings by enabling independent verification of results and fostering further research on established findings. Such a shift in computational research practice is important since it increases research credibility and efficiency and avoids wasted efforts in attempting to build on unreliable results.12,13 The scientific community is increasingly advocating for the use of various tools and practices aimed at improving reproducibility of computational research,11,14 including adopting open-source software,11 conducting version control (e.g., Git and GitHub),15 encapsulating computing environments (eg. Docker),11,16,17 and following community-driven standards and frameworks.\n\nIn general, scientific communities are upping advocacy through the Open Science movement. Open Science promotes transparency of research process, data, methodologies, and outputs; enhancing accessibility and usability by the broader scientific community.18,19 Reproducibility is fundamental to open science,18,20 by ensuring verifiable scientific claims to the community; made possible via open sharing of datasets, methodology, code, and using open source software. Overall, alignment with reproducible practices moves the scientific community towards a more collaborative environment.19\n\nAt the Carnegie Mellon University Libraries, a dedicated Open Science & Data Collaborations Program (OSDC) was established in 2018, which highlights the Libraries’ resources and tools that foster open, transparent, and reproducible research.21 In this program, librarians and functional specialists serve as advocates, consultants, and collaborators for researchers accessing the existing Open Science infrastructure in the Libraries, including CMU’s institutional repository, KiltHub,22 and research data management services.23 In addition, the Libraries have held multiple iterations of the Open Science Symposium,24 which gathered global researchers and thought leaders in academia, industry, and publishing to discuss the ways that Open Science has transformed research. The OSDC program also created roles for STEM PhDs to transition into Open Science and librarianship through an Open Science Postdoctoral Associate position, with Chasz Griego and Kristen Scotti being the first and second candidates in this role, respectively. Through this postdoctoral role, Griego considered ways to explore reproducibility integration and evaluation among researchers and students at CMU.25\n\nMotivated by the challenges surrounding reproducibility and the growing awareness of Open Science, members of the CMU Libraries and OSDC Program organized a single-day hackathon centered around reproducibility. Hackathons, which are time-bound events for groups to collectively solve or explore a technical problem, often find libraries as a suitable host as a neutral and welcoming space on campus that harbors learning, discovery, and collaboration.26 The CMU Libraries has effectively hosted multiple hackathons, including Biohackathons and a recent AI Literacy Resource Hackathon.27–29 Libraries and hackathons surrounding reproducibility is also not a novel concept. The Center for Digital Scholarship at Leiden University held ReprohackNL in 2019, where participants attempted to reproduce published results using authors’ provided data and code in a single day event.30\n\nAt this hackathon event, the organizers observed how participants faced challenges with insufficient documentation, data behind a paywall, and problems with code and proprietary software. The CMU Libraries Reproducibility Hackathon aimed to offer a similar model, but here, we focused on the reproducibility of a study with shared data and code around a subject that could create interdisciplinary collaboration across students and researchers at CMU.\n\n\nPurpose of the event\n\nThe CMU Libraries Reproducibility Hackathon was an event that allowed any participant the opportunity to reproduce research results produced by a university professor. The purpose of such an event is to increase awareness of reproducibility as a realistic piece of the research life cycle, and demonstrate the outcomes of research scrutiny, which could theoretically be done by anyone. Most are familiar with the concept of reproducibility at a surface level, but many may not actually have a grasp on what that may look like, how it may happen, or how impactful it could be for any study. In an extremely idealistic world, a person with any background, experience, or research interest would have access to every material behind a particular study. These materials, again in an ideal case, would include all resources and guidance for a person to reproduce each result, assuring the findings first-hand. In reality, most research is very distanced from such an idealistic scenario, however, an event like a reproducibility hackathon can actually attempt to measure this distance for researchers willing to participate. For this hackathon, we offered one academic researcher the opportunity to put their research outputs up to scrutiny. Regardless of the outcome, a volunteer researcher helps set an example. If the results are highly reproducible, this presents a recognizable feat, and if the results prove more difficult to reproduce, this presents an opportunity to reflect on ways to improve. Work that is less reproducible does not have to be met with shame or guilt, but a humbling opportunity to learn and do better.\n\nFor the CMU Libraries Reproducibility Hackathon, we teamed up with Christopher Warren, a Professor of English and Associate Department Head in the Dietrich College of Humanities and Social Sciences at CMU. As the subject for a reproducibility assessment, Warren offered the content of a published data analysis of the Oxford Dictionary of National Biography (ODNB),31,32 a collection of biographies for over 60,000 influential figures in British history. Warren’s work is credited as an “audit” of the ODNB,33 revealing the biases and assumptions hidden beneath the vastness of big data infrastructure. This subject was well aligned with the event, because with an analysis such as Warren’s, which scrutinizes the soundness of a massive data collection, the Python code that reveals the findings must also hold up to its own audit, ensuring that changing versions and dependencies do not prevent repeat analyses. With Warren offering his humanities research as an exemplary case, we offer further dialog around inclusivity of all research areas beyond STEM in the Open Science movement.34\n\n\nEvent execution\n\nWe openly distributed a call for participants to anyone interested from CMU and other institutions in the greater Pittsburgh area. The call noted that knowledge and awareness of scientific programming with Python and/or R was a desired, but not required, condition for participation. Participants submitted their interest and background through a short form and had the option to attend one of two information sessions a week prior to the event. During the information session, participants received a link to Warren’s manuscript to provide sufficient time to read into the details of the work. They were asked to not search for any items related to the work, avoiding the risk of early access to data and code posted to a repository.\n\nThe hackathon was scheduled for just one day, with participants and organizers convening in a library space during typical business hours (9am - 5pm). A project page on Open Science Framework (OSF)35 was created for the event, where participants could access event information and guidance, a copy of Warren’s manuscript, and documents with links to access data and code. In addition to the published manuscript, Warren deposited supplementary research outputs to Harvard Dataverse, which includes a Jupyter Notebook, CSV files, Open Refine transformation JSON files, and others.32 This collection of outputs served as one option for participants to use to attempt to reproduce the study. This option is arguably open, having research outputs deposited in a repository to ensure secure storage, public access, and findability with a DOI, and this option used non-proprietary file formats such as CSV and JSON, and open-source Python code written in notebooks. Such attributes greatly promote reusability once users download each output and ensure that Python and all necessary libraries are installed.\n\nWe also provided a second option that aims to greatly facilitate reproducible computational research. The same data and code found in Harvard Dataverse were organized and configured in a Code Ocean capsule.36 Code Ocean is a platform that allows researchers to archive research data and code along with preserved language and library versions plus dependencies and a metadata record in a self-contained capsule. Capsules are discoverable with a DOI, and outside users can perform reproducible runs that compile and execute code in a virtual environment, producing results that match the original analysis.\n\n\nObservations and reflections\n\nIn the following, we summarize the experiences of participants in the reproducibility hackathon. Some notes are also listed briefly in Table 1. One participant, Elizabeth Terveen, chose the option of downloading the materials from Harvard Dataverse and attempting to run the Jupyter Notebook in a new Python environment working with the Anaconda package manager. To run the code, Terveen had to install four Python libraries (Pandas, Nltk, Matplotlib, and Plotly). One of the existing import statements in the notebook, regarding Plotly, returned an error due to a module depreciation.\n\nOf the figures produced in the notebook, fourteen figures were successfully reproduced by Terveen, with six of these figures requiring some troubleshooting. This included supplying values for arguments in functions that were not specified in the original code, but a resulting error stated as required. The name of a keyword argument related to a Matplotlib function had also become depreciated, which required an update to the original code. Eight figures were not successfully reproduced because of file paths in the code that were not consistent with directory structure Terveen had after downloading from the repository.\n\nA second participant, Joseph Chan, also chose the option to download the materials from Harvard Dataverse. Chan immediately noted that if a “requirements.txt” file was included with the original deposit, any user trying to reproduce the results would be able to download and install the appropriate packages and versions. Based on Chan’s setup, five python libraries and Jupyter needed to be installed, including Pandas, Nltk, Pickle, Numpy, and Matplotlib. Additionally, a plotting library was deprecated, requiring an import statement to be updated. Once again, keyword arguments were depreciated and had to be updated. Two figures did not display upon running and were unable to be solved.\n\nChan also created a modified version of the research outputs as a zip file uploaded to OSF (https://osf.io/hvbzm), which contains a requirements.txt file, all necessary data, and all the code from the notebook in a single Python (.py) file. With this, users can simply reproduce the work by executing a shell script from a terminal. Copies of figures that were successfully reproduced were uploaded to OSF (https://osf.io/gqk8e/), with titles altered with either a note or a name to verify that the figures were original copies (see Figure 1 for examples).\n\nOverall, this process of reproducing results using files downloaded from a repository produced several challenges with requirements to install packages, understand depreciations for some packages, and troubleshooting changes in syntax from evolving versions of software. Though there was trial and error, participants were able to successfully reproduce figures from this study. Additionally, participants provided their own insight to develop an updated collection of research outputs that help others reproduce this work more easily.\n\n\nAdditional outcomes and lessons learned\n\nAlfredo González-Espinoza, our colleague who participated in the assessment as well, offered an interesting anecdote while pursuing reproducibility via both Harvard Dataverse and Code Ocean (https://osf.io/brn6d). In order to run the code downloaded from the repository, he had to install Python, Jupyter, all required libraries, and found the same depreciation errors as other participants; however, he was successful with reproducibility via the Code Ocean capsule. González-Espinoza’s scenario was interesting because he used a gaming laptop to reproduce from the repository, which doesn’t make a difference when the issue is installing software, but for the capsule he accessed the code via an old Chromebook tablet. This individual experience calls to attention the fact that a platform like Code Ocean may promote accessibility for people that may have limited access to computers, and instead only have access to devices that one can’t use to download and install software as easily.\n\nThe hackathon offered an additional opportunity for exploration. Kristen Scotti investigated ways to troubleshoot reproducing the output of the code using generative AI. Python, like many other programming languages, undergoes frequent updates, deprecating functions or changing syntax overtime, making author-provided code more difficult to work with or potentially incompatible with newer versions. Here, Scotti ran the author-provided code through ChatGPT to request updates (https://osf.io/r65ev). ChatGPT’s programming capabilities include the ability to interpret, debug, and suggest updates to code.37 ChatGPT updated code successfully for all recreated plots except one, which also provided issues for other participants. The likely culprit was formatting issues due to syntax changes and complexity of the provided code block. A more effective approach might be to ask ChatGPT to convert the code in smaller sections, though this often requires someone experienced in the language to fine-tune both the prompts and the outputs.\n\nOutside the hackathon setting, we revisited the capsule version of Warren’s research to test how easily his work could be adapted within this platform. For instance, figures 28 and 29 in the manuscript have prompted discussion in other sources.33,38 Figure 29, in particular, displays the historical significance of selected women in the ODNB, and the span of living years of these women from 1830-2000 (listed here in Figure 2b). However, horizontal bars representing a span of years could instead incidentally suggest the number of women belonging to the corresponding historical significance. We addressed this ambiguity by creating a new version of the capsule on Code Ocean39 where additional cells in the Jupyter Notebook create new versions of these figures which explicitly state the numbers of years each vertical bar spans (Figure 2a).\n\n\nDiscussion and conclusions\n\nWe have outlined the execution and outcomes of a Reproducibility Hackathon, hosted by CMU Libraries, that focused on the reusability of data and code shared by a faculty member from the university. This event allowed students to interact with real research outputs to learn potentially new skills and fields of study while simultaneously offering their perspective. In reviewing the reproducibility of research code from the participating faculty member, Christopher Warren, students showed that manual setup was needed to rerun research code, and along with that, depreciations required them to write updates and modifications. One participating student sought a way to encapsulate the code so that everything was packaged and shareable, enabling an outside user to properly reproduce the run by executing a single script. Lastly, we attempted to rerun the code while using a ChatGPT API to debug. This option identified and addressed the same errors that student participants met and successfully reproduced the same figures.\n\nCode Ocean presented an alternative to sharing code without manual installations or depreciations. An alternative of Warren’s outputs were assembled and published in a reproducible capsule on Code Ocean. This option presented itself as a more accessible way for a user to interact with computational research, as a participating colleague revealed the ease of interacting with the capsule on a tablet device. Finally, we adapted Warren’s code in Code Ocean to produce an alternative depiction of data visualizations presented in the original work. Doing this offered an example of how a reproducibility-centered platform can promote research as ongoing conversation that openly invites community members to offer constructive insights.\n\nA reproducibility hackathon at an academic institution creates an open environment for researchers to put their published work to the test, opening themselves to constructive feedback around reproducibility, and allowing students or other researchers to interact with real research artifacts. We presented our experience here to offer a blueprint for other academic libraries to execute similar events, boost awareness of the threats to preserving research code, and highlight how new platforms eliminate these threats to reproducibility and enhance adaptation along the research lifecycle.\n\n\nEthics and consent\n\nEthical approval and consent were not required.\n\n\nAuthor contributions\n\nChasz G: Conceptualization, Data Curation, Formal Analysis, Methodology, Project Administration, Resources, Software, Supervision, Validation, Writing – Original Draft Preparation; Kristen S: Conceptualization, Data Curation, Formal Analysis, Resources, Software, Validation, Visualization, Writing – Original Draft Preparation; Elizabeth T: Data Curation, Formal Analysis, Validation, Visualization; Joseph C: Data Curation, Formal Analysis, Software, Validation; Daisy S: Data Curation, Visualization; Alfredo G-E: Data Curation, Formal Analysis, Validation; Christopher W: Conceptualization, Data Curation, Resources, Software, Visualization, Writing – Review & Editing",
"appendix": "Data availability\n\nOpen Science Framework: Reproducibility Hackathon 2024. https://doi.org/10.17605/OSF.IO/AQ69R. 35\n\nThe project contains the following underlying data:\n\n• All original documents and materials prepared and produced from the event.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nHarvard Dataverse: Replication Data for: Historiography’s Two Voices: Data Infrastructure and History at Scale in the Oxford Dictionary of National Biography (ODNB). https://doi.org/10.7910/DVN/D3KFLP. 32\n\nThe project contains the following underlying data:\n\n• All data and code supporting the original work that was the focus of the hackathon.\n\nData are available under the terms of the Creative Commons 1.0 Universal Dead (CC0 1.0)\n\nCode Ocean: Replication Data for: Historiography’s Two Voices: Data Infrastructure and History at Scale in the Oxford Dictionary of National Biography (ODNB) (Version 1). https://doi.org/10.24433/CO.6313661.v1. 36\n\nThe project contains the following underlying data:\n\n• All data, code, and software environment details supporting the original work that was the focus of the hackathon.\n\nData and code are available under the terms of the Creative Commons CC0 licenses with no rights reserved.\n\nCode Ocean: Replication Data for: Historiography’s Two Voices: Data Infrastructure and History at Scale in the Oxford Dictionary of National Biography (ODNB) (Version 2). https://doi.org/10.24433/CO.6313661.v2. 39\n\nThe project contains the following underlying data:\n\n• All data, code, and software environment details supporting the original work that was the focus of the hackathon as well as appended code that adapts Figures 28 and 29 from the original study.\n\nData and code are available under the terms of the Creative Commons CC0 1.0 licenses with no rights reserved.\n\n\nAcknowledgements\n\nWe thank Melanie Gainey and Tom Hughes from the CMU Libraries for useful discussions about hackathons and their support during the event.\n\n\nReferences\n\nBuckheit JB, Donoho DL: WaveLab and Reproducible Research.Antoniadis A, Oppenheim G, editors. Wavelets Stat. New York, NY: Springer; 1995; pp. 55–81. Publisher Full Text\n\nBarba LA: Terminologies for reproducible research. ArXiv Prepr. ArXiv180203311. 2018.\n\nReproducibility and Replicability in Science. Natl. Acad. Sci. 2019. Reference Source\n\nBaker M, Baker M: 1,500 scientists lift the lid on reproducibility. Nature. 2016; 533: 452–454. Publisher Full Text\n\nMullane K, Williams M: Enhancing reproducibility: Failures from Reproducibility Initiatives underline core challenges. Biochem. Pharmacol. 2017; 138: 7–18. PubMed Abstract | Publisher Full Text\n\nKohrs FE, Auer S, Bannach-Brown A, et al.: Eleven strategies for making reproducible research and open science training the norm at research institutions. elife. 2023; 12: e89736. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRich-Edwards JW, Maney DL: Best practices to promote rigor and reproducibility in the era of sex-inclusive research. elife. 2023; 12: e90623. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSix factors affecting reproducibility in life science research and how to handle them.n.d. (accessed May 28, 2024). Reference Source\n\nImplementing Reproducible Research. Routledge CRC Press; n.d. (accessed May 28, 2024). Reference Source\n\nLiu DM, Salganik MJ: Successes and struggles with computational reproducibility: lessons from the fragile families challenge. Socius. 2019; 5: 2378023119849803. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPiccolo SR, Frampton MB: Tools and techniques for computational reproducibility. Gigascience. 2016; 5: s13742–s13016. Publisher Full Text\n\nIoannidis JPA: Why Most Published Research Findings Are False. PLoS Med. 2005; 2: e124. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeng RD: Reproducible Research in Computational Science. Science. 2011; 334: 1226–1227. Publisher Full Text\n\nBrito JJ, Li J, Moore JH, et al.: Recommendations to enhance rigor and reproducibility in biomedical research. GigaScience. 2020; 9: giaa056. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRam K: Git can facilitate greater reproducibility and increased transparency in science, Source Code. Biol. Med. 2013; 8: 1–8. Publisher Full Text\n\nBoettiger C: An introduction to Docker for reproducible research. ACM SIGOPS Oper. Syst. Rev. 2015; 49: 71–79. Publisher Full Text\n\nCheifet B: Promoting reproducibility with Code Ocean. Genome Biol. 2021; 22: 65. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMunafò MR, Nosek BA, Bishop DVM, et al.: A manifesto for reproducible science. Nat. Hum. Behav. 2017; 1: 0021–0021. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcKiernan EC, Bourne PE, Brown CT, et al.: How open science helps researchers succeed. elife. 2016; 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMunafò M: Open science and research reproducibility. Ecancermedicalscience. 2016; 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang H, Gainey M, Campbell P, et al.: Implementation and assessment of an end-to-end Open Science & Data Collaborations program. F1000 Res. 2022; 11: 501. PubMed Abstract | Publisher Full Text | Free Full Text\n\nScherer D, Valen D: Balancing Multiple Roles of Repositories. Developing a Comprehensive Repository at Carnegie Mellon University, Publications; 2019; vol. 7. ; p. 30. Publisher Full Text\n\nVan Tuyl SI: Developing a research data management services infrastructure at. Carnegie Mellon University, Carnegie Mellon University; 2013.\n\nWang H, Gainey M, Van Gulick A: Carnegie Mellon’s first Open Science Symposium - Themes about research data and their reuse.2019. (accessed April 1, 2024). Reference Source\n\nGriego C: Integrating and Evaluating Best Practices in Research Reproducibility. Carnegie Mellon University; 2023. (accessed March 9, 2024). Reference Source\n\nLongmeier MM: Hackathons and libraries: the evolving landscape 2014-2020.2021.\n\nBongiovanni E, Slayton E, Agate N, et al.: AI Literacy Resource Hackathon. Open Sci. Framew. 2024. Publisher Full Text\n\nAl Khleifat A, Smith J, Blobner B, et al.: SnpReportR: A Tool for Clinical Reporting of RNAseq Expression and Variants, BioHackrXiv.2021.\n\nKubica J, Kumar R, Tan G, et al.: The fourth annual Carnegie Mellon Libraries hackathon for biomedical data management, knowledge graphs, and deep learning, BioHackrXiv.2023.\n\nHettne KM, Proppert R, Nab L, et al.: ReprohackNL 2019: how libraries can promote research reproducibility through community engagement. IASSIST Q. 2020; 44: 1–10. Publisher Full Text\n\nWarren CN: Historiography’s Two Voices: Data Infrastructure and History at Scale in the Oxford Dictionary of National Biography (ODNB). J. Cult. Anal. 2018; 3. Publisher Full Text\n\nWarren C: Replication Data for: Historiography’s Two Voices: Data Infrastructure and History at Scale in the Oxford Dictionary of National Biography (ODNB).2018. Publisher Full Text\n\nGuldi J: The Dangerous Art of Text Mining: A Methodology for Digital History. Cambridge: Cambridge University Press; 2023. Publisher Full Text\n\nLongley Arthur P, Hearn L: Toward open research: A narrative review of the challenges and opportunities for open humanities. J. Commun. 2021; 71: 827–853.\n\nGriego C, Warren CN, Scotti K, et al.: Reproducibility Hackathon.2024; 2024. (accessed April 23, 2024). Reference Source\n\nWarren C: Replication Data for: Historiography’s Two Voices: Data Infrastructure and History at Scale in the Oxford Dictionary of National Biography (ODNB).2024. Publisher Full Text\n\nBiswas S: Role of ChatGPT in Computer Programming.: ChatGPT in Computer Programming., Mesopotamian. J. Comput. Sci. 2023; 2023: 8–16.\n\nGuldi J: From Critique to Audit: A Pragmatic Response to the Climate Emergency from the Humanities and Social Sciences, and a Call to Action. KNOW J. Form. Knowl. 2021; 5: 169–196. Publisher Full Text\n\nWarren C, Scotti K: Replication Data for: Historiography’s Two Voices: Data Infrastructure and History at Scale in the Oxford Dictionary of National Biography (ODNB).2024. Publisher Full Text"
}
|
[
{
"id": "339316",
"date": "04 Dec 2024",
"name": "Benjamin Antunes",
"expertise": [
"Reviewer Expertise My research area if reproducible research in high performance computing. This paper could benefit from having broader information about reproducibility tools",
"however",
"it is a short paper describing a Hackathon."
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper presents a reproducibility hackathon where students attempted to replicate the work of Professor Christopher Warren. In my opinion, this is an excellent initiative. Education is a critical avenue for improving reproducibility, as it raises awareness among students and future researchers about its importance.\nThe paper is not highly technical; instead, it provides an overview of the types of challenges encountered when attempting to reproduce results. It highlights the use of literate programming and ChatGPT to facilitate code reproduction and illustrates common difficulties, such as handling software dependencies and library versioning in Python. The hackathon focused on research in the field of Digital Humanities.\nMy Remarks: Introduction – First Paragraph: As noted by Barba (2018), computer science was one of the only field to use swaped definitions between reproducibility and replicability (reproducibility is doing the same experiment to obtain the same results, while replicability is doing another experiment to obtain the same scientific conclusion). ACM recently adopted the NISO-recommended terminology for computer science:\n\"*As a result of discussions with the National Information Standards Organization (NISO), it was recommended that ACM harmonize its terminology and definitions with those used in the broader scientific research community, and ACM agreed with NISO’s recommendation to swap the terms “reproducibility” and “replication” with the existing definitions used by ACM as part of its artifact review and badging initiative. ACM took action to update all prior badging to ensure consistency.\" https://www.acm.org/publications/policies/artifact-review-and-badging-current\nThis shift swaped the definition of reproducibility and replicability. However, from an epistemological standpoint, reproducibility remains the broader, general term. The paper omits a crucial concept in computer science: repeatability (bitwise repeatability), which is indispensable for debugging (in the context of computer science) Code execution depends on the entire software environment. Open-source software is essential, starting with the operating system (e.g., Linux). However, Docker might not be the best tool for encapsulating computing environments (in the context of reproducible research), as it was not initially designed for reproducibility. I suggest exploring Guix, which is purpose-built for reproducible research, and Software Heritage for archiving software.\nYou rightly emphasize the importance of sharing code and data, aligning with the open science movement. It would be helpful to mention tools like Software Heritage and Zenodo for sharing resources. I noticed the mention of a locally managed public repository, KiltHub. If this repository is not accessible to researchers outside Carnegie Mellon University, highlighting alternative platforms like Zenodo remains relevant.\nThe inclusion of Figure 1 might not add value to the reader. This paper is a practical feedback, primarily aimed at showcasing the challenges of reproducing work. Instead, figures illustrating reproducibility workflows or tools (e.g., Table 1) might be more informative.\nWhile Python is widely used due to its ease of use, it is not ideal for reproducibility because of its instability compared to languages like Bash or C, that are more stable. Nonetheless, I agree that results should be reproducible by all, including non-experts, so Python remains a good practical choice.\nThe paper briefly mentions Docker in the introduction but does not elaborate on its usage. It may be more relevant to discuss tools like Guix and Software Heritage, which were explicitly created to address reproducibility challenges. While the paper focuses on Digital Humanities, tools such as CodeOcean (originating from bioinformatics) and FAIR principles are broadly applicable.\nThe paper focus on Python Jupyter notebooks and literate programming is a solid first step for enabling reproducibility. However, other fields like biology and physics, among others, also face reproducibility crises. Broader discussions could include data storage, workflow tools (for example Snakemake to keep it simple), virtual machines, containers, floating-point arithmetic issues, or parallel computing. But of course, the objective of the paper is to present the hackathon, so we cannot talk about everything. I just write it here if you want to take a look.\nComputers, often seen as “black boxes,” create reproducibility challenges across disciplines. A short introduction to computer science and reproducible research should be incorporated into all scientific curricula. I can recommend you the MOOC: https://www.fun-mooc.fr/en/courses/reproducible-research-methodological-principles-transparent-scie/ In addition, I have written one survey about reproducible research, even if it was more oriented to High performance computing, you might benefit from its read: Antunes B, et al., 2024 (Ref 1)\nOne detail: In the PDF version of the paper, the abstract text is not justified. Shouldn’t it be?\nConclusion This hackathon is an excellent initiative to raise awareness among students and young researchers about the challenges of reproducibility. While the paper provides a high-level overview, focusing on literate programming with Jupyter notebooks and the problem of software dependency hell, it serves as a good introduction to the topic.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Not applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Yes",
"responses": []
},
{
"id": "355235",
"date": "07 Jan 2025",
"name": "Teresa Gomez-Diaz",
"expertise": [
"Reviewer Expertise Research Software",
"Research Data",
"Open Science",
"dissemination",
"evaluation"
],
"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\nCASE STUDY A libraries reproducibility hackathon: connecting students to University research and testing the longevity of published code https://f1000research.com/articles/13-1305/v1\nThis case study refers to a hackathon conducted by the members of the Carnegie Mellon University (CMU) Libraries in order to reproduce research results produced by Professor Christopher Warren on data analysis of the Oxford Dictionary of National Biography (ODNB). The event was open for participants coming from CMU and other institutions in the greater Pittsburgh area and was conducted by members of the CMU Libraries. This experience gives an interesting setting to explore reproducibility of published research results by a Professor of the University who also provides data and the produced software involved in the research, and shows a good example of a collaboration between Librarians and members (students?) of the Computer Science School.\nHowever, there are a few points in this manuscript that need attention.\n1. Abstract. As included in the Case Studies guidelines [ https://f1000research.com/for-authors/article-guidelines/case-studies ], abstract should be structured into Background, Methods, Results, and Conclusions . In particular, the conclusions should be better presented in the abstract (and in the manuscript, see later).\n2. Hackathon context. As explained in the document (see also [ https://www.library.cmu.edu/abou)t/news/2024-04/reproducibility-hackathon ], the event was open to a large (institutional) public, but the title of the manuscript refers to students. More insight about the participants (how many, how many students, which level, which scientific background…) should be provided in order to better seize the complexity of the event. Please, clarify if the three authors of the manuscript coming from the Computer Science School where also participants of the event and if they are students or Members of the School. Moreover, it was indicated that “participants could have knowledge and awareness of scientific programming with Python and/or R” was desired, but was not required. Was this a difficulty? How many participants had or had not programming knowledge?\n3. Problems with data and code It is mentioned that: “At this hackathon event, the organizers observed how participants faced challenges with insufficient documentation, data behind a paywall, and problems with code and proprietary software.” But there is no further information about these observations.\n4. Reproducibility success. It is mentioned that: “Of the figures produced in the notebook, fourteen figures were successfully reproduced by Terveen … and eight figures were not successfully reproduced.” Or that “Though there was trial and error, participants were able to successfully reproduce figures from this study”. But which is the percentage of success? How many figures were in the initial work by Prof. Warren and how many were reproduced by all the participants?\n5. Insufficient documentation and code longevity. As noticed by participant Chan, a “requirements.txt” file could help to facilitate the understanding of the software context of the code produced by Prof. Warren. Our work (see Gomez-Diaz T, et al., 2022 [Ref 1]) goes further in this kind of recommendations, proposing flexible procedures for research software and research data dissemination. It is extremely idealistic to expect that software released at some time will find easily runable environments, unless there is the available resources (human, funding) to keep the necessary maintenance of the produced software (who can use Windows version 5?). To accompany the research produced software with good documentation and description of the necessary components will help to get to reproducibility environments, that is, to follow appropriate dissemination procedures will be of help for reproducibility issues. Nevertheless, it will be not always possible to ensure the full reproducibility and, in our opinion, a partial solution consists in to release the research software as free/open source software, where the accessibility and the study of the source code is confirmed by the use of free/open source licenses.\n6. Conclusions. Conclusions are poorly described, and more information on the benefits, found drawbacks and other consequences of the event, for participants, students, Prof. Warren and event organizers should be provided to complete this case study.\n7. References. We would like to suggest the inclusion of these references:\nfor Open Science: UNESCO: UNESCO Recommendation on Open Science. 2021 [Ref 2] for Free/Open Source Software: K. Fogel (2005-2022). Producing Open Source Software. How to Run a Successful Free Software Project, https://producingoss.com for an example of a Journal giving a reproducibility environment for their publications: IPOL Journal · Image Processing On Line [ https://www.ipol.im/ Nicolaï, A., et al., 2022 [Ref 3]\n8. Use of privately owned companies. We would like to raise awareness about the use of privately owned companies like Code Ocean [ https://codeocean.com/ ] for the storage and manipulation of data and code produced within the scientific community. Usually the scientific community is not well aware of legal issues related to the terms of use of these platforms and their consequences, like, for example: `` You hereby grant Code Ocean a worldwide, perpetual, irrevocable, royalty-free right and license to use and exploit any ideas, suggestions, comments, recommendations, enhancement requests or other input provided by you about the Platform to Code Ocean. '' (see point 3. Feedback\nin [ https://codeocean.com/terms-of-use ]). Regarding OSF, the Center for Open Science, Inc. (referred to as \"the COS\", \"Open Science Framework\", \"OSF\") declares to be a nonprofit organization, but also provides with similar terms of use: `` by depositing any Content (including data and links, but not the linked content) in a COS account, you grant the COS a perpetual, irrevocable, worldwide, royalty-free license to store, reproduce, transmit, distribute, publicly perform, and publicly display such Happy… '' (see further information in [ https://github.com/CenterForOpenScience/cos.io/blob/master/TERMS_OF_USE.md ]). Universities and other Research Performing Institutions, and, in particular, University and other institutional Libraries, could study the proposition of University or institutionally owned platforms and/or services to deal with their scientific production.\n9. To complete the background context of this case study, some information on previously hosted hackathons by the CMU Libraries, like Biohackathons and an AI Literacy Resource Hackathon, could be included as they can be of interest for the Hackathon community.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Partly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1305
|
https://f1000research.com/articles/10-1284/v1
|
15 Dec 21
|
{
"type": "Research Article",
"title": "Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice",
"authors": [
"Irene Martín-Estal",
"Oscar R Fajardo-Ramírez",
"Mario Bermúdez De León",
"Carolina Zertuche-Mery",
"Diego Rodríguez-Mendoza",
"Patricio Gómez-Álvarez",
"Marcela Galindo-Rangel",
"Andrea Leal López",
"Inma Castilla-Cortázar",
"Fabiola Castorena-Torres",
"Irene Martín-Estal",
"Oscar R Fajardo-Ramírez",
"Mario Bermúdez De León",
"Carolina Zertuche-Mery",
"Diego Rodríguez-Mendoza",
"Patricio Gómez-Álvarez",
"Marcela Galindo-Rangel",
"Andrea Leal López"
],
"abstract": "Background: During pregnancy, the placenta is an extremely important organ as it secretes its own hormones, e.g. insulin-like growth factor 1 (IGF-1), to ensure proper intrauterine fetal growth and development. Ethanol, an addictive and widely used drug, has numerous adverse effects during pregnancy, including fetal growth restriction (FGR). To date, the molecular mechanisms by which ethanol triggers its toxic effects during pregnancy, particularly in the placenta, are not entirely known. For this reason, a murine model of partial IGF-1 deficiency was used to determine ethanol alterations in placental morphology and AAH expression. Methods: Heterozygous (HZ, Igf1+/-) female mice were given 10% ethanol during 14 days as an acclimation period and throughout pregnancy. HZ female mice given water were used as controls. At gestational day 19, pregnant dams were sacrificed, placentas were collected and genotyped for subsequent studies. Results: IGF-1 deficiency and ethanol consumption during pregnancy altered placental morphology, and decreased placental efficiency and aspartyl/asparaginyl β-hydroxylase (AAH) expression in placentas from all genotypes. No differences were found in Igf1, Igf2, Igf1r and Igf2r mRNA expression in placentas from all groups. Conclusions: IGF-1 deficiency and ethanol consumption throughout gestation altered placental development, suggesting the crucial role of IGF-1 in the establishment of an adequate intrauterine environment that allows fetal growth. However, more studies are needed to study the precise mechanism to stablish the relation between both insults.",
"keywords": [
"placenta",
"IGF-1 deficiency",
"fetal growth restriction",
"ethanol."
],
"content": "Abbreviations\n\nAAH: aspartyl/asparaginyl β-hydroxylase\n\nAKT: protein kinase B\n\ncDNA: complementary DNA\n\nDAB: diaminobenzidine\n\nEDTA: ethylenediaminetetraacetic acid\n\nELISA: enzyme-linked immunosorbent assay\n\neNOS: endothelial nitric oxide synthase\n\nFASD: fetal alcohol spectrum disorders\n\nFGR: fetal growth restriction\n\nHRP: horseradish peroxidase\n\nHZ: heterozygous\n\nIGF-1: insulin-like growth factor 1\n\nIGF-2: insulin-like growth factor 2\n\nIGFBP-1: IGF-1 binding protein 1\n\nIGFBP-3: IGF-1 binding protein 3\n\nIGF1R: IGF-1 receptor\n\nIGF2R: IGF-2 receptor\n\nINSR: insulin receptor\n\nKO: knock-out\n\nMAPK: mitogen-activated protein kinase\n\nPBS: phosphate buffered saline\n\nPCR: polymerase chain reaction\n\nPI3K: phosphoinositide-3-kinase\n\nRT-qPCR: reverse transcription coupled to polymerase chain reaction\n\nSD: standard deviation\n\nWT: wild type\n\n\n1. Introduction\n\nThroughout pregnancy, the placenta is an essential organ for both mother and fetus; being the major determinant of intrauterine growth and serving as a protective barrier against external and internal insults.1\n\nInsulin-like growth factor 1 (IGF-1) is a pleiotropic hormone with several functions: mitochondrial protection,2 cell proliferation and survival,3 tissular growth and development.4 It regulates placental morphogenesis and hormone secretion into umbilical and maternal circulations, processes that are indispensable for fetal development.5 Furthermore, IGF-1, as well as insulin-like growth factor 2 (IGF-2), are key providers of placental resource allocation either for development or for response to external and environmental insults.5–7\n\nTo this day, numerous IGF-1 deficiency conditions have been described in humans, e.g. fetal growth restriction (FGR).8 FGR is a disorder where reduced levels in both IGF-1 and IGF-1 binding protein 3 (IGFBP-3) are observed, suggesting that reduced IGF-1 concentration in the fetus, mother and/or placenta may contribute to growth restriction.8,9 Also, FGR, among other harmful consequences, such as fetal death, miscarriage, low birth weight, premature birth and fetal alcohol spectrum disorders (FASD), can be a result of ethanol consumption during pregnancy .10,11\n\nCurrent experimental studies have shown that chronic exposure to high levels of ethanol during pregnancy reduces fetal weight12 as well as maternal and fetal plasmatic levels of both IGF-1 and IGFBP-3.13 Also, ethanol increases both IGF-1 binding protein 1 (IGFBP-1, an inhibitory protein for IGF-1) and IGF-2 levels,13 inhibits insulin, IGF-1 and IGF-2 placental gene expression and/or secretion12,14 and reduces activities of both insulin and IGF-1 receptors15,16; thus, altering IGF-1 bioavailability and its downstream signaling.\n\nThe molecular mechanism for ethanol toxic effects during pregnancy, specially in the placenta, it is not totally understood. Several studies in animal models of ethanol consumption suggest that this molecule alters the insulin and IGF-1 signaling pathway, impairing cell viability, metabolism, homeostasis, and hence, normal placental growth and development.9,14,17\n\nAspartyl-(asparaginyl) β-hydroxylase (AAH), a type 2 transmembrane protein that hydroxylates epidermal growth factor-like domains of proteins that have a functional role in cell motility and invasion, is regulated by the IGF-1 signaling pathway.18 AAH is overexpressed in trophoblast cells, which are motile and invasive epithelial cells that mediate the appropriate development of placenta and implantation.19 Experimental studies in murine models with chronic ethanol exposure, showed a reduced expression of IGF-1 in placentas, being associated with decreased expression of AAH in trophoblastic cells, suggesting a role of the IGF-1 signaling pathway in placentation and fetal development.9,14\n\nFor this reason, as either IGF-1 deficiency or ethanol consumption during pregnancy produces FGR, the aim of the present study was to determine whether IGF-1 partial deficiency is responsible for placental alterations in morphology and AAH expression, as well as if chronic ethanol exposure during gestation contributed to these placental changes.\n\n\n2. Methods\n\nAs previously reported, IGF-1 heterozygous mice were obtained by cross-breeding transgenic mice, line 129SV and Igf1tm1Ts/ImJ (003258, Jackson Laboratory, Maine, USA) and CD1 (non-consanguineous, Circulo A.D.N S. A de C.V., Ciudad de Mexico, Mexico).20\n\nAnimals were housed in cages in a room with 12-hour light/dark cycle, constant humidity (50–55%) and temperature (20–22°C). Food (PicoLab® Rodent Diet 20 5053*, Missouri, USA) and water were given ad libitum. All experimental procedures were performed in compliance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978), the NORMA Oficial Mexicana (NOM-062-ZOO-1999) for technical specifications to produce, care and use of laboratory animals and the ARRIVE guidelines. Also, all experimental procedures were approved by the Institutional Committee for the Care and Use of Laboratory Animals of Tecnologico de Monterrey (Protocol 2018-006). All efforts were made to ameliorate any suffering of animals, such as minimal handling, adequate space for living and no other experimentation or pain inducing procedures.\n\nThe sample size was calculated using the resource equation method,21 where the value of E is calculated and should lie between 10 and 20 to be considered adequate: E = Total number of animals − Total number of groups = (7 × 2) − 2 = 12.\n\nTwo randomly selected experimental groups of heterozygous (HZ, Igf1+/−) female mice 16±8 weeks old were randomly included in the experimental protocol: one control group given water (HZ–Control, n = 7), and other group given food grade ethanol (HZ–Ethanol, n = 7) (purity: 96%; La Fe, Nuevo Leon, Mexico).\n\nAn adaptation period to ethanol (14 days) was performed, where HZ female mice were given increasing concentrations of 2%, 5% and 10% of ethanol in water, each introduced after a 48-hour acclimation to the previous concentration, according to Kleiber et al.22 During this period, control HZ female mice were provided water (Figure 1).\n\nD: day; GD: gestational day.\n\nAfter the acclimation period to ethanol, HZ male mice were mated overnight with HZ female mice. To avoid ethanol consumption from males during mating, water was given to the ethanol group. Once the vaginal plug was observed, it was considered gestational day one and males were removed. Throughout gestation, 10% ethanol or water was given to pregnant dams (HZ-Ethanol and HZ-Control; respectively), food and beverage consumption and weight gain were monitored throughout the experimental protocol. Nonpregnant females from HZ-Ethanol group were given 10% ethanol during 24 hours and then mated again with male mice. If vaginal plug was not observed after this second mating, ethanol exposed female mice were sacrificed by cervical dislocation. On the other hand, nonpregnant females from HZ-Control group were mated again until the presence of the vaginal plug was observed.\n\nAt gestational day 19 (before the end of the gestational period in mice), pregnant females were sacrificed by cervical dislocation.23,24 Subsequently, blood was collected by cardiac puncture and a caesarean section was performed to obtain fetuses and placentas, which were measured and weighted (Figure 1).\n\nTails from fetuses were cut for genotype determinations. Fetuses and placentas were stored randomly blind in either paraformaldehyde 4%, for histology and immunohistochemistry analyses, or liquid nitrogen, for reverse transcription coupled to polymerase chain reaction (RT-qPCR) determinations.\n\nDNA was extracted from tails of fetuses using the Wizard Genomic DNA Purification Kit (A1125, Promega, Wisconsin, USA) following manufacturer’s instructions, and stored at −20°C until analysis. End-point polymerase chain reaction (PCR) (Veriti 96 well Thermal Cycler, Applied Biosystems, California, USA) was carried out for genotyping using the following set of primers for Igf1 gene: WT forward 5′-TTCATGCCACACTGCTCTTC-3′; common 5′-AGAGGGGATGGGAGAGCTAC-3′; and mutant forward 5′-GCCAGAGGCCACTTGTGTAG-3′. All primers were acquired from IDT (Iowa, USA). Secondly, conventional PCR analysis was achieved using the GoTaq Green Master Mix (M712C, Promega, Wisconsin, USA) following manufacturer’s instructions.\n\nIn order to evaluate serum IGF-1 circulating levels in HZ dams at gestational day 19, sera from control (WT) mice treated both with water (n = 5) or ethanol (n = 5) were also used. Serum IGF-1 levels were determined by enzyme-linked immunosorbent assay (ELISA) using the Mouse/Rat IGF-1 commercial kit (22-IG1MS-E01, Alpco, New Hampshire, USA), following manufacturer’s instructions. The signal was measured using a spectrophotometer Synergy HT (Biotek, Vermont, USA) and data were interpreted using Gen5 Data Analysis Software (Biotek, Vermont, USA).\n\nFor histopathological analysis, placental samples from all experimental groups were fixed in 4% paraformaldehyde diluted in 10 mM phosphate buffered saline (PBS) solution for 24 hours. Once samples were properly fixed, they were dehydrated in increasing ethanol concentrations and were embedded in liquid paraffin using the automated equipment Leica TP 1020 (Leica, Wetzlar, Germany). Sections 4 μm thick were cut using a Reichert Jung Leica BC2030 Histocut Rotary Microtome (Leica, Hesse, Germany) and subsequently stained with hematoxylin-eosin (HHS32 and 2853, Sigma-Aldrich, Missouri, USA). Finally, all histological preparations were evaluated independently by three observers (double-blind) in a Zeiss Axio Imager M2 microscope (Zeiss, Baden-Württemberg, Germany) to establish morphology alterations in the placenta due to ethanol consumption throughout gestation.\n\nAll images were analysed using the processing package ImageJ (National Institutes of Health, Maryland, USA) (RRID:SCR_003070). The area of the junctional zone of the placenta was evaluated according to the presence of trophoblasts in this placental zone. Three images were taken per sample of at least three individuals from each group and genotype.\n\nParaffin-embedded placental tissues were deparaffinized and rehydrated in decreasing ethanol concentrations. Sample sections were incubated with 3% hydrogen peroxide at room temperature in darkness for 30 minutes to inactivate endogenous peroxidases. Retrieval of antigen was induced with 2 mM ethylenediaminetetraacetic acid (EDTA) pH 8.0 and 50 mM Tris–HCl pH 9.0 by microwave heating at 100°C for 8 minutes. Sections were incubated overnight at 4°C with specific primary antibodies: rabbit anti-ASPH (362200, USBiological Life Sciences, Massachusetts, USA) diluted at 1:200; or rabbit anti-β actin (ab8227, Abcam, Cambridgeshire, United Kingdom) diluted at 1:1,000, the latter being an endogenous control. Afterwards, primary antibodies sections were incubated with goat anti-rabbit IgG H&L (horseradish peroxidase, HRP) (ab205718, Abcam, Cambridgeshire, United Kingdom) diluted at 1:5,000 for one hour at room temperature. Staining was developed using Steady Diaminobenzidine (DAB)/Plus kit (ab103723, Abcam, Cambridgeshire, United Kingdom) following manufacturer’s instructions. Negative controls were conducted by omitting the primary antibody.\n\nDigital images of tissue sections (five images per placenta) were captured by three observers (double-blind) using a Zeiss Axio Imager M2 microscope. All images were analysed using the processing package ImageJ (National Institutes of Health, Maryland, USA).\n\nRNA was isolated from placentas using Trizol reagent (15596026, Invitrogen, California, USA). Quality was checked by the A260/A280 ratio using the Nanodrop 2000 Spectrophotometer (Thermo Scientific, Massachusetts, USA), whereas integrity was determined by electrophoresis in 1% agarose gel. Samples were stored at −80°C until analysis. Subsequently, the SuperScript III First-Strand Synthesis System (Invitrogen, California, USA) was utilized to prepare complementary DNA (cDNA) from 500 ng of the total RNA, according to the manufacturer’s instructions.\n\nFor the PCR analyses, TaqMan Universal PCR Master Mix (Thermofisher, Massachusetts, USA) was used in a total volume of 20 μL containing 400 nM of each oligonucleotide and 200 mM of specific Taqman® probes for particular genes, supplied by Applied Biosystems (California, USA) (Supplementary table 1). The assays were performed in a 96-well reaction plate on a Quant Studio 3.0 thermocycler (Applied Biosystems, California, USA). Ribosomal 18S RNA expression was used as an endogenous control (Applied Biosystems, California, USA).\n\nEach sample was run in triplicate, and negative controls were included in the same plate. Results were analyzed using the comparative threshold cycle method for relative gene expression.25\n\nAll data are represented by mean±standard deviation (SD). Significance was estimated with non parametric (Mann–Whitney U test and Kruskal–Wallis test) or parametric (Student T test and ANOVA) statistical tests, using Mann–Whitney U test or Student T test to compare between two groups (for example between HZ-Control and HZ-Ethanol groups), whereas comparisons among more than two groups were carried out using the Kruskal-Wallis test or ANOVA (for example, comparisons between WT, HZ and knock-out (KO) placentas). To evaluate the effect of the two independent variables in the present study (ethanol consumption and IGF-1 deficiency) a general linear model was performed. Differences were considered significant at a level of p < 0.05. Statistical analyses were performed on SPSS 26 (IBM, New York, USA) (RRID:SCR_019096) and graphs were generated on Prism 8.2.1 (GraphPad Software, California, USA) (RRID:SCR_002798).\n\n\n3. Results\n\nIn order to validate IGF-1 serum levels in the present experimental model, control (WT) pregnant female mice treated with water or ethanol were used. At gestational day 19, as expected, IGF-1 serum levels in HZ pregnant dams (HZ-Control, 454 ± 58 ng/mL, and HZ-Ethanol, 422 ± 43 ng/mL) were decreased compared to WT female mice (WT-Control, 739 ± 48 ng/mL, and WT-Ethanol, 795 ± 147 ng/mL) (p < 0.001). HZ-Control and HZ-Ethanol dams had significant lower IGF-1 serum levels than WT-Control female mice (p < 0.05 and p < 0.01, respectively). Interestingly, a possible synergic effect, that decreased IGF-1 serum levels, was observed by the partial IGF-1 deficiency and ethanol consumption (HZ-Ethanol) during gestation compared to WT-Control group (p < 0.01).\n\nThe placenta is conformed of several strata, such as myometrium, decidua, junctional zone and labyrinth (Extended data: figure 1). In the WT placentas from the control group all morphology and structure that characterizes these layers were well defined (Figure 2A). It was observed that IGF-1 deficiency promoted a disorganization in placental strata, specially in the junctional zone, where trophoblast cells were observed (Figure 2B). Remarkably, an abnormal placental development was observed in KO placentas from the control group, where trophoblasts were arrested in islets (Figure 2C). Ethanol consumption throughout gestation exacerbated placental layer disorganization and promoted throphoblast arrest in islets in all groups (WT, HZ and KO) (Figures 2D, 2E and 2F). Additionally, ethanol use altered trophoblast migration (Figure 2D) and promoted placental hypoplasia, particularly in HZ and KO placentas (Figures 2E and 2F). Due to the variability between all experimental groups, no significant differences were observed in the area of the junctional zone of the placenta (data not shown); in this area a clear disorganization is detected with both IGF-1 deficiency and ethanol consumption.\n\nPlacentas from WT, HZ and KO fetuses from pregnant dams given water (A, n = 5; B, n = 6; and C, n = 6) or ethanol (D, n = 7; E, n = 6; and F, n = 5) were stained with hematoxylin & eosin and examined by light microscopy. Representative images from one placenta of fetuses from each group are included. Black arrows indicate trophoblast islets, suggesting an abnormal migration. IGF-1 deficiency promoted placental disorganization, especially in the junctional zone; ethanol consumption during gestation exacerbated such disorganization. Original magnification 100×. Scale bar = 100 μm.\n\nPlacental efficiency is frequently defined as the grams of fetus produced per gram of placenta, being an indicator of the ability of this organ to maintain an adequate nutrient supply to the fetus.26–28 The chronic exposure to ethanol during gestation resulted in a significant reduction in placental efficiency (p < 0.001) compared to control groups. Subsequently, genotype offspring outcome was evaluated, showing that IGF-1 deficiency significantly decreased placental efficiency in KO placentas compared to WT placentas (p < 0.05) and HZ placentas (p < 0.01) from control group (Figure 3). Also, ethanol consumption during gestation significantly reduced placental efficiency in KO placentas compared to WT and HZ placentas from ethanol treated group (p < 0.001 in both cases) (Figure 3). Markedly, there was a significant diminution in 0.75-fold in placental efficiency in KO ethanol treated placentas compared to KO placentas from control group (p < 0.05) (Figure 3).\n\nData are represented as mean ± standard deviation. The statistical tests used were Student T test to compare between two groups, and general linear model to evaluate the effect of the two independent variables in the present study (ethanol consumption and IGF-1 deficiency). Differences were considered significant at a level of p < 0.05.\n\nTo determine ethanol’s harmful effects on placental development, protein expression levels of AAH were determined by immunohistochemistry. AAH was predominantly expressed in the junctional zone, as shown in WT placentas from control group (Figure 4A). IGF-1 deficiency revealed a decrease in AAH expression within the junctional zone in both HZ and KO placentas compared with WT placentas from control group (Figures 4B and 4C). Ethanol consumption during gestation also decreased AAH expression, especially in HZ and KO placentas, denoting the aforementioned alterations in placental morphology, particularly in the junctional zone, where trophoblasts are arrested in islets, avoiding their correct migration towards the junctional zone for an appropriate placental development (Figures 4D, 4E and 4F).\n\nOriginal magnification 100x. Representative images from one mice of each group are included. Red arrows denote AAH expression in the junctional zone of the placenta, where trophoblast cells are expressed. Blue arrows indicate trophoblast islets. G) Effect of ethanol consumption during gestation in Asph gene expression in placentas from WT, HZ and KO fetuses from pregnant dams given water or ethanol (n = 4 per group). The statistical tests used were Mann-Whitney U to compare between two groups, ANOVA or Kruskal-Wallis test to compare between more than two groups, and general linear model to evaluate the effect of the two independent variables in the present study (ethanol consumption and IGF-1 deficiency). Differences were considered significant at a level of p < 0.05.\n\nThe placental expression of components from the IGF-1 signaling pathway (Insulin-like growth factor 1 (Igf1), Insulin-like growth factor 2 (Igf2), Insulin-like growth factor 1 receptor (Igf1r), Insulin-like growth factor 2 receptor (Igf2r) and Aspartyl/asparaginyl β-hydroxylase (Asph)) was analyzed by RT-qPCR. No significant differences were found in Igf1 and Igf2 expression level between both treatments (control and ethanol). When grouped by genotype, no significant differences were found (Table 1).\n\nRegarding Igf1r and Igf2r expression, a significant increase in Igf1r was observed with ethanol consumption throughout gestation (p < 0.05). When grouped by genotype, no significant differences were observed (Table 1).\n\nWhen Asph expression levels were evaluated, no significant differences were shown between both treatments (water or control, and ethanol). When grouped by genotype, a significant increase in Asph expression was observed in KO placentas compared to WT (p < 0.05) and HZ (p < 0.05) placentas from control group, whereas ethanol treatment seemed to have an increase effect in WT and HZ placentas (Figure 4G).\n\n\n4. Discussion\n\nThe placenta is an exciting organ, as it performs crucial roles during intrauterine development: nutrient and oxygen supply to the fetus, exchange of waste products between mother and fetus, metabolism of various molecules, and hormone production and secretion. Also, this organ can operate as a barrier to avoid infections, maternal diseases and propagation of xenobiotics, contributing to a suitable fetal development.29 However, the placenta continues to be an mysterious organ, as there are still many questions to be solved.\n\nGestation is an intricate process where, additionally to the reorganization of the mother’s organs, numerous adaptations in the endocrinological axis occur to prepare fetal development. For example, IGF-1 serum levels increase during pregnancy, especially in the first trimester, and continue to rise throughout this period30 in order to provide a suitable intrauterine environment for fetal and placental growth.31 Results in this project showed that ethanol consumption during gestation significantly affects IGF-1 serum levels in HZ pregnant dams, according to existing literature.32\n\nThe placenta is composed of by several strata, such as myometrium, decidua, junctional zone (cytotrophoblast and syncytiotrophoblast layers) and labyrinth, each presenting certain characteristics that allow the placenta to achieve its functions properly.33 The major source of placental hormones is the syncytiotrophoblast layer, e.g., IGF-1 is produced and secreted in this stratum.34,35 Recently, reduced IGF-1 levels have been associated with several pathologies, such as FGR,8,36,37 a consequence of ethanol consumption.38 Results herein revealed that both IGF-1 deficiency and ethanol consumption during gestation promoted placental disorganization, particularly in the junctional zone, where trophoblasts are arrested in islets, highlighting the crucial role of IGF-1 in placental development.\n\nAccording to these results, ethanol consumption during gestation in the present experimental model aggravated placental disorganization and promoted placental hypoplasia, particularly in IGF-1 deficient placentas, suggesting a synergic effect between both issues, that could lead to poor placental development and, hence, an abnormal fetal growth. One of the main determinants of placental formation and function are trophoblasts, located in junctional and labyrinth zones of the placenta, the major cell type affected by ethanol consumption. Ethanol consumption during gestation can lead to an altered trophoblast motility and invasion, resulting in a distorted placental barrier thickness and abnormal development that can promote an aberrant nutrient exchange, producing impairments in fetal growth and development.39,40\n\nSeveral studies conducted in mice, pigs and sheeps have disclosed that IGF-1 exogenous treatment during gestation improves nutrient transport and waste exchange between mother and fetus, enhancing fetal growth and development.26 In this context, lower placental efficiency results in reduced birth weight, which translates as an inefficient placenta that failed to adapt its nutrient supply to meet the demands of the rapidly growing fetus.27,28 Results herein showed that IGF-1 deficiency decreased placental efficiency especially in KO placentas, being these fetuses the smallest ones, highlighting the crucial role of this hormone in placental development.41\n\nResults herein reported showed that ethanol decreased placental efficiency specially in KO placentas, suggesting a key role of IGF-1 in placental formation and function necessary for a suitable fetal development. In this sense, ethanol consumption during gestation also reduces placental efficiency due to reductions in angiogenesis-related proteins.42,43 However, the results suggest that ethanol consumption during gestation did not gravely affect the development of HZ embryo-placenta units. This could be due to the intricate genetics of the placenta, being noted that it is an organ conformed of a fetal part and a maternal part, which are in constant communication. Both parts are necessary for the appropriate development of this organ, being able to be affected in the same way by external factors, such as IGF-1 deficiency and/or ethanol consumption.\n\nIn vivo experimental studies of ethanol consumption during gestation have revealed that ethanol use diminishes AAH expression (both mRNA and protein levels) and, hence, trophoblast survival, motility and invasion; resulting in distorted vascular remodeling and placentation.14,44,45 In vitro studies with human trophoblastic cells have revealed that small interfering RNA inhibition of AAH reduced Notch signaling, impairing trophoblastic cell motility, both effects related to altered fetal growth.46 Our results showed a decrease in AAH protein expression due to IGF-1 deficiency, mainly in the junctional zone, where trophoblast cells are located. Ethanol consumption throughout gestation promoted the arrest of trophoblasts in islets and also reduced AAH expression in the junctional zone of HZ and KO placentas, thus altering placental morphology. Regarding to mRNA expression levels, IGF-1 deficiency showed a significant increase in Asph expression in KO placentas from control group, while ethanol consumption during gestation also exhibited an increase in Asph in WT and HZ placentas, suggesting that a mechanism is taking place in order to promote IGF-1 downstream signaling expression to try to stimulate placental development despite IGF-1 deficiency and ethanol consumption. Also of note, although there is no information on other proteins that regulate AAH in the placenta, there are other protein entities that modulate its expression and would be interesting to evaluate.47\n\nIGF-1 plays a crucial role in placental and fetal development through binding to its putative receptor (IGF1R). Also, IGF-1 can bind to IGF-2 receptor (IGF2R) or to insulin receptor (INSR), but with lower affinity. The majority of these receptors are members of the tyrosine kinase family, activating two main downstream signaling pathways: the mitogen-activated protein kinase (MAPK) and the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) cascades, both related to cell survival, growth and proliferation, e.g. trophoblast cell migration to establish the maternal–fetal interface that allows nutrient exchange between mother and fetus across the placenta.35 Several studies conducted in human FGR placentas have shown an increase in Igf2 and Igf1r expression levels and activated INSR, and a reduction in IGF1R protein content, with no change in Igf1, Insr and Igf2r expression levels, suggesting a placental compensatory mechanism in response to growth retardation.48,49 In contrast, experimental studies in rats have shown reduced Igf1r expression in FGR placentas, with no change in Insr expression, suggesting a decreased nutrient delivery across the placenta that would reduce the growth-promoting effects of insulin-like growth factors.50 In this way results herein disclosed that no significant differences were observed in Igf1, Igf2, Igf1r and Igf2r placental expression levels due to IGF-1 deficiency. These differing results suggest that more studies are needed to elucidate the role of IGF-1 downstream molecules in intrauterine growth.\n\nThe present study had some limitations. RT-qPCR analyses have revealed that the regulation of the IGF-1 signaling pathway in the placenta is very complex, especially when there are two independent variables (IGF-1 deficiency and ethanol consumption) to analyze. More studies are needed to investigate the regulation of this cascade at protein level, such as the phosphorylation level of the molecular components of the IGF-1 signaling pathway or caspase levels to observe apoptosis. Additionaly, mouse placentas have a small size, so it would be more convenient to use rat placentas, which are even more similar to human placentas, allowing a better separation and analysis of placental layers. The present study showed that IGF-1 deficiency and ethanol consumption during pregnancy impaired AAH expression in the placenta. However, more studies are needed to determine the crucial role of this enzyme in trophoblastic cell migration to promote placentation. These future experiments would allow detailed study the placenta as a valuable organ to serve as a diagnostic tool to identify novel biomarkers for detecting the outcome of IGF-1 deficiency and/or ethanol’s teratogenicity.\n\n\n5. Conclusions\n\nTo conclude, the present study discloses that both IGF-1 deficiency and ethanol consumption during pregnancy promote placental disorganization, particularly in the junctional zone where trophoblast cells are expressed, and decrease placental efficiency, thus altering placental development and fetal growth. In addition, both parameters alter AAH protein expression in the placenta, suggesting an abnormal placental development.\n\n\nData availability\n\nZenodo: Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice. https://doi.org/10.5281/zenodo.575015551\n\nThis project contains the following underlying data:\n\n- Figure 2A_H&E Image Placenta WT (Control) 10×.tif\n\n- Figure 2B_H&E Image Placenta HZ (Control) 10×.tif\n\n- Figure 2C_H&E Image Placenta KO (Control) 10×.tif\n\n- Figure 2D_H&E Image Placenta WT (Ethanol) 10×.tif\n\n- Figure 2E_H&E Image Placenta HZ (Ethanol) 10×.tif\n\n- Figure 2F_H&E Image Placenta KO (Ethanol) 10×.tif\n\n- Figure 4A_AAH 1/200 Image Placenta WT (Control) 10×.tif\n\n- Figure 4B_AAH 1/200 Image Placenta HZ (Control) 10×.tif\n\n- Figure 4C_AAH 1/200 Image Placenta KO (Control) 10×.tif\n\n- Figure 4D_AAH 1/200 Image Placenta WT (Ethanol) 10×.tif\n\n- Figure 4E_AAH 1/200 Image Placenta HZ (Ethanol) 10×.tif\n\n- Figure 4F_AAH 1/200 Image Placenta KO (Ethanol) 10×.tif\n\n- Figure 3_Placental efficiency Raw data.xlsx\n\n- Table 1 and Figure 4G_RT-PCR Raw data.xlsx\n\n- Raw data for RT-qPCR analysis.xls\n\nZenodo: Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice. https://doi.org/10.5281/zenodo.575015551\n\nThis project contains the following extended data:\n\n- Extended data Figure 1_H&E Image Placenta 1.25×.tif\n\nZenodo: Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice. https://doi.org/10.5281/zenodo.575015551\n\n- ARRIVE checklist.pdf (The ARRIVE guidelines 2.0)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAuthor’s contributions\n\nM-EI conceived, designed, developed and performed the experiments, manuscript writing, generated the first draft and successive versions of the manuscript; F-ROR designed the experiments and data analysis; BLM resource acquisition, discussion and manuscript edition; Z-MC, G-R M and LLA developed the experiments; RMD histological analysis; G-AP reviewed bibliography; C-CI conceived and designed the study and experimental model, data analysis and manuscript writing; C-TF conceived and designed the experiments, data analysis, contributed with reagents/materials/analysis tools, generated the first draft and successive versions of the manuscript. All authors revised and approved manuscript’s final version.",
"appendix": "Acknowledgements\n\nThe authors would like to express their gratitude to QBP. María Isabel García Cruz. Also, M-EI wants to show gratitude to the Tecnologico de Monterrey for the scholarship awarded for the completion of the Ph.D.\n\n\nReferences\n\nGude NM, Roberts CT, Kalionis B, et al.: Growth and function of the normal human placenta. Thromb. Res. 2004; 114: 397–407. PubMed Abstract | Publisher Full Text\n\nPérez R, García-Fernández M, Díaz-Sánchez M, et al.: Mitochondrial protection by low doses of insulin-like growth factor-I in experimental cirrhosis. World J. Gastroenterol. 2008; 14: 2731–2739. PubMed Abstract | Publisher Full Text\n\nVincent AM, Feldman EL: Control of cell survival by IGF signaling pathways. Growth Horm. IGF Res. 2002; 12: 193–197. Publisher Full Text\n\nFowden AL, Forhead AJ: Endocrine interactions in the control of fetal growth. Nestle Nutr. Inst. Workshop Ser. 2013; 74: 91–102. 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PubMed Abstract | Publisher Full Text\n\nHayward CE, Lean S, Sibley CP, et al.: Placental Adaptation: What Can We Learn from Birthweight:Placental Weight Ratio?. Front. Physiol. 2016; 7. PubMed Abstract | Publisher Full Text\n\nMartín-Estal I, Rodriguez-Zambrano MA, Castilla-Cortázar I: Biochemical Assessment of Placental Function. Fetal Growth Restrict. 2019; 83–116. Cham: Springer International Publishing. Publisher Full Text\n\nYang Y, Calakos N: Presynaptic long-term plasticity. Front. Synaptic Neurosci. 2013; 5. PubMed Abstract | Publisher Full Text\n\nAnderlová K, Cinkajzlová A, Šimják P, et al.: Insulin-Like Growth Factor Axis in Pregnancy and Gestational Diabetes Mellitus. Physiol. Res. 2019; 68: 807–816. PubMed Abstract | Publisher Full Text Reference Source\n\nDal Maso L, La Vecchia C, Augustin LSA, et al.: Relationship between a wide range of alcohol consumptions, components of the insulin-like growth factor system and adiponectin. Eur. J. Clin. Nutr. 2007; 61: 221–225. PubMed Abstract | Publisher Full Text\n\nFurukawa S, Tsuji N, Sugiyama A: Morphology and physiology of rat placenta for toxicological evaluation. J. Toxicol. Pathol. 2019; 32: 1–17. PubMed Abstract | Publisher Full Text\n\nCosta MA: The endocrine function of human placenta: an overview. RBM Online. 2016; 32: 14–43. PubMed Abstract | Publisher Full Text\n\nMartín-Estal I, Castilla-Cortázar I, Castorena-Torres F: The Placenta as a Target for Alcohol During Pregnancy: The Close Relation with IGFs Signaling Pathway. Rev. Physiol. Biochem. Pharmacol. 2021. PubMed Abstract | Publisher Full Text\n\nKoutsaki M, Sifakis S, Zaravinos A, et al.: Decreased placental expression of hPGH, IGF-I and IGFBP-1 in pregnancies complicated by fetal growth restriction. Growth Horm. IGF Res. 2011; 21: 31–36. PubMed Abstract | Publisher Full Text Reference Source\n\nLee MH, Jeon YJ, Lee SM, et al.: Placental gene expression is related to glucose metabolism and fetal cord blood levels of insulin and insulin-like growth factors in intrauterine growth restriction. Early Hum. Dev. 2010; 86: 45–50. PubMed Abstract | Publisher Full Text Reference Source\n\nAros S, Mills JL, Iñiguez G, et al.: Effects of prenatal ethanol exposure on postnatal growth and the insulin-like growth factor axis. Horm. Res. Paediatr. 2011; 75: 166–173. PubMed Abstract | Publisher Full Text\n\nColl TA, Chaufan G, Pérez-Tito LG, et al.: Cellular and molecular oxidative stress-related effects in uterine myometrial and trophoblast-decidual tissues after perigestational alcohol intake up to early mouse organogenesis. Mol. Cell. Biochem. 2018; 440: 89–104. PubMed Abstract | Publisher Full Text\n\nKalisch-Smith JI, Outhwaite JE, Simmons DG, et al.: Alcohol exposure impairs trophoblast survival and alters subtype-specific gene expression in vitro. Placenta. 2016; 46: 87–91. PubMed Abstract | Publisher Full Text Reference Source\n\nCrossey PA, Pillai CC, Miell JP: Altered placental development and intrauterine growth restriction in IGF binding protein-1 transgenic mice. J. Clin. Invest. 2002; 110: 411–418. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKwan STC, Presswood BH, Helfrich KK, et al.: An interaction between fetal sex and placental weight and efficiency predicts intrauterine growth in response to maternal protein insufficiency and gestational exposure window in a mouse model of FASD. Biol. Sex Differ. 2020; 11: 40. PubMed Abstract | Publisher Full Text\n\nSavage DD, Rosenberg MJ, Coquet L, et al.: Ethanol-Induced Alterations in Placental and Fetal Cerebrocortical Annexin-A4 and Cerebral Cavernous Malformation Protein 3 Are Associated With Reductions in Fetal Cortical VEGF Receptor Binding and Microvascular Density. Front. Neurosci. 2020; 14. PubMed Abstract | Publisher Full Text\n\nHolbrook BD, Davies S, Cano S, et al.: The association between prenatal alcohol exposure and protein expression in human placenta. Birth defects Res. 2019; 111: 749–759. PubMed Abstract | Publisher Full Text\n\nLui S, Jones RL, Robinson NJ, et al.: Detrimental effects of ethanol and its metabolite acetaldehyde, on first trimester human placental cell turnover and function. PLoS One. 2014; 9: e87328. PubMed Abstract | Publisher Full Text\n\nGundogan F, Bedoya A, Gilligan J, et al.: siRNA inhibition of aspartyl-asparaginyl β-hydroxylase expression impairs cell motility, Notch signaling, and fetal growth. Pathol. Res. Pract. 2011; 207: 545–553. PubMed Abstract | Publisher Full Text\n\nZheng W, Wang X, Hu J, et al.: Diverse molecular functions of aspartate β-hydroxylase in cancer (Review). Oncol. Rep. 2020; 44: 2364–2372. PubMed Abstract | Publisher Full Text\n\nAbu-Amero SN, Ali Z, Bennett P, et al.: Expression of the insulin-like growth factors and their receptors in term placentas: A comparison between normal and IUGR births. Mol. Reprod. Dev. 1998; 49: 229–235. PubMed Abstract | Publisher Full Text\n\nLaviola L, Perrini S, Belsanti G, et al.: Intrauterine Growth Restriction in Humans Is Associated with Abnormalities in Placental Insulin-Like Growth Factor Signaling. Endocrinology. 2005; 146: 1498–1505. PubMed Abstract | Publisher Full Text\n\nReid GJ, Flozak AS, Simmons RA: Placental expression of insulin-like growth factor receptor-1 and insulin receptor in the growth-restricted fetal rat. J. Soc. Gynecol. Investig. 2002; 9: 210–214. PubMed Abstract | Publisher Full Text\n\nMartín-Estal I, Fajardo-Ramirez OR, Bermúdez de León M, et al.: Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient mice.2021. Publisher Full Text"
}
|
[
{
"id": "199303",
"date": "03 Oct 2023",
"name": "Ludivine Doridot",
"expertise": [
"Reviewer Expertise Reproductive biology"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nGeneral comment:\nMartín-Estal et al. performed a well-planned study to evaluate the effect of ethanol consumption on placental development (and fetal growth) in mice partially deficient for IGF1, as well as a potential synergy between (partial or total) IGF-1 deficiency and ethanol consumption on placental development. They notably showed that total IGF-1 deficiency and ethanol consumption both led to structural anomalies in the placental layers. They also showed a reduced placental efficiency in IGF-1 KO placentas, that was further reduced by ethanol consumption. They also evaluated the mRNA and protein expression of AAH and the mRNA expression of a few other genes.\nWhile the data are interesting, their description and analysis is not sufficient. The fetal weight is an important element and thus should be presented. Fetal growth retardation/restriction is indeed a key aspect of IGF-1 signaling and ethanol consumption, as it is well described in the introduction. I would suggest adding 2 panels to Figure 3 with the fetal and placental weight (in addition to the ratio), this is especially important as the authors mentioned placental hypoplasia that is not visible in the presented data. The placental morphology should be analyzed more thoroughly with for example a quantification of the length ratio between JZ/labyrinth and/or the number of abnormal islets in the labyrinth (the quality of the image should also be improved as the text within the image is hardly readable). The AAH immunohistochemistry would also benefit for a quantification analysis (in specific layers). For all the quantitative data, the statistical analysis effectively used should be described with the indication of the number of analyzed samples per group. Post hoc test should be performed after two-way ANOVA or Kruskal Wallis test, to compare the genotypes within the water or ethanol group, and compare the effect of ethanol within each genotype. Only with these additional analyses will it be possible to conclude more clearly on the results.\nMore specific comments:\nIn Figure 3, there are Control: WT, n = 9; HZ, n = 32; KO, n = 22; Ethanol: WT, n = 23; HZ, n = 44; KO, n = 16. This does not fit with the expected ratio of 25/50/25% of WT/HZ/KO. It seems that there are some missing control WT. Could the authors explain this? And for the RT-qPCR, it does not seem that all these placentas were analyzed. How were the one included chosen?\nSyncytiotrophoblast are in the labyrinth layer and not the junctional zone (see for example 10.3389/fimmu.2021.771054). The myometrium is not part of the placenta.\nFor clarity, I would suggest to use Igf+/+, Igf +/- and Igf-/- rather than WT, HZ and KO throughout the manuscript.\nThe author should also discuss the fact that the decidua is always partially deficient in IGF1 which may influence placental establishment, as well as the disparity of mice age that could also influence the results.\nDid the ethanol consumption influence the weight gain of the mice throughout the study?\nHow many HZ-ethanol female were actually mated?\nThe title should be : Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient placentas\nIs the fetal weight further reduced in Ethanol KO compared to water-KO?\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": "11203",
"date": "09 Dec 2024",
"name": "Fabiola Castorena Torres",
"role": "Author Response",
"response": "Monterrey, March 4th 2024 Dear Editorial Board members, First of all, I would like to thank you for your kind answer as for carefully revising the manuscript, that has greatly aimed us to improve our manuscript. Herein we will outline any changes made to the manuscript following reviewers’ advice (changes are shown in green in the manuscript) or, to the contrary, giving a rationale when a suggestion was not implemented. Reviewer 1: Martín-Estal et al. performed a well-planned study to evaluate the effect of ethanol consumption on placental development (and fetal growth) in mice partially deficient for IGF1, as well as a potential synergy between (partial or total) IGF-1 deficiency and ethanol consumption on placental development. They notably showed that total IGF-1 deficiency and ethanol consumption both led to structural anomalies in the placental layers. They also showed a reduced placental efficiency in IGF-1 KO placentas, that was further reduced by ethanol consumption. They also evaluated the mRNA and protein expression of AAH and the mRNA expression of a few other genes. We would like to thank the reviewer for his/her comments, which have helped us to improve the manuscript. While the data are interesting, their description and analysis is not sufficient. The fetal weight is an important element and thus should be presented. Fetal growth retardation/restriction is indeed a key aspect of IGF-1 signaling and ethanol consumption, as it is well described in the introduction. The reviewer is right. This information about fetal parameters (fetal weight, fetal height and placental weight) is presented in the following article of our research group: “Martín-Estal, I., et al. (2022). Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System. Biology, 11(9), 1264. https://doi.org/10.3390/biology11091264”. I would suggest adding 2 panels to Figure 3 with the fetal and placental weight (in addition to the ratio), this is especially important as the authors mentioned placental hypoplasia that is not visible in the presented data. The reviewer is right. Information is presented in the following article of our research group: “Martín-Estal, I., et al. (2022). Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System. Biology, 11(9), 1264. https://doi.org/10.3390/biology11091264”. The placental morphology should be analyzed more thoroughly with for example a quantification of the length ratio between JZ/labyrinth and/or the number of abnormal islets in the labyrinth (the quality of the image should also be improved as the text within the image is hardly readable). Thanks for the reviewer’s comments. Nevertheless, the quantification of the length ratio between JZ/labyrinth was performed, but no significant results were obtained (data not shown). The layout of images in Figure 2 was changed to make it more readable. The AAH immunohistochemistry would also benefit for a quantification analysis (in specific layers). For all the quantitative data, the statistical analysis effectively used should be described with the indication of the number of analyzed samples per group. The reviewer is right. However, a quantification analysis of the immunohistochemistry images was accomplished, but no significant results were obtained (data not shown). Post hoc test should be performed after two-way ANOVA or Kruskal Wallis test, to compare the genotypes within the water or ethanol group, and compare the effect of ethanol within each genotype. Only with these additional analyses will it be possible to conclude more clearly on the results. After two-way ANOVA, two post-hoc tests were executed with SPSS software: Bonferroni and Tukey tests. More specific comments: In Figure 3, there are Control: WT, n = 9; HZ, n = 32; KO, n = 22; Ethanol: WT, n = 23; HZ, n = 44; KO, n = 16. This does not fit with the expected ratio of 25/50/25% of WT/HZ/KO. It seems that there are some missing control WT. Could the authors explain this? Because of the treatment scheme being used in the present study, a greater number of females in the HZ-Ethanol group was used to decrease the risk of death or early delivery due to ethanol treatment. And for the RT-qPCR, it does not seem that all these placentas were analyzed. How were the one included chosen? To reduce variability between groups, only male fetuses were selected for RT-PCR analysis. In addition, the animal model could not be continued due Biotherium issues. Syncytiotrophoblast are in the labyrinth layer and not the junctional zone (see for example 10.3389/fimmu.2021.771054). The myometrium is not part of the placenta. Thanks for your comments. Trophoblast giant cells, the invasive cells responsible for invading maternal vasculature to promote placental development, are located in the labyrinth. However, spongiotrophoblast cells and glycogen trophoblast cells are found in the labyrinth and in the junctional zone (10.3390/nu15163564). Throphoblast invasion is observed in the junctional zone, in order to develop a normal placenta. Alterations in this trophoblast migration can lead to adverse pregnancy consequences due to a limit blood flow, such as fetal growth restriction and preeclampsia (10.1067/mob.2002.127305). For clarity, I would suggest to use Igf+/+, Igf +/- and Igf-/- rather than WT, HZ and KO throughout the manuscript. Thanks for the reviewer’s suggesting. The “Animals and experimental design” section explains the nomenclature used: WT (Igf1+/+); HZ (Igf1+/-) and KO (Igf1-/-). We select that nomenclature because it was used in previous studies carried out by the research group with the present experimental model. The author should also discuss the fact that the decidua is always partially deficient in IGF1 which may influence placental establishment, as well as the disparity of mice age that could also influence the results. Although the decidua, which is in contact with the maternal side, is always partially deficient in IGF-1, the rest of the placenta depends on the fetus; that is, if the fetus is WT, the placenta will be of the same genotype. Also, IGF-2 has an important role in fetal growth due to its direct anabolic actions within the fetus, and by its modulation of placental supply capacity, which may be a compensatory mechanism for IGF-1 deficiency (10.1016/j.placenta.2018.01.005) (Lines: 385-388). On the other hand, the difference in age is not a large period, since it is a difference of 8 weeks, which is equivalent to 6.6 years in humans, a period in which the mice are still reproductively young (10.1016/j.lfs.2015.10.025). Did the ethanol consumption influence the weight gain of the mice throughout the study? Maternal parameters such as weight gain of pregnant dams, average of food and beverage consumption where measured throughout gestation. It was found that both HZ groups (HZ-Control and HZ-Ethanol) weighed less than the WT groups (WT-Control and WT-Ethanol), and this parameters was not affected by ethanol treatment. These results were reported in the following article: “Martín-Estal, I., et al.(2022). Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System. Biology, 11(9), 1264. https://doi.org/10.3390/biology11091264”. How many HZ-ethanol female were actually mated? In HZ-Ethanol group, 9 female mice were mated with HZ male mice. The title should be: Ethanol consumption during gestation promotes placental alterations in IGF-1 deficient placentas. The reviewer is right. We will change the title as suggested, thanks. Is the fetal weight further reduced in Ethanol KO compared to water-KO? This result was reported in the following article: “Martín-Estal, I., et al. (2022). Effect of Ethanol Consumption on the Placenta and Liver of Partially IGF-1-Deficient Mice: The Role of Metabolism via CYP2E1 and the Antioxidant Enzyme System. Biology, 11(9), 1264. https://doi.org/10.3390/biology11091264”. In this article, the presence of KO genotype and ethanol consumption affected fetal height and weight when compared to the WT and HZ genotypes. Yours faithfully, Inma Castilla de Cortázar Larrea, MD, PhD. Professor of Medical Physiology HM Velazquez Cabinet Velazquez 25, 28001 Madrid, Spain Fabiola Castorena Torres, PhD. Research Professor, Coordinator of the Postgraduate Program in Biomedical Sciences Research and Innovation Department National School of Medicine and Health Sciences Tecnológico de Monterrey, México."
}
]
}
] | 1
|
https://f1000research.com/articles/10-1284
|
https://f1000research.com/articles/13-980/v1
|
29 Aug 24
|
{
"type": "Brief Report",
"title": "Altered coagulation profile of patients with high-grade glioma: clinical study with control group.",
"authors": [
"Natalia Jeanette Quispe-Pastor",
"Ana Paula Gorritti-Rubio",
"Lissett Jeanette Fernández-Rodríguez",
"Natalia Jeanette Quispe-Pastor",
"Ana Paula Gorritti-Rubio"
],
"abstract": "Background Activation of coagulation is a common phenomenon in patients with high-grade glioma, a primary malignant brain tumor.\n\nObjective Identify if there is an alteration in the coagulation profile in patients with high-grade glioma compared to other patients with benign brain tumors.\n\nMethods Sociodemographic and clinical characteristics, ECOG at admission, prothrombin time, activated partial thromboplastin time, international normalized ratio, platelet count, and blood panel results of 21 high-grade glioma patients (cases) and 42 meningioma patients (controls) from northern Peru were reviewed. Bivariate and multivariate analysis with logistic regression were performed to determine which factors are associated with glioma.\n\nResults Both groups had high proportions of high blood pressure (29%) and diabetes mellitus (14%). According to multivariate analysis, altered values for prothrombin time, platelet count, and ECOG score were associated with glioma (p=0.01). Furthermore, alterations in the blood panel were observed in both cases and controls but failed to reach statistical significance.\n\nConclusion Patients with high-grade glioma seem to suffer more from hypercoagulable states than other patients with benign brain tumors, suggesting careful vigilance and anticoagulant treatment for these patients.",
"keywords": [
"blood coagulation",
"glioma",
"platelet count",
"prothrombin time",
"meningioma"
],
"content": "Background\n\nGliomas are a class of primary brain tumors that arise from glial cells and generally have a poor prognosis.1 The malignancy of these tumors is classified into four grades, with grade four being the most malignant. High-grade gliomas (grades 3 and 4) are characterized by high mitotic activity, angiogenesis, as well as a predisposition to central necrosis, peripheral edema, rapid disease evolution, and mean survival between 12 and 17 months.1–3 Of these high-grade gliomas, the most common in adults are glioblastoma (grade 4), anaplastic astrocytoma, and anaplastic oligodendroglioma (both grade 3).4 The most common complication of high-grade gliomas is venous thromboembolism (VTE), with an incidence of approximately 30%.5\n\nVTE is a common complication found in many cancers that can be triggered directly by the tumor, such as overexpression of tissue factor (TF), or indirectly through host secretion of cytokines or physical alteration of blood vessels.6,7 Approximately 50% of patients with glioblastoma have background activation of the coagulation system.8 From this information, it is likely that understanding the clotting profiles of presurgical patients would be helpful in informing treatment with anticoagulants or determining prognosis based on coagulation profile. However, the judicious use of anticoagulants is important to not increase the risk of spontaneous intracerebral hemorrhage.\n\nDue to the aggressive nature of high-grade glioma and the risk of VTE, we set out to evaluate how the coagulation profile of these patients differs from other patients with brain cancer using a clinical study with a control group.\n\n\nMethods\n\nThis is an observational, descriptive, clinical study with a control group of a convenience sample of medical records.\n\nMedical records of both sexes were included if they were over 18 years old and diagnosed with high-grade glioma or meningioma and treated in the Virgen de la Puerta High Complexity Hospital Oncology Service (La Esperanza, Trujillo, Peru) between 2019 and 2023. Patients with an incomplete or absent anatomopathological study, and those with autoimmune or viral diseases, a history of coagulation disorders or diseases that affect blood circulation, brain metastases, or other primary tumors as well as patients receiving treatment with anticoagulant medications, were excluded from the study.\n\nThe medical records were reviewed to evaluate the presurgical hematological results of both controls and cases. These included hemogram (leukocytes, neutrophiles, band neutrophiles, lymphocytes, monocytes, eosinophiles, basophiles, red blood cell count, hemoglobin, and hematocrit) as well as coagulation profile (prothrombin time (PT), activated partial thromboplastin time (aPTT), international normalized ratio (INR), and platelet count (PC)). Each blood parameter was recorded as normal or abnormal.9 Additional sociodemographic and clinical characteristics were also recorded: age, sex, address, Eastern Cooperative Oncology Group (ECOG) performance status upon admission, and whether the patient had diabetes and/or high blood pressure.\n\nIBM SPSS V26.0 statistical software (https://www.ibm.com/es-es/products/spss-statistics) was used for data processing. An open-source alternative to this program is PSPP (https://www.gnu.org/software/pspp/). Qualitative variables were expressed in proportions and percentages of patients. Bivariate analysis was performed to determine the relationship of the variables. The crude odds ratio (ORc) and the adjusted odds ratio (ORa) were calculated with a 95% confidence interval (CI) for each variable in its association with the presence of high-grade glioma. Those variables that showed a significant association (p < 0.05) were subjected to multivariate analysis with logistic regression.\n\nThis study was reviewed and approved by the Research Bioethics Committee of Universidad Privada Antenor Orrego (Resolution N°0563-2023-UPAO), approval date 3rd August 2023. This study complied with the 2016 Council for International Organizations of Medical Sciences (CIOMS) guidelines. Given that this study was a review of medical records routinely collected during treatment, ensured patient privacy, and did not influence treatment trajectory, the requirement for informed consent was waived by ethical approval committee. Information that personally identifies patients was eliminated from the data presented here and underlying data to protect anonymity.\n\n\nResults\n\nThe sample consisted of 21 patients with high-grade glioma (cases) and 42 patients with meningiomas (controls) that met acceptance criteria. Patients with meningiomas were chosen as the control group as these tumors are benign, allowing for a close comparison of patients that had similar conditions – with the only difference being malignancy. All patients came from the Peruvian regions of La Libertad, Ancash, and Cajamarca. The demographic characteristics of both groups are summarized in Table 1. Ages were similar, but the gender ratio was reversed between cases and controls. ECOG scores were also distributed differently between cases and controls. Furthermore, both groups had high proportions of diabetes (14%) and high blood pressure (29%).\n\nTable 2 records the proportions of cases and controls with presurgical abnormal blood count and coagulation results. High proportions of abnormal results were found for aPTT, INR, lymphocytes, and neutrophiles.\n\nMultivariate analysis showed that PT (aOR = 1.45; 95% CI = 1.13 – 2.28; p = 0.01), PC (aOR = 1.43; 95% CI = 1.06 – 2.25; p = 0.01) and ECOG 2 or 3 (aOR = 14.78; 95% CI = 3.71 – 58.86; p = 0.01) were associated with said high-grade glioma (Table 3). Other components of the blood profile did not show significant differences between groups.\n\n\nDiscussion\n\nWe observe that PT was shortened in the cases compared to the controls. This result is consistent with two published studies using 58 cases and 22 meningioma controls8 and 172 cases and 47 healthy controls.10 The PT test evaluates the extrinsic coagulation pathway, which is initiated at the site of injury in response to the release of TF, which is often overexpressed in tumor cells. These results suggest that high-grade glioma is more likely to overexpress TF than other related cancers.8 Another parameter calculated from PT that evaluates the extrinsic coagulation pathway is INR. The difference in INR between cases and controls came close to (p=0.08), but did not reach statistical significance. This difference is likely a result of the use of different cutoff values for normal values, as INR is a ratio with PT in the numerator and a control PT in the denominator. Because PT was significantly shortened, INR also decreased, and another study comparing patients with healthy controls also found a statistically significant difference in these parameters,11 it would be reasonable to affirm that glioma patients have a more altered extrinsic clotting pathway compared to other patients with benign brain tumors and even more so when considering healthy controls.\n\nAnother parameter that was significantly associated with high-grade glioma was PC – no members of the control group had abnormal PC, while 4 patients in the case group had abnormal PC (Tables 2 and 3). Furthermore, cases of thrombocytosis and thrombocytopenia were observed in the case group. This result differs from previous investigations8,10 in which no statistically significant differences were found in PC between cases and controls were found (p>0.05). Small study size as well as differences in the timing of blood sample collection may explain the differences in these results with other studies.\n\nThe aPTT test is mainly used to evaluate the intrinsic coagulation pathway. In this study, no statistical significance was found between aPTT and the presence of glioma, with proportions of altered aPTT equal between cases and controls (Tables 2 and 3). This result differs from the findings of a study in which aPTT was shown to be significantly reduced in glioma cases, suggesting a hypercoagulable state.8\n\nBlood count can be used to assess general condition, detect disease-related complications, and, in some cases, predict survival in patients with high-grade glioma. In this study, alterations were observed in leukocytes, erythrocytes, hemoglobin, and hematocrit; however, no significant association with high-grade glioma was found in the multivariate analysis (Table 3). Navone et al. observed a significant increase in leukocyte count in glioblastoma patients compared to meningioma patients (p < 0.001), while hemoglobin did not show significant differences between the two study groups.8 On the other hand, Kim et al. assessed the clinical importance of lymphopenia in patients with glioblastoma and reported that 42.0% (92 patients) showed decreased levels of lymphocytes, concluding that lymphopenia is a frequent event during progression and disease treatment.12 In turn, Serban et al., when studying the preoperative immunoinflammatory status of patients with glioblastoma, found elevated leukocyte counts, suggesting that this could predict reduced overall survival.13\n\nFinally, multivariate analysis also identified that a preoperative ECOG score of 2 or 3 was significantly associated with high-grade glioma. However, no studies have been found to determine whether the ECOG value is related to glioma, so more research would be needed to determine the relationship between the two. However, in cancer patients, an ECOG 3-4 is associated with a higher risk of in-hospital mortality.14,15\n\nThis study presented certain limitations, such as limited sample size and scope since patients were not subjected to additional tests. Furthermore, it was not determined when the parameters of the coagulation profile were altered, so the study could not determine when a blood analysis would produce meaningful results.\n\n\nConclusions\n\nTaken together, it appears that high-grade glioma patients have hypercoagulability to a greater degree than patients with benign brain tumors and are more likely to be diagnosed when the disease interferes more strongly with their self-care and work activities. This suggests a more careful treatment of coagulation among these patients.\n\n\nCrediT author statement\n\nNJQP: Investigation, Writing – Original Draft\n\nAPGR: Supervision, Project administration\n\nLJFR: Conceptualization, Writing – Review & Editing",
"appendix": "Data availability statement\n\nFigshare. Underlying Data for article “Altered coagulation profile of patients with high-grade glioma: clinical study with control group”. https://doi.org/10.6084/m9.figshare.26391244. 16\n\nThis project contains following dataset:\n\n• Data File 1: Coagulacion-raw-data-eng.xlsx\n\n• Data File 2: STROBE checklist for ‘Altered coagulation profile of patients with high-grade glioma: case-control study’\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nWang LM, Englander ZK, Miller ML, et al.: Malignant Glioma.Rezaei N, Hanaei S, editors. Human Brain and Spinal Cord Tumors: From Bench to Bedside Volume 2: The Path to Bedside Management. Cham: Springer International Publishing; 2023 [cited 2024 Mar 16]; pp. 1–30. Publisher Full Text\n\nMorey RJR, Ramírez-Morfa CA, Rivero-Morey J: Tratamiento del glioma cerebral de alto grado en el paciente adulto. Universidad Médica Pinareña. 2020 Jan 9 [cited 2024 Mar 16]; 16(1): 389. Reference Source\n\nCortés AS, Crespo MEO: Calidad de vida en pacientes con tumores cerebrales: importancia de las variables psicológicas. Clínica y Salud. 2015 Feb 23 [cited 2024 Mar 16]; 26(1): 23–32. Publisher Full Text Reference Source\n\nMéndez-Aguilar P, Vera-Ponce VJ, Méndez-Aguilar P, et al.: Factores pronóstico de supervivencia en adultos por gliomas de alto grado en un Hospital de Lima, Perú. Revista de la Facultad de Medicina Humana. 2020 Jul [cited 2024 Mar 16]; 20(3): 460–471. Publisher Full Text Reference Source\n\nEisele A, Seystahl K, Rushing EJ, et al.: Venous thromboembolic events in glioblastoma patients: An epidemiological study. Eur. J. Neurol. 2022 Aug [cited 2024 Mar 16]; 29(8): 2386–2397. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSosa-Quintero LS, Carrasco-Martínez IL, Mariscal-Ramírez I, et al.: El estado protrombótico en los pacientes con cáncer. GAMO. 2021 Jun 15 [cited 2024 Mar 16]; 20(1): 5369. Publisher Full Text Reference Source\n\nAy C, Pabinger I, Cohen AT: Cancer-associated venous thromboembolism: Burden, mechanisms, and management. Thromb. Haemost. 2017 Jan 26; 117(2): 219–230. PubMed Abstract | Publisher Full Text\n\nNavone SE, Guarnaccia L, Locatelli M, et al.: Significance and Prognostic Value of The Coagulation Profile in Patients with Glioblastoma: Implications for Personalized Therapy. World Neurosurg. 2019 Jan; 121: e621–e629. PubMed Abstract | Publisher Full Text\n\nHall JE: Guyton and Hall Textbook of Medical Physiology. 13th ed.Philadelphia, PA: Saunders; 2015; 1168.\n\nLi W, Wang YR, Song W, et al.: The changes of plasma coagulation function in patients with glioma and its correlation with malignant grade of glioma. Zhonghua Yi Xue Za Zhi. 2018 Jan 30; 98(5): 336–339. PubMed Abstract | Publisher Full Text\n\nUnsal E, Atalay F, Atikcan S, et al.: Prognostic significance of hemostatic parameters in patients with lung cancer. Respir. Med. 2004 Feb; 98(2): 93–98. PubMed Abstract | Publisher Full Text\n\nKim WJ, Dho YS, Ock CY, et al.: Clinical observation of lymphopenia in patients with newly diagnosed glioblastoma. J. Neuro-Oncol. 2019 Jun; 143(2): 321–328. PubMed Abstract | Publisher Full Text\n\nSerban GM, Tamas CI, Tamas F, et al.: Preoperative Immune-Inflammatory Status of the Patients With Newly-Diagnosed Glioblastoma - Could It Genuinely Predict Their Survival? Cureus. 2023 Aug; 15(8): e43802. PubMed Abstract | Publisher Full Text\n\nPérez Cruz P, Acevedo Claros FN: Escalas de Estado Funcional (o performance satus) en Cáncer. Gastroenterología Latinoamericana. 2014 [cited 2024 Mar 16]; 25(3): 219–226. Reference Source\n\nDíaz-Díaz D, Villanova Martínez M, Palencia Herrejón E: Pacientes oncológicos ingresados en Unidad de Cuidados Intensivos. Análisis de factores predictivos de mortalidad. Med. Intensiva. 2018 Aug 1 [cited 2024 Mar 16]; 42(6): 346–353. PubMed Abstract | Publisher Full Text Reference Source\n\nQuispe-Pastor NJ, Gorritti-Rubio AP, Fernandez L: Underlying Data for article “Altered coagulation profile of patients with high-grade glioma: clinical study with control group”. figshare. 2024, 28 Temmuz. Publisher Full Text"
}
|
[
{
"id": "320124",
"date": "16 Sep 2024",
"name": "Darko Orešković",
"expertise": [
"Reviewer Expertise Neurosurgery",
"neuro-oncology"
],
"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 important and currently overlooked issue in treating neuro-oncological patients and I applaud the authors for their work writing this brief report.\n\nTheir objective is clear and their methods are sound. Also, the discussion is relevant and important.\n\nHowever I would add several suggestions.\nFirst of all, I think the authors should acknowledge the fact that they only analyzed coagulation markers in two groups of patients with brain tumors. Both of these tumors are known to cause perturbations in the coagulation profile. A control group without a malignant disease, whose results would be compared to these two groups would be much better. I would like this fact to be emphasized more in the limitations of the study (if not changed in the study design).\n\nSecondly, a major limitation is the fact that the authors do not know when the blood samples were taken. This is important because various conditions, diseases and therapy can also impact the coagulation profile. For example, our own previous research analyzes the connection between corticosteroid treatment and the coagulation profile in these patients (Oreskovic et al 2024.). This limitation also has to be emphasized more.\n\nThirdly, I would like to see additional references showing the effects of altered PT on the risk of VTE, especially in brain tumor patients. In other words, what are the clinical implications of the found results.\n\nLastly, it is true that the coagulation patterns of brain tumor patients are important in light of VTE risk. However, they are also very important due to the fact that parts of the coagulation cascade have a crucial role in the development and aggressiveness of glial tumors (Magnus et a. 2013). This should also be acknowledged.\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? I 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": "12699",
"date": "31 Oct 2024",
"name": "Lissett Fernández",
"role": "Author Response",
"response": "Thank you for this review. I have replied to your comments and explained the changes to the article in a point-by-point manner. The comments are preceded by “>>” This is an important and currently overlooked issue in treating neuro-oncological patients and I applaud the authors for their work writing this brief report. Their objective is clear and their methods are sound. Also, the discussion is relevant and important. However I would add several suggestions. First of all, I think the authors should acknowledge the fact that they only analyzed coagulation markers in two groups of patients with brain tumors. Both of these tumors are known to cause perturbations in the coagulation profile. A control group without a malignant disease, whose results would be compared to these two groups would be much better. I would like this fact to be emphasized more in the limitations of the study (if not changed in the study design). >> The authors agree that it is important to make clear the natures of the study and control group. Therefore, additional text was added to the introduction and the limitations paragraph explaining the reason for the use of the control group. This article was designed to highlight the uniquely pro-coagulatory effects of high-grade gliomas with respect to non-malignant brain neoplasms. This means that we are likely underestimating the coagulatory dysfunction in glioblastoma patients with respect to healthy, cancer-free people. Secondly, a major limitation is the fact that the authors do not know when the blood samples were taken. This is important because various conditions, diseases and therapy can also impact the coagulation profile. For example, our own previous research analyzes the connection between corticosteroid treatment and the coagulation profile in these patients (Oreskovic et al 2024.). This limitation also has to be emphasized more. >> We have made the text clear in the limitations paragraph that therapy could have had an impact in the coagulation profile. Patients with diseases that affect coagulation were excluded from the study as mentioned in the methods section. Thirdly, I would like to see additional references showing the effects of altered PT on the risk of VTE, especially in brain tumor patients. In other words, what are the clinical implications of the found results. >> A paragraph explaining the implications and the effects of altered PT on the risk of VTE was added. This additional paragraph has several references that are relevant to the topic. Lastly, it is true that the coagulation patterns of brain tumor patients are important in light of VTE risk. However, they are also very important due to the fact that parts of the coagulation cascade have a crucial role in the development and aggressiveness of glial tumors (Magnus et a. 2013). This should also be acknowledged. >> Additional text and references in the introduction and discussion were added to make this point in the article."
}
]
},
{
"id": "324060",
"date": "24 Sep 2024",
"name": "Joab Chapman",
"expertise": [
"Reviewer Expertise Neuroimmunology",
"neuro-coagulation",
"neuroinflammation"
],
"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 solid addition to the data associating high grade glioma with systemic coagulation changes.\nMajor comments Introduction: Secretion of thrombin and other active coagulation factors by gliomas is well known and excess thrombin may thus reach venous blood in the brain and cause venous thrombosis. This central mechanism should be added to the Introduction and perhaps Discussion. This mechanism seems highly relevant to the coagulation measures described in the manuscript.\n\nMethods and Results: The statistical methods used to compare the groups are not clear to me. Some of the measures are quantitative (PT, aPTT etc) and though they are categorized into normal and pathological in tables 1 and 2, it is not clear if the analysis presented in table 3 was performed on continuous or categorical data. It would probably be more informative if performed on the continuous quantitative data. Analysis of INR would perhaps be significant in such and analysis. Bivariate analysis is usually performed on continuous data. It is also not clear (to me) what the OR represent. The authors state in the opening of the Discussion that \" We observe that PT was shortened in the cases compared to the controls\" but it is difficult to understand if the values were higher or lower in the Results. Using the values of tests such as PC would enable us to assess if the pathology associated with glioma are high or low values, so presenting the data as mean + error would be more informative.\nMinor comments ECOG not defined in the abstract (Eastern Cooperative Oncology Group performance status). Study design: not clear what \"convenience sample\" means.\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? 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? Yes",
"responses": [
{
"c_id": "12698",
"date": "31 Oct 2024",
"name": "Lissett Fernández",
"role": "Author Response",
"response": "Thank you for this review. I have replied to your comments and explained the changes to the article in a point-by-point manner. The comments are preceded by “>>” This is a solid addition to the data associating high grade glioma with systemic coagulation changes. Major comments Introduction: Secretion of thrombin and other active coagulation factors by gliomas is well known and excess thrombin may thus reach venous blood in the brain and cause venous thrombosis. This central mechanism should be added to the Introduction and perhaps Discussion. This mechanism seems highly relevant to the coagulation measures described in the manuscript. >> The authors added statements in the introduction and the discussion explaining the mechanism. Methods and Results: The statistical methods used to compare the groups are not clear to me. Some of the measures are quantitative (PT, aPTT etc) and though they are categorized into normal and pathological in tables 1 and 2, it is not clear if the analysis presented in table 3 was performed on continuous or categorical data. >> We modified the text to make it clear whether a categorical or quantitative variable was used. It would probably be more informative if performed on the continuous quantitative data. Analysis of INR would perhaps be significant in such and analysis. Bivariate analysis is usually performed on continuous data. It is also not clear (to me) what the OR represent. >> We dichotomized the data because most clinical practice considers values as either normal or abnormal. However, additional text was added explaining direct analysis of the continuous quantitiative data in the Results and the Discussion section. >> A short explanation of what OR represents was added to the Methods and the Results section. The authors state in the opening of the Discussion that \" We observe that PT was shortened in the cases compared to the controls\" but it is difficult to understand if the values were higher or lower in the Results. Using the values of tests such as PC would enable us to assess if the pathology associated with glioma are high or low values, so presenting the data as mean + error would be more informative. >> The direction of the difference was added, so it is clear what parameters increased or decreased in the study group compared to the control group. >> Additional text was added to the Results and the Discussion sections to include analysis and explanation of the direction of change as well as direct statistical analysis of the continuous results. Minor comments ECOG not defined in the abstract (Eastern Cooperative Oncology Group performance status). >> The term was appropriately defined in the abstract. Study design: not clear what \"convenience sample\" means. >> The term was removed from the text."
}
]
}
] | 1
|
https://f1000research.com/articles/13-980
|
https://f1000research.com/articles/12-559/v1
|
30 May 23
|
{
"type": "Research Article",
"title": "Whole body vibration and rider comfort determination of an electric two-wheeler test rig",
"authors": [
"Keerthan Krishna",
"Sriharsha Hegde",
"Mahesha G T",
"Satish Shenoy B",
"Keerthan Krishna",
"Sriharsha Hegde",
"Mahesha G T"
],
"abstract": "Background: Two-wheeled vehicles are the major mode of transportation in India. Such vehicles are exposed to excessive vibration on the road when compared to four-wheeled vehicles. However, the research on the reduction of whole body vibration in the case of two-wheelers is not explored in detail. The present study predicts rider comfort in the case of an electric two-wheeler as per ISO 2631-1. Methods: An electric two-wheeler test rig is used in the study. The values of acceleration from the test rig in running conditions are obtained by using NI LabVIEW 2016. The drive cycle of the electric vehicle (EV) test rig is controlled by Sync sols’ EV lab software. Obtaining the root mean square (RMS) acceleration from running the test setup, it is compared with the ISO 2631 standard to obtain the rider comfort. Results: Loading area, traction motor, base mount, and suspension were found to be the strategic points of vibration. RMS acceleration of 0.2 g to 3.29 g obtained at these points are prone to cause discomfort for the rider. Vehicle speed, road profile, and duration of exposure were found to be important parameters affecting the rider’s comfort. About 19 % increase in the vibration amplitude is observed at the loading area when loads are removed. The loading area as corresponds to a rider’s seat in actual vehicle, it is important to reduce these vibrations to make the ride comfortable for the rider. Conclusions: A suitable damping technique design is very much essential in reducing these vibrations and improve the rider comfort, as many more non-deterministic vibrations are prone to cause dis-comfort in case of actual on road riding conditions.",
"keywords": [
"Electric Two-wheeler",
"Rider comfort",
"Whole-body vibration",
"RMS Acceleration",
"Road profile"
],
"content": "Introduction\n\nIn India, the major mode of transportation is two-wheeled vehicles.1 About 15 million two-wheeled vehicles were sold in India over the last 10 years on yearly basis.2 Professionals like the food and goods delivery partners, low-wage employees, and post-delivery persons mainly use two-wheelers for their daily transportation.3 Two-wheeled vehicles, owing to limited size and mass are prone to vibration when compared to four-wheeled vehicles.4 Whole-body vibration (WBV) mainly affects these people who are in continuous exposure to noise and vibration throughout the day.5,6 Truck drivers, drill operators, heavy machinery workers, and forklift drivers are the victims of these vibrations.7 High risks of lower back pain, motion sickness, and digestive system problems have been reported due to WBV when exposed for a longer period.8,9\n\nThe whole body vibration of the vehicle is dangerous not only to the rider but also to the vehicle as well.10 In a vehicle exposed to different terrain conditions, the driving scenario is subjected to vibration, and these are transmitted to the human body through the seat, handlebar, and footrest in the case of two-wheelers.11 These vibrations transferred to the human body cause different health issues in long run.12,13 Some researchers are working on reducing these vibrations to effectively increase rider comfort.14–17\n\nA vehicle's comfort is influenced by many factors such as the seat design,18 driving posture19 and environmental factors,20 road condition, and suspension system to name a few. In a two-wheeler, the rider’s comfort plays a very important role, as the rider has continuous exposure to these influencing factors. Both the static and dynamic condition of the vehicle are important in predicting the rider’s comfort.21 Different kinds of shock absorbers,22 and damping techniques23 play a vital role in improving the rider’s comfort. Two-wheelers especially in the Indian scenario are very much subjected to vibration due to the condition of roads even in the cities.24 The comfort level is greatly influenced by potholes, humps, cracks, and riding speed, and some study work has assisted in recognizing the potholes for safe driving.25\n\nThe measurement of whole-body vibration in terms of human health and comfort, perception probabilities, and motion sickness occurrence is studied with the help of ISO 2631-1 standard.26 It provides guidance on measurement techniques for periodic, random, and transient whole-body vibrations.27 By getting the Frequency Response Function (FRF) at critical vibrational points, variable acceleration values at multiple spots were identified. The rider's comfort depends on these values of acceleration. The higher the value of acceleration lowers the rider's comfort. ISO 2631-1 standard provides different levels of comfort faced by riders depending on the acceleration values. Table 1 gives the detailed classification of the rider’s comfort level as per ISO 2631-1.\n\nThe present study involves finding the strategic locations of vibration and evaluation of rider comfort on an electric two-wheeler (E2W) test rig. Different points at the test rig are evaluated for their acceleration values in different running conditions. The points (locations on the body of test rig) at which the amplitude of vibration is higher than other locations are considered strategic points of vibration. The vibration at the strategic points is high enough to cause discomfort to the rider. The impact hammer test29 is conducted using the PCB (Pico Coulomb) Piezotronics made impact hammer of sensitivity 10.1 mV/g and data acquisition by using NI LabVIEW.\n\n\nMethods\n\nThe electric two-wheeler test rig is modeled as a state space model for finding its natural frequencies. Performing the impact hammer test on the setup, the natural frequencies are obtained. The details of the work carried out are discussed in this section.\n\nTest setup\n\nThe test setup is an electric vehicle two-wheeler test rig, which uses a 1.5 kW, brushless direct current (BLDC) traction motor powered by a 25AH LiFePO4 battery. Figure 1 shows the photograph of different parts of the Electric two-wheeler (E2W) test rig (components sourced from Artis Technologies) and Table 2 gives the nomenclature.\n\nUsing the laboratory's setup, the E2W test rig is modeled as state space model.30 However, to build a similar model, two considerations were made, which are briefly discussed here. The first thing to consider is the cylindrical steel roller of approximately 40 mm diameter and 200 mm in length beneath the test rig's wheel is used to simulate a real-life road surface. The roller used is a hard plastic material In this case, however, unlike the road and wheel, the roller causes a small vertical displacement to the wheel. As a consequence, the vertical displacement of the roller concerning the vertical displacement of sprung and un-sprung masses is estimated to be near zero or zero.31,32 The second subject of consideration concerns the sprung and un-sprung masses. Sprung mass is the percentage of the vehicle's overall mass that is supported by the suspension. Un-sprung mass refers to the mass of the suspension, wheels, and other components that are directly connected to them. This implies that a vehicle's sprung mass is typically the vehicle's kerb weight, the weight of the driver, and in certain cases, the weight of the engine.33 A state space model of the E2W test rig is shown in Figure 2.34 The model nomenclature is indicated in Table 3. The acceleration values are measured by the PCB Piezotronics made accelerometers of 101.1 mV/g sensitivity and data acquisition is carried out through National Instrument’s LabVIEW software. (MyOpenLab is an open source alternative that can carry out a similar function). Three trials were conducted and the average values are considered for analysis.\n\nThe free body and Laplace equations of the state space model derived are as indicated below in equations 1, 2 and 3, 4 respectively:\n\nLaplace equations\n\nFigure 2 shows the state space model of the E2W test rig and the corresponding notations as indicated in the figure.\n\nFigure 3 shows the magnitude vs frequency plots of the impact hammer test conducted on the E2W test rig. The plot obtained from the NI LabVIEW, 2016 ((MyOpenLab is an open source alternative that can carry out a similar function). shows the natural frequency of the test rig as obtained at two strategic points on the test rig ash shown in Figure 3. The peaks in the graphs indicated the natural frequency of the rig. The average of the natural frequency obtained is shown in Table 4.\n\nNational Instruments’ LabVIEW 2016 (64-bit) software is used to extract the acceleration values (MyOpenLab is an open source alternative that can carry out a similar function). To obtain the rider’s comfort as per ISO 2631 standard,26 the raw acceleration is converted to RMS acceleration using the spectral analysis function in the LabVIEW software. Some open-source software like MyOpenLab can be used for data acquisition and spectral analysis as well. Fast Fourier transform (FFT)35 is used to obtain the root mean square acceleration values at the strategic locations.\n\nThe test setup is tested under different loading conditions, namely. kerb load, 5 kg load, and 10 kg load. This type of loading makes a machine or a material get stiffer as the load increases.36 PCB Piezotronics made accelerometers are mounted at four strategic locations of vibration; the loading area, traction motor, suspension and the base mount of the rig. RMS acceleration, at these strategic locations, is recorded using LabVIEW programming. These values are then compared with ISO 2631 standard to analyze the rider’s comfort.\n\nDrive cycle\n\nThe drive cycle used for the study is shown in Figure 4. Different scenarios like idling, acceleration, steady speed, and deceleration are shown in the graph. The drive cycle runs each of these scenarios for a particular time duration. The cycle begins with a preparation speed-up period of 5 seconds, followed by 20 seconds of idling, 18 seconds of acceleration, and 2 seconds of steady speed. The cycle then decelerates for the next 11 seconds, a combination of acceleration and steady speed for the next 7 seconds, decelerates for the next 30 seconds, idles for the next 11 seconds, and ends with 3 seconds of halting. The values of acceleration are recorded at the strategic locations during this cycle.\n\n\nResults and discussion\n\nIn this study, major strategic locations of vibrations in an electric two-wheeler test rig are found. These values are then compared with the ISO 2631-1 standard to further analyze the rider comfort. In conducting the impact hammer test, initially, the natural frequency was extracted. Further, by building a state space model of the test rig and running the setup in different driving scenarios the RMS acceleration was obtained at the strategic locations. A detailed discussion of the result obtained is provided in this section.37\n\nThe acceleration values obtained at the strategic locations of vibration show that the values of RMS acceleration are in the range of 0.2 g to 3.2 g when the whole setup is considered. The strategic locations obtained are, the loading area of the rig, the traction motor, the suspension, and the base mount of the rig. These locations when checked for their vibration characteristics provide the vibration intensity. The values of acceleration obtained, when compared with ISO 2631-1 guideline gives the rider comfort in the vehicle as shown in Table 1.\n\nFigure 5, shown below indicates the different values of acceleration at the strategic locations of vibration. Observing, the RMS acceleration it is seen that, the rider comfort ranges from fairly- uncomfortable region to extremely uncomfortable region as compared to Table 1. These values indicate that there is a lot of scope for improving the rider's comfort. Comparing Figures 4 and 5 it is observed that, as the speed increases the vibration intensity increases as well.\n\nObserving the RMS acceleration at the loading area, the value of g increases as the speed increases. During idling, the no-load acceleration of 3.29g is recorded at the loading area which is higher compared to the loaded accelerations of 0.16g. The values of RMS acceleration increase with acceleration and decrease with deceleration. As the load is increased from 0 to 10 kg, the values of acceleration decrease. This is due to the un-damped fixture of the loading area.37 The values obtained are extremely uncomfortable for the rider and need the researcher’s attention in damping the vibrations. The vibration at the traction motor indicates that the amplitude of vibration is in the range of 0.21g to 0.25g and this falls under the category of very uncomfortable region. The suspension and the base mount show vibrations in the range of 0.48g to 1.308g and are in the region of the extremely uncomfortable and very uncomfortable region respectively.\n\n\nConclusions\n\nA detailed experimental analysis of finding the strategic locations of vibration is discussed in this paper. The acceleration values play an important role in deciding the rider’s comfort. Electric two-wheeler, even though a cost-effective mode of transportation, require further research in improving rider comfort. Different strategic locations of vibration are found to affect the rider’s comfort. The following conclusions are drawn from this study:\n\nLoading area, traction motor, base mount, and suspension were found to be the strategic points of vibration in the E2W test rig. About a 19% increase in the vibration can be observed in the loading area when the loads are removed. This loading area corresponds to the seat of the driver in an actual vehicle and is prone to huge vibration and thus needs attention in damping these vibrations. The acceleration at other strategic locations is found to be higher at loading as well as no-load conditions and these vibrations induce discomfort to the rider as well.\n\nAs the speed increases, the vibration intensity increased as well. This is due to the wheels running on the roller support, which simulates an actual road scenario. Hence, it can be concluded that in the actual driving scenario of a two-wheeler the vibration increases as the speed of the vehicle is increased. Further, the condition of the road is again an influencing factor, which increases the vibration intensity.\n\nOverall study indicates that the electric two-wheeler is subjected to vibrations is an important area to be considered for further research work and this can be reduced by using suitable damping techniques at the strategic locations of vibrations.",
"appendix": "Data availability\n\nFigshare: data for paper submitted to f1000 research. https://doi.org/10.6084/m9.figshare.22092101.v1. 38\n\nThis project contains the following underlying data:\n\n‐ 5kg raw data fig 4.xlsx (RMS acceleration for 5kg loading)\n\n‐ 10kg raw data fig 4.xlsx (RMS acceleration for 10kg loading)\n\n‐ Down left back fig 3e.xlsx (Impact hammer test data at base mount at back side left)\n\n‐ Down left front fig 3g.xlsx (Impact hammer test data at base mount at front side left).\n\n‐ Down right back fig 3f.xlsx (Impact hammer test data at base mount at back side right).\n\n‐ Down right front fig 3g.xlsx (Impact hammer test data at base mount at front side right).\n\n‐ No load raw data fig 4.xlsx (RMS acceleration for No load condition).\n\n‐ Raw Data for fig 5.lvm (RMS acceleration obtained at strategic locations).\n\n‐ Top left back fig 3c.xlsx (Impact hammer test data at loading area at back side left).\n\n‐ Top right back fig 3b.xlsx (Impact hammer test data at loading area at back side right).\n\n‐ Top right front 3d.xlsx (Impact hammer test data at loading area at front side right).\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\nI. T. S. (iTrans) and N. D. Pvt. Ltd., TBIU, IIT Delhi, “Two Ͳ and Ͳ Three Ͳ Wheelers in India,” no. June.2009. Reference Source\n\nStatista: Two-wheeler domestic sales in India from from financial year 2011 to 2021(in million units).2021. Reference Source\n\nPaper W: the Power of Digitalizing the Power of Digitalizing.2022. Reference Source\n\nNaveen Kumar C, Rajkumar G, Sethubalan B, et al.: Measurement of vibration in different parts of the two wheeler and its harmfulness to human body. Int. J. Mech. Prod. Eng. Res. Dev. 2018; vol. 8(7): pp. 493–501.\n\nParvez M, Khan AA, Bhardwaj S: Muscular Discomfort in Occupational Motorcycle Riding. Singapore: Springer; 2021.\n\nParvez M, Khan AA: Prediction of ride comfort of two-wheeler riders exposed to whole-body vibration. Singapore: Springer; 2019.\n\nKumar R, Sharma R, Kumar V, et al.: Predictors of Whole-Body Vibration Exposure among Indian Bus and Truck Drivers. J. Phys. Conf. Ser. 1854; 1854: 012033. Publisher Full Text\n\nSingh A, Singh I, Kalsi S: Transmissibility Evaluation of Whole-Body Vibration Using Three-Layer Human CAD Model. J. Inst. Eng. Ser. C. 2020; 101(3): 595–602. Publisher Full Text\n\nTiemessen IJH, Hulshof CTJ: Low back pain in drivers exposed to whole body vibration: analysis of a dose – response pattern.2008. Publisher Full Text\n\nBorse PA, Desale DPS: Effect of Motor Vehicle Structural Vibration on Human Body – Review. Iarjset. 2017; 4(7): 145–149. Publisher Full Text\n\nMulla L, Khuba P, Dhere A, et al.: Extraction of vibration behavior in conventional and electric drive two-wheeler using order analysis. IOP Conf. Ser. Mater. Sci. Eng. 2019; 624(1): 012009. Publisher Full Text\n\nSerrano-Fernández MJ, Boada-Grau J, Robert-Sentís L, et al.: Predictive variables for musculoskeletal problems in professional drivers. J. Transp. Health. 2019; 14(June): 100576. Publisher Full Text\n\nRaffler N, Ellegast R, Kraus T, et al.: Factors affecting the perception of whole-body vibration of occupational drivers: an analysis of posture and manual materials handling and musculoskeletal disorders. Ergonomics. 2016; 59(1): 48–60. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSivakumar A, Tiwari A, Raghvendra G, et al.: Elastomer blend for vibration isolators to meet vehicle key on - Key off vibrations and durability. SAE Tech. Pap. 2010. Publisher Full Text\n\nKhune S, Bhende A: Vibration analysis of motorcycle handlebar for riding comfort using tuned mass damper. J. Meas. Eng. 2020; 8(4): 142–152. Publisher Full Text\n\nTathavadekar P, Liu KJ, Rajan S, et al.: Application of tuned mass damper to address discrete excitation away from primary resonance frequency of a structure. SAE Tech. Pap. 2009; 4970. Publisher Full Text\n\nFasana A, Giorcelli E: A vibration absorber for motorcycle handles. Meccanica. 2010; 45(1): 79–88. Publisher Full Text\n\nIftekhar H, et al.: Study of comfort performance of novel car seat design for long drive. Proc. Inst. Mech. Eng. Part D J. Automob. Eng. 2020; 234(2–3): 645–651. Publisher Full Text\n\nPark J, Jung K, Chang J, et al.: Evaluation of driving posture prediction in digital human simulation using RAMSIS®. Proc. Hum. Factors Ergon. Soc. 2011; 55(September): 1711–1715. Publisher Full Text\n\nLin TP, Hwang RL, Huang KT, et al.: Passenger thermal perceptions, thermal comfort requirements, and adaptations in short- and long-haul vehicles. Int. J. Biometeorol. 2010; 54(3): 221–230. PubMed Abstract | Publisher Full Text\n\nVelagapudi SP, Ray GG: The Influence of Static Factors on Seating Comfort of Motorcycles: An Initial Investigation. Hum. Factors. 2020; 62(1): 55–63. PubMed Abstract | Publisher Full Text\n\nAyas H, Ahmed J: Analysis Of Damping Force Of Two Wheeler Front Suspension.2013; 2(6): 428–434.\n\nMangaraju KV, Govardan D, Chavan C, et al.: PAPER SERIES SAE 2008-32-0068 JSAE 20084768 Optimization of Damping Characteristics for Two Wheelers.2008; (724).\n\nAlam P, Ahmad K, Afsar SS, et al.: Study of vibrations produced on five different types of flyovers in Delhi, India. Int. J. Struct. Eng. 2015; 6(4): 318–331. Publisher Full Text\n\nNarmada M, Munaswamy P: Indication of pothole on roads for safety driving. Int. J. Innov. Technol. Explor. Eng. 2019; 8(8): 964–966.\n\nISO: ISO 2631-1.pdf.1997.\n\nI. O. for Standardisation: International Organisation for Standardisation (ISO): ISO 2631-1 Mechanical vibration and shock – Evaluation of human exposure to whole-body vibration – part 1: general requirements.1997; pp. 1–31. Reference Source\n\nISO 2631-1: International Standard Iso 2631-1.1997; vol. 1997, pp. 1–28. Reference Source\n\nAy AM, Wang Y, Khoo S: Signal processing for time domain analysis of impact hammer test data. 8th Eur. Work. Struct. Heal. Monit. EWSHM. 2016; 1: 628–637.\n\nDesikan A, Kalaichelvi V: Design for a semi-active preview suspension system using fuzzy-logic control and image processing techniques. 2015 IEEE Int. Conf. Cyber Technol. Autom. Control Intell. Syst. IEEE-CYBER 2015. 2015; (October): pp. 191–196. Publisher Full Text\n\nTürkay S, Akçay H: A study of random vibration characteristics of the quarter-car model. J. Sound Vib. 2005; 282(1–2): 111–124. Publisher Full Text\n\nKulkarni A, Ranjha SA, Kapoor A: A quarter-car suspension model for dynamic evaluations of an in-wheel electric vehicle. Proc. Inst. Mech. Eng. Part D J. Automob. Eng. 2018; 232(9): 1139–1148. Publisher Full Text\n\nThite AN: Development of a refined quarter car model for the analysis of discomfort due to vibration. Adv. Acoust. Vib. 2012; 2012: 1–7. Publisher Full Text\n\nDongardive AA, Bhosale OB, Shelke GD, et al.: Development and validation of linear and non-linear model of passive suspension system. 7th Natl. Conf. Recent Dev. Mech. Eng. RDME-2018. 2018; 12(1): 24–29. Reference Source\n\nFahy K: Fast Fourier Transforms and Power Spectra in LabVIEW ®. Transform. 1993; (February): 1–18.\n\nHockett JE, Gillis PP: Mechanical testing machine stiffness. Part I-Theory and calculations. Int. J. Mech. Sci. 1971; 13(3): 251–264. Publisher Full Text\n\nRepetto CE, Roatta A, Welti RJ: Forced vibrations of a cantilever beam. Eur. J. Phys. 2012; 33(5): 1187–1195. Publisher Full Text\n\nKrishna K, Dr. Shenoy S , Mahesha GT, et al.: Data for paper submitted to f1000 research. [Data]. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "187826",
"date": "24 Jul 2023",
"name": "Peter Múčka",
"expertise": [
"Reviewer Expertise Vibration",
"vehicle dynamics",
"signal processing"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe work is not clearly and accurately presented. It cites the current literature.\nThe academic merit of the work is low.\nThe novelty of the work is limited. This is the report from vibration measurement.\nDetails of methods and analysis provided do not allow replication by others. The interpretation of results is confused (the measured values are not comparable in principle with ISO 2631-1 comfort reaction levels).\nIn my opinion the work does not offer the novel or important results.\nGeneral comments:\n1. ISO 2631-1 does not specify impact hammer test approach. Please clarify.\n2. Page 3 – Methods COMMENT: State-space representation is a mathematical model of a physical system related by first-order (not involving second derivatives) differential equations. The used quarter-car model (Fig. 2) for two-wheeler test rig is described by differential equations involving second derivative. Clarify.\n3. Authors measured the acceleration at two-wheeled test rig. It is not clear why the quarter-car model (Fig. 2), equations of motions (1-4) and Table 3 Test rig model nomenclature are used in the paper. I did not see any results connected with them.\n4. Page 7 “Obtaining acceleration using LabVIEW“ COMMENT: This approach should be connected and explained with definitions in ISO 2631-1. Where is the measuring point? ISO 2631-1 specified the likely reactions of passengers in public transport. Where is passenger in your case?\n5. Page 8 “These values are then compared with the ISO 2631-1 standard to further analyze the rider comfort.” COMMENT: ISO 2631-1 is specified for standing, sitting and recumbent persons. ISO 2631 used the frequency-weighted acceleration. Clarify.\n6. Page 8 – Comparison of measured acceleration values at the test rig with comfort level criteria based on frequency-weighted acceleration measured at sitting, standing or recumbent persons is not correct.\n7. The results are not compared with observations and results of other authors. What is the impact of such results?\nSpecific comments:\nPage 3 – “By getting the Frequency Response Function (FRF) at critical vibrational points, variable acceleration values at multiple spots were identified” COMMENT: ISO 2631-1 did not specify this approach for acceleration identification. Clarify.\nPage 3. “Table 1 gives the detailed classification of the rider’s comfort level as per ISO 2631-1.” COMMENT: Specify how acceleration was estimated in line with ISO 2631-1: 1997. Annex C.2.3 Comfort reactions to vibration environments in ISO 2631-1 specified magnitudes of overall vibration total values.\nPage 5 – Eq. (2) COMMENT: In Eq. (2) the variable x is used for kinematic excitation (vertical excitation of the rolller) but the Fig. 2 used the variable U.\nPage 5, Table 2 COMMENT: C (Ns/m) is not damping ratio but damping coefficient. Is this ok? “M1 Un-sprung mass (tyre mass) – (kg)”. I assume, the first dof (X1) ist he roller mass (undamped) vibration and the second dof (X2) is tyre mass (damped) vibration. Please clarify.\n\nPage 6, Figure 3 COMMENT: The Scheme of Impact hammer test on E2W test rig (cases a) to h) may be visualized. It is not clear what is “loading area” and what is “base mount”.\nPage 7 \"The values of acceleration are recorded at the strategic locations during this cycle.“ COMMENT: Where are these strategic locations? Clarify.\nPage 7 COMMENT: Add the scheme of location of PCB Piezotronics accelerometers.\nPage 7 “Table 4. Average of natural frequencies.” COMMENT: Natural frequencies of what system? Match the natural frequencies to the particular parts of analysed mechanical system.\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?\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": "10132",
"date": "25 Sep 2023",
"name": "Satish Shenoy B",
"role": "Author Response",
"response": "We are very grateful for the reviewer’s comments and all the necessary changes have been incorporated in the manuscript. Please note all the comments are addressed in the paper and highlighted for reference. Peter Múčka, Slovak Academy of Sciences, Bratislava, Slovakia General comments: 1. ISO 2631-1 does not specify impact hammer test approach. Please clarify. Answer: Impact hammer test was conducted in order to check if any operating frequencies co-inside with the natural frequency of the system. Accordingly, one of the natural frequencies (180Hz) was found to near to the natural frequency of the system and the relation has been mentioned and updated in the conclusions. 2. Page 3 – Methods COMMENT: State-space representation is a mathematical model of a physical system related by first-order (not involving second derivatives) differential equations. The used quarter-car model (Fig. 2) for two-wheeler test rig is described by differential equations involving second derivative. Clarify. Answer: Here the equations 1 & 2 are the governing system equations and later derived Laplace equations (3 & 4) represent the state space equations. The detail explanation is again added and updated to the manuscript. 3. Authors measured the acceleration at two-wheeled test rig. It is not clear why the quarter-car model (Fig. 2), equations of motions (1-4) and Table 3 Test rig model nomenclature are used in the paper. I did not see any results connected with them. Answer: The equations 1 to 4 are derived to show the system mathematically and this is basic study conducted on the test rig. The research has continued considering an actual vehicle and converting the ICE vehicle to Electric as well. Understanding the quarter car model of the test rig is important in understanding the dynamics of the system. 4. Page 7 “Obtaining acceleration using LabVIEW“ COMMENT: This approach should be connected and explained with definitions in ISO 2631-1. Where is the measuring point? ISO 2631-1 specified the likely reactions of passengers in public transport. Where is passenger in your case? Answer: Strategic locations have been indicated and have been updated in the version 2 of the paper. However, ISO 2631 standard is compared in this paper against the RMS acceleration obtained at the strategic locations. As these strategic locations especially the loading area corresponds to the rider’s seat in an actual two-wheeler, this standard has been used. Further, this study is continued in an actual two-wheeler considering an actual rider and road interactions. Which is the future scope of the this paper. 5. Page 8 “These values are then compared with the ISO 2631-1 standard to further analyze the rider comfort.” COMMENT: ISO 2631-1 is specified for standing, sitting and recumbent persons. ISO 2631 used the frequency-weighted acceleration. Clarify. Answer: Here ISO 2631 is compared with the RMS acceleration obtained at the strategic locations of vibration. As these strategic locations especially the loading area corresponds to the rider’s seat in an actual two-wheeler, this standard has been used. 6. Page 8 – Comparison of measured acceleration values at the test rig with comfort level criteria based on frequency-weighted acceleration measured at sitting, standing or recumbent persons is not correct. Answer: Frequency weightings not considered in this paper. This paper only compares the RMS acceleration to determine the peak amplitudes in the test rig. Frequency weightings and calculations of Vibration dose value is the future scope of this paper. 7. The results are not compared with observations and results of other authors. What is the impact of such results? Answer: We have not come across such results from literatures. These results taken from accelerometers in an electric two-wheeler test rig and these results are unique. Specific comments: Page 3 – “By getting the Frequency Response Function (FRF) at critical vibrational points, variable acceleration values at multiple spots were identified” COMMENT: ISO 2631-1 did not specify this approach for acceleration identification. Clarify. Answer: Conducting FRF is a process conducted using NI’s LabVIEW software. This is conducted in order to convert the raw acceleration obtained to RMS acceleration at the strategic locations. Obtaining RMS acceleration, later these values are compared with ISO 2631 as mentioned in the standard. ISO 2631 specifies comfort categories based on RMS acceleration, and only this part of the standard is being compared with the results obtained. Page 3. “Table 1 gives the detailed classification of the rider’s comfort level as per ISO 2631-1.” COMMENT: Specify how acceleration was estimated in line with ISO 2631-1: 1997. Annex C.2.3 Comfort reactions to vibration environments in ISO 2631-1 specified magnitudes of overall vibration total values. Answer: These have been added in the version 2 adding RMS accelerations which signifies the overall vibration total values as specified by the standard. Page 5 – Eq. (2) COMMENT: In Eq. (2) the variable x is used for kinematic excitation (vertical excitation of the rolller) but the Fig. 2 used the variable U. Answer: These variables are identified and rectified at both the locations. The roller excitation is indicated as U. Page 5, Table 2 COMMENT: C (Ns/m) is not damping ratio but damping coefficient. Is this ok? “M1 Un-sprung mass (tyre mass) – (kg)”. I assume, the first dof (X1) is the roller mass (undamped) vibration and the second dof (X2) is tyre mass (damped) vibration. Please clarify. Answer: The variable name is identified and rectified. C is damping coefficient. Here X1 is the vertical displacement of mass M1 and X2 is the vertical displacement of Mass M2. Page 6, Figure 3 COMMENT: The Scheme of Impact hammer test on E2W test rig (cases a) to h) may be visualized. It is not clear what is “loading area” and what is “base mount”. Answer: The strategic locations i.e. loading area, traction motor, suspension and base mount are updated in figure 1 in version 2 of the paper. Page 7 \"The values of acceleration are recorded at the strategic locations during this cycle.“ COMMENT: Where are these strategic locations? Clarify. Answer: The strategic locations are as shown in figure 1 (loading area, traction motor, suspension and base mount). Page 7 COMMENT: Add the scheme of location of PCB Piezotronics accelerometers. Answer: Scheme of location of PCB Piezotronics accelerometers are added to the paper and highlighted for reference. Page 7 “Table 4. Average of natural frequencies.” COMMENT: Natural frequencies of what system? Match the natural frequencies to the particular parts of analysed mechanical system. Answer: Here the natural frequencies shown are of the entire electric two-wheeler test rig. The frequency is matched with particular part in version 2 of the paper."
}
]
},
{
"id": "187825",
"date": "16 Aug 2023",
"name": "Le Van Quynh",
"expertise": [
"Reviewer Expertise Vibration Analysis",
"Nonlinear Dynamic Structural",
"Vibration Modal"
],
"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 your work and the paper submitted. There is a lot of work presented and I would suggest some revisions to improve the quality of the paper\nMost of the analysis results, the authors only reconstructed considering the value analysis on the time domain based on ISO 2631-1 standard, but did not analyze the frequency domain, especially the low frequency domain. Therefore, the goal of smooth analysis is not vehicle ride comfort. I advise the authors to correct and add to clarify.\n\nPage 4: The author shows the measuring positions in Fig.1.\n\nPage 5: Eq.(1)- E(4) have not been found to be related to the experimental results, please review?\n\nPage 8: the y axis representation of Fig.5 is the acceleration values, not RMS acceleration values, please review?\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": "10133",
"date": "25 Sep 2023",
"name": "Satish Shenoy B",
"role": "Author Response",
"response": "We are very grateful for the reviewer’s comments and all the necessary changes have been incorporated in the manuscript. Please note all the comments are addressed in the paper and highlighted for reference. 2. Le Van Quynh, Automotive and Power Machinery Engineering, Thai Nguyen University of Technology, Thai Nguyen City, Vietnam General comments: Most of the analysis results, the authors only reconstructed considering the value analysis on the time domain based on ISO 2631-1 standard, but did not analyze the frequency domain, especially the low frequency domain. Therefore, the goal of smooth analysis is not vehicle ride comfort. I advise the authors to correct and add to clarify. Answer: The graphs and plots showing frequency domain have been added to the paper (Figure 5) and explained. Page 4: The author shows the measuring positions in Fig.1. Answer: All the positions along with strategic locations have been updated in the figure. Page 5: Eq.(1)- E(4) have not been found to be related to the experimental results, please review? Answer: Here the equations 1 & 2 are the governing system equations and later derived Laplace equations (3 & 4) represent the state space equations. The detail explanation is again added to the manuscript. Page 8: the y axis representation of Fig.5 is the acceleration values, not RMS acceleration values, please review? Answer: RMS acceleration have been indicated and it is updated in version 2 of the paper."
}
]
}
] | 1
|
https://f1000research.com/articles/12-559
|
https://f1000research.com/articles/13-1300/v1
|
30 Oct 24
|
{
"type": "Case Report",
"title": "Case Report: Unmasked: Deceptive pediatric spinal meningioma",
"authors": [
"Maroua Slouma",
"Sameh Achoura",
"Samar Zarati",
"Kais Bouzouita",
"Ridha Chekili",
"Karima Tlili",
"Imen Gharsallah",
"Maroua Slouma",
"Sameh Achoura",
"Kais Bouzouita",
"Ridha Chekili",
"Karima Tlili",
"Imen Gharsallah"
],
"abstract": "Introduction Pediatric meningiomas are rare tumors originating from the meninges’ arachnoid cap cells, representing a small fraction of all meningiomas. The clinical presentation of pediatric meningiomas varies widely depending on their location within the central nervous system. We report a case of pediatric spinal meningioma revealed by gait disturbance. We emphasize clinical and imaging features, as well as therapeutic management of spinal meningiomas.\n\nCase presentation We present the case of a 15-year-old boy with a one-year history of chronic thoracic back pain, worsening gait disturbances, and difficulty walking. Neurological examination revealed a spastic gait with increased muscle tone and bilateral pyramidal syndrome. Magnetic resonance imaging (MRI) demonstrated a posterior intradural extramedullary mass at the T6-T7 level, causing dorsal spinal cord compression. The patient underwent complete resection of the tumor, and histological examination confirmed the diagnosis of a WHO grade I psammomatous spinal meningioma.\n\nConclusion This case highlights the clinical and imaging characteristics of spinal meningiomas in pediatric patients. MRI remains the gold standard for diagnostic imaging, effectively narrowing down differential diagnoses. However, a definitive diagnosis requires histological examination. The primary therapeutic approach for pediatric meningiomas is surgical resection.",
"keywords": [
"Spinal meningioma",
"pediatric meningioma",
"back pain",
"gait disturbance"
],
"content": "Highlights\n\n\n\n1. Spinal pediatric meningiomas are rare and can mimic various conditions, making diagnosis particularly challenging.\n\n2. MRI plays a crucial role in differentiating between potential diagnoses. However, histopathological confirmation is essential for diagnosing meningiomas and guiding appropriate management.\n\n3. Detailed history, thorough physical examination, and genetic screening are crucial to rule out associations with genetic conditions, particularly NF2, which necessitates a different management approach and genetic counseling.\n\n4. Surgery aiming for total tumor resection is the first-line treatment for spinal pediatric meningiomas. Unfortunately, the post-operative course in this population is often complicated by higher recurrence rates and additional complications.\n\n\nIntroduction\n\nGait abnormalities are common in children and can result from various conditions, including cerebral palsy, neuromuscular disorders, and spinal cord tumors, such as spinal meningiomas. Spinal meningiomas account for less than 10% of central nervous system tumors in the pediatric population.1\n\nPediatric meningiomas (PMs) are an even rarer entity, accounting for less than 5% of all meningiomas, and spinal PMs are estimated to be exceedingly rare.2\n\nSpinal meningiomas are characterized by their intradural, extramedullary growth,1 often resulting in a mass effect on the spinal cord that can lead to significant spinal cord compression and related complications.3\n\nThe management of pediatric meningiomas is challenging, with a higher incidence of preoperative and postoperative complications.3,4 Surgical resection remains the first-line treatment, similar to adult cases. On the other hand, radiotherapy (RT) is considered on a case-by-case basis due to its potential risks in the pediatric population although it is often required, particularly in NF2-associated cases, where tumors are more aggressive and recurrent.3,4\n\nWe report a case of pediatric spinal meningioma revealed by gait disturbance. We emphasize clinical and imaging features, as well as therapeutic management of spinal meningiomas.\n\n\nCase presentation\n\nA 15-year-old male presented with a one-year history of progressively worsening back pain, described as dull, persistent, and localized to the thoracic spine. The pain had an insidious onset and was non-radiating. The patient also reported an unsteady gait, difficulty ambulating, and lower extremity weakness, limiting his walking distance to approximately 100 meters. He denied any history of trauma, fever, malignancy, bowel or bladder dysfunction, seizures, or headaches. Family history was unremarkable, with no known cases of neurofibromatosis, malignancy, Gorlin syndrome, or familial meningiomatosis.\n\nOn physical examination, the patient exhibited a gait disturbance with increased muscle tone, though muscle strength testing was within normal limits. Neurological examination revealed abolition of abdominal cutaneous reflexes, bilateral symmetric hyperreflexia in the lower limbs, and a positive Babinski sign. No pain was elicited upon percussion of the spinous processes. He had no meningeal signs, spinal limitation, or arthritis.\n\nCardiovascular and pulmonary examinations were unremarkable, and no cutaneous lesions were noted.\n\nC-reactive protein, calcium level, liver tests, and renal function were within normal ranges. The complete blood count was without abnormalities.\n\nGiven the presence of neurological signs, a spine MRI was performed showing a posterior intradural mass at the T6 and T7 vertebral levels, characterized by an extramedullary, well-circumscribed, homogeneous, and lobulated appearance. The lesion measured approximately 1.8 × 1.2 × 0.9 cm and exhibited iso-intensity on T1-weighted images and hyperintensity on T2-weighted images, with homogeneous and marked enhancement after contrast administration. The mass exerted a local mass effect, resulting in dorsal spinal cord compression. These findings were initially suggestive of a thoracic glioma, with differential diagnoses including low-grade ependymoma or astrocytoma [Figure 1a, 1c].\n\nThe patient underwent posterior spinal surgery, including a wide laminectomy spanning T5, T6, and T7. Upon opening the dura mater, a whitish, firm mass compressing the adjacent spinal cord was observed. The tumor displayed a well-defined cleavage plane with the dura mater, with only minor adhesions to the adjacent arachnoid. Complete resection of the tumor was achieved.\n\nHistopathological examination revealed a proliferation of meningothelial cells with poorly defined cytoplasmic borders, creating a syncytial appearance and exhibiting cytological pleomorphism. Numerous psammoma bodies were observed throughout the specimen, with no evidence of anaplasia or tumor necrosis [Figure 1b]. These findings were consistent with a WHO Grade 1 psammomatous meningioma.\n\nUnfortunately, the postoperative course was complicated by the onset of hyperalgesic back pain two months later, along with the development of dorsal hyperkyphosis [Figure 1d]. This complication was attributed to the extensive laminectomy. A posterior thoracic arthrodesis was performed [Figure 1e]. The patient is currently undergoing motor rehabilitation with favorable clinical progress.\n\n\nDiscussion\n\nWe present the case of a pediatric spinal meningioma revealed by an insidious onset of gait disturbance, thoracic back pain, and lower limb weakness. Meningiomas are typically slow-growing tumors originating from the meninges.3\n\nSimilarly to intracranial meningiomas, spinal meningiomas arise from arachnoid cap cells. Abnormal proliferation of these cells leads to the formation of intradural extramedullary masses. Spinal meningiomas represent 5 to 10% of all meningiomas and constitute 25 to 45% of all intraspinal tumors.1,2 Spinal meningioma typically occurs in the thoracic spine since arachnoid cap cells are predominantly located at this spinal level.3,4\n\nPediatric meningiomas are scarce, accounting for less than 5% of pediatric spinal tumors, and an even a smaller fraction of overall pediatric meningiomas.2\n\nUnlike in adults, pediatric meningiomas seem to be less influenced by hormonal factors, which may explain the similar gender distribution observed in this population.2–4\n\nMeningiomas are graded by the World Health Organization (WHO) into three grades based on their histological features, such as mitotic rate, cellular atypia, and brain invasion. Grade I meningiomas are benign characterized by a low mitotic rate (<4 per 10 high-power fields) and the absence of brain invasion, and include a psammomatous subtype,4 as seen in our patient. The same grading system applies to PMs.\n\nIn contrast to adults, an association between pediatric meningiomas and type 2 neurofibromatosis (NF2) has been reported in 13% of cases and even in more than 50% of patients with intracranial meningiomas.5\n\nThe NF2 gene mutation is responsible for abnormal cell proliferation and tumor formation.\n\nNF2-related meningiomas are characterized by an earlier onset, more rapid growth, atypical histological features, and higher WHO grades (II and III).2–5\n\nPediatric meningiomas may also be associated with other genetic syndromes, such as Gorlin syndrome (basal cell nevus syndrome) and familial meningiomatosis. However, our patient had no personal or family history of these conditions. In a study of CT scans from 82 patients with Gorlin syndrome, 5% showed radiological features suggestive of meningioma.6\n\nSpinal meningiomas are characterized by their intradural, extramedullary growth, typically affecting the thoracic spine,3,4 as seen in our patient. While asymptomatic spinal meningiomas usually exhibit a slow, linear growth pattern, symptomatic tumors are prone to an exponentially accelerating growth rate,3 leading to varying degrees of spinal cord compression, ranging from insidious motor and sensory dysfunction to gait disturbances, and difficulty walking as observed in our patient. Symptoms generally worsen progressively over time as the tumor continues to expand, exerting increased pressure on the spinal cord. In advanced stages, severe spinal cord compression can disrupt autonomic functions, resulting in bowel and bladder disturbances, which are reported in approximately 36% of patients, and irreversible neurological damage.2–3 Chronic cases often present with persistent back pain, as was evident in our patient, which may be associated with radiculopathy or evolve into a more debilitating condition. Longstanding tumor presence can also contribute to spinal deformities, such as kyphosis.3\n\nIn addition, both pediatric and adult meningiomas share similar basic MRI features, such as a well-circumscribed, intradural extramedullary location, the characteristic dural tail sign, and comparable signal intensities on T1- and T2-weighted images. However, spinal pediatric meningiomas tend to exhibit more aggressive patterns. Indeed, they may appear larger at diagnosis, involve longer spinal segments, and cause more significant compression of the spinal cord compared to those in adults.1–4\n\nUpon clinical presentation and examination, distinguishing pediatric spinal meningiomas from other etiologies is challenging due to their ability to mimic various conditions. In this case, the patient’s insidious gait disturbances and progressive lower body weakness raised clinical suspicion of spinal cord compression. Both the patient and family denied any recent trauma, and the physical examination showed no signs of bruising.\n\nNeoplastic etiologies are among the most frequent causes of spinal cord compression in the pediatric population, commonly involving ependymomas, astrocytomas, gliomas, and meningiomas. Clinically, distinguishing between these neoplasms is often impossible. MRI is crucial for differential diagnosis and guiding surgical planning, Although definitive diagnosis relies on histopathological examination for accurate confirmation and management.\n\nContrary to spinal meningiomas, which are typically extramedullary, these tumors have an intramedullary growth pattern. Therefore, the characteristic “dural tail sign”,3,4,6 an enhancement extending along the dura adjacent to the tumor on post-contrast images, is absent in intramedullary tumors.\n\nGliomas and astrocytomas typically present with poorly defined margins, often involving multiple spinal segments and causing spinal cord expansion, in contrast to the well-defined and circumscribed appearance of meningiomas. Ependymomas, although intramedullary-like gliomas, are also well-defined and circumscribed, often featuring a “cap sign” on T2-weighted images, corresponding to a rim of hemosiderin. A cystic component and syringomyelia can be associated with ependymomas, which is a distinguishing feature from meningiomas.7\n\nTethered cord syndrome can mimic spinal meningioma due to gait abnormalities and progressive motor dysfunction of the lower limbs. However, no foot deformities or cutaneous markers such as sacral dimples, lipomas, or hairy patches along the midline of the back were observed on examination. MRI ruled out this diagnosis, as it did not reveal a low-lying conus medullaris, thickened filum terminal, or evidence of spinal cord tension.8\n\nGiven the presentation of spasticity, lower limb weakness, and hyperreflexia, spinal meningioma could also be mistaken for transverse myelitis, which accounts for 20% of spinal cord compression cases in the pediatric population, most commonly occurring between 10 and 19 years of age. However, the absence of a rapid onset over hours to days and the lack of sensory or autonomic dysfunctions made this diagnosis less likely in our patient. Moreover, MRI did not demonstrate the characteristic spinal cord lesions of transverse myelitis, and laboratory results were within normal ranges.9\n\nManagement of meningioma is largely dependent on its symptomatic status.3 Asymptomatic meningiomas can often be managed with routine observation and imaging.3,4\n\nConversely, symptomatic and rapidly enlarging meningiomas, typically require surgical resection as the primary approach.3,4\n\nComplete surgical excision of meningiomas is the gold standard.2–4\n\nAdjuvant radiotherapy (RT) may be recommended, in cases of recurrent tumors, non-resectable, growing lesions, or when gross total resection is not achievable.3,4 However, RT is generally avoided in pediatric patients due to the heightened risk of secondary malignancies and long-term neurocognitive sequelae.2–5\n\nUnfortunately, the postoperative course in pediatric patients is marked by a higher incidence of spinal instability, especially following extensive laminectomies,2–4,10 necessitating spinal fusion or stabilization procedures, as was required in our patient.\n\nRecently, emerging surgical techniques, such as endoscopic endonasal approaches, are being investigated for the resection of midline anterior skull base tumors, offering a minimally invasive alternative.4\n\nTo date, novel pharmacotherapies, including multikinase inhibitors targeting vascular endothelial growth factor receptors and bevacizumab, have shown promising results; however, consensus guidelines have yet to be established.10 Interestingly, radionuclide therapies targeting somatostatin receptors are under exploration for the management of refractory meningiomas, demonstrating great potential.10\n\nRegular follow-ups with MRI are recommended every 6 months for the first 5 years post-treatment, followed by annual assessment.3,4,10\n\n\nConclusion\n\nThe diagnosis of spinal tumors should be considered in children with gait disturbances.\n\nPediatric meningiomas present with a spectrum of symptoms, ranging from back pain to severe spinal cord compression and even spinal deformities. MRI typically shows a well-defined and circumscribed extramedullary appearance with the characteristic dural tail sign on post-contrast images. A total resection is considered the gold standard. Radiotherapy is reserved for specific scenarios, including recurrence, subtotal resection, inoperability, or high-grade tumors.\n\n\nEthical considerations\n\nConsent: Written informed consent for publication of their clinical details was obtained from the patient’s legal guardians.",
"appendix": "Data availability statement\n\nNo data are associated with this article.\n\n\nReferences\n\nHsu W, Jallo GI: Pediatric spinal tumors. Handb. Clin. Neurol. 2013; 112: 959–965. Publisher Full Text\n\nKotecha RS, Pascoe EM, Rushing EJ, et al.: Meningiomas in children and adolescents: a meta-analysis of individual patient data. Lancet Oncol. 2011; 12(13): 1229–1239. PubMed Abstract | Publisher Full Text\n\nBuerki RA, Horbinski CM, Kruser T, et al.: An overview of meningiomas. Future Oncol. 2018; 14(21): 2161–2177. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGoldbrunner R, Stavrinou P, Jenkinson MD, et al.: EANO guideline on the diagnosis and management of meningiomas. Neuro-Oncology. 2021; 23(11): 1821–1834. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOpoku I, Yang L, Sun P, et al.: Pediatric Cerebral Meningioma: A Single-Center Study with 10 Children Not Associated with Neurofibromatosis Type 2 and Literature Review. Pediatr. Neurosurg. 2022; 57(6): 422–433. PubMed Abstract | Publisher Full Text\n\nUdaka YT, Packer RJ: Pediatric Brain Tumors. Neurol. Clin. 2018; 36(3): 533–556. Publisher Full Text\n\nRudà R, Bruno F, Pellerino A, et al.: Ependymoma: Evaluation and Management Updates. Curr. Oncol. Rep. 2022; 24(8): 985–993. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKobets AJ, Oliver J, Cohen A, et al.: Split cord malformation and tethered cord syndrome: case series with long-term follow-up and literature review. Childs Nerv. Syst. 2021; 37(4): 1301–1306. PubMed Abstract | Publisher Full Text\n\nGrasso EA, Pozzilli V, Tomassini V: Transverse myelitis in children and adults. Handb. Clin. Neurol. 2023; 196: 101–117. Publisher Full Text\n\nMair MJ, Berghoff AS, Brastianos PK, et al.: Emerging systemic treatment options in meningioma. J. Neuro-Oncol. 2023; 161(2): 245–258. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "361312",
"date": "04 Feb 2025",
"name": "Kautilya R Patel",
"expertise": [
"Reviewer Expertise Vascular neurosurgery and skull base neurosurgery"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis is a good case description of a pediatric spinal meningioma, which is not seen commonly. A 15 year old child with compressive myelopathy due to an intradural extramedullary lesion at T6-T7 level was managed successfully with surgical resection. Patient developed postoperative kyphosis due to extensive laminectomy and required surgical stabilization. It is supported with a good discussion of pediatric meningiomas.\nThe following concerns could be addressed to improve the overall presentation. 1. Timeline of development of symptoms other than pain could be described for a clearer picture of temporal evolution of clinical symptoms. 2. Modified Ashworth grade of lower limb spasticity can be specified at preoperative stage and at follow-up. Details related to posterior column involvement would enhance the clinical examination details. 3. Meningiomas have a typical appearance on MRI and can be diagnosed quite confidently based on an MRI. It is not very challenging with MRI widely available. Of course, it is not a common diagnosis in this age group. 4. The MRI findings described in the text can be supported with the relevant MRI sequences in axial plane. Moreover, the laterality of the lesion could be described. The described findings are typical for a meningioma, and are not suggestive for a glioma/ependymoma/astrocytoma which are typically intramedullary lesions. 5. Surgical treatment is not specifically very challenging even in this age group. References 3 and 4 do not support the statement \"The management of pediatric meningiomas is challenging, with a higher incidence of preoperative and postoperative complications.\" in Introduction. 6. A smaller laminectomy probably restricted to one level (T6) with undermining of T5 and T7 levels or a hemilaminectomy or laminoplasty would have possibly prevented the postoperative kyphosis especially in a young patient as in this case. This could be included in the discussion section. 7. Clinical condition at follow-up can be described more objectively. Follow-up MRI imaging to demonstrate the surgical outcome is essential. 8. Transverse myelitis does not cause spinal cord compression. It involves a segment of spinal cord itself. 9. Endoscopic endonasal approaches are not relevant to this case discussion as they deal with intracranial meningiomas. 10. Discussion can be made concise and focus on discussion pertaining to pediatric spinal meningiomas. It can be organised into sections focusing on pathogenesis, clinical presentation and differentials, management and long term concerns.\n\nOverall, it is a good case description but can be improved further.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1300
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https://f1000research.com/articles/13-816/v1
|
19 Jul 24
|
{
"type": "Research Article",
"title": "Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film",
"authors": [
"Aji Sukoco",
"Yukihiro Yamamoto",
"Hiroyuki Harada",
"Atsushi Hashimoto",
"Tomoyuki Yoshino",
"Aji Sukoco",
"Hiroyuki Harada",
"Atsushi Hashimoto",
"Tomoyuki Yoshino"
],
"abstract": "Background The utilization of zein and gum arabic has grown in an attempt to formulate wall materials based on protein–polysaccharide complexes. This mixture provides a versatile shelter for hydrophilic (guava leaf extract, GLE) or lipophilic (fish oil, FO) bioactive compounds from unwanted environmental factors, and it can be used as an edible film-forming polymer. This study was undertaken to characterize FO-containing edible films that were double-layered with a film containing GLE.\n\nMethods Modified zein and gum arabic solutions (MG complex) were mixed at a ratio of 1:1.5 (v/v), adjusted to pH 5, added with glycerol (20% of the complex) and FO (5% of the complex), and finally adjusted to pH 5. This was prepared as the bottom/lower layer. The upper/active layer was prepared by mixing MG complex, glycerol, and GLE (1, 3, and 5% w/v of the complex). Physical, mechanical, microstructural, thermal, microbiological, and oxidative measurements were also performed.\n\nResults The total phenolic and flavonoid contents in GLE were 15.81 mg GAE/g extract and 6.99 mg QE/g extract, respectively. The IC50 of the DPPH radical scavenging activity of GLE was 26.86 ppm with antibacterial activity against Bacillus subtilis and Escherichia coli of 9.83 and 12.55 mm. The total plate counts of films double-layered with a film containing GLE were retained below 3 log CFU/g during 28-day storage. The peroxide values of these films were dimmed for no more than 9.08 meq/kg sample on day 28 of storage. Thickness (872.00-971.67 μm), water vapor transmission rate (12.99-17.04 g/m2/day), tensile strength (1.56-2.02 kPa), elongation at break (61.53-75.41%), glass transition (52.74-57.50°C), melting peak (131.59-142.35°C), inhibition against B. subtilis (33.67-40.58 mm), and inhibition against E. coli (2.05-9.04 mm) were obtained by double-layer films.\n\nConclusions GLE can be successfully incorporated into the active layer of a double-layer film to improve its characteristics while significantly slowing down the microbial contamination and oxidation rate.",
"keywords": [
"Antibacterial",
"antioxidant",
"double-layer",
"edible film",
"fish oil",
"guava leaf extract",
"gum Arabic",
"zein"
],
"content": "Introduction\n\nFish oil (FO) is a precious source of bioactive lipids such as omega-3 fatty acids, which can improve numerous health functions. Previous studies have demonstrated the positive impact of FO consumption on the health and brain development of children.1–3 In the context of alleviating the risk of disease, FO has been investigated to mitigate fracture, cardiovascular, colorectal, prostate, and chronic kidney disorders in people over the age of 50.4–8 Therefore, a wide utilization of FO is not limited to dietary supplements. Enrichment of FO in solid to liquid food products, such as dark chocolate,9 cookies,10 granola bars,11 sausage,12 milk chocolate,13 and yogurt14 has also been attempted. However, owing to the high content of omega-3 fatty acids, the oxidative stability of FO in food products can be compromised. Despite encapsulation-stabilized FO, oxidation remains a challenge because the direct incorporation of encapsulated FO may affect the stability of its wall materials during food processing, allowing interaction with food ingredients and external factors. The latter can exaggerate the simultaneous oxidation reaction that leads to the rejection of food products owing to off-flavors.\n\nAn alternative to enriching food with FO has been established in previous studies through the preparation of edible films containing FO alone or in combination with essential oils.15–18 They found that FO alone could increase the elongation of the film, and the combination of essential oils dampened the oxidation rate. Edible film is the outer part of the food matrix, and air is the most influential factor in the oxidation process that directly interacts with the film. Thus, a double-layered film can be proposed to minimize the oxidation of FO in the matrix of the edible film. A multilayer design can enhance the functionality of the packaging outstrip mono-layered design.19 In this study, the first (lower) layer was made from edible film solution containing FO only, and the edible film solution for the second (upper) layer was incorporated with active compounds only.\n\nIn addition to essential oils, plant extracts can be used to strengthen the upper/active layer. Several previous studies have investigated the combination of fish oil and apple peel extract,20 cashew leaf extract,21 and green tea extract.22 Among other plant-based sources of active compounds, guava (Psidium guajava) leaves have been widely exploited as a popular natural remedy in traditional medicine. Secondary metabolites derived from leaves provide excellent antioxidant and antimicrobial activities,23 making them a valuable (high bioactivity, abundance, and low price) part of agricultural waste. Thus, guava leaf extract (GLE) is a suitable candidate for protecting edible films rich in FO.\n\nThe selection of film-forming polymers is also a crucial step for the successful implementation of this idea. Protein-polysaccharide complexes have been developed for the preparation of edible films and the encapsulation of FO. Gum arabic (GA) can be used as a polysaccharide in edible films because it is safe to use as an emulsifying and stabilizing agent in food processing. They are also abundantly available and inexpensive. Because poor water vapor resistance and high brittleness are the main shortcomings of GA-based film,24 it requires an additional ingredient that can reinforce their barrier and mechanical properties. Zein is a plant protein derived from corn that has good biocompatibility and biodegradability. Zein contains more than 50% hydrophobic amino acids,25 it is useful to improve the characteristics of edible films. Simultaneously, FO can be stabilized by the hydrophobic amino acids of zein. Peppermint oil, medium-chain triglyceride oil, and resveratrol have been successfully protected using a wall material based on a zein-GA mixture.26–28 To the best of our knowledge, no reports have documented the combination of zein and GA as polymers for the preparation of double-layer edible films, in which one layer contains FO and the other contains GLE. Therefore, this study was performed to evaluate the physical, mechanical, microstructural, thermal, microbiological, and oxidative properties of FO-containing edible films double-layered with a film containing GLE.\n\n\nMethods\n\nFish oil was purchased from Tama Biochemical Co. Ltd. (Tokyo, Japan). Guava leaves were collected from the tertiary and secondary branches of guava trees aged four years. The guava trees were cultivated by local farmers in Banyuwangi, Indonesia. Pure zein powder, gum arabic powder, glycerol, sodium dodecyl sulfate, sodium carbonate, aluminum nitrate, potassium acetate, calcium chloride, potassium chloride, potassium iodide, gallic acid monohydrate, quercetin dihydrate, ascorbic acid, sodium thiosulfate, isooctane, isopropanol, methanol, and acetic acid were obtained from Fujifilm Wako (Osaka, Japan). 1,1-Diphenyl-2-picrylhydrazyl (DPPH) was purchased from TCI Chemical Trading Co., Ltd. (Tokyo, Japan). Folin-Ciocalteu reagent was acquired from Kanto Chemical Co. Inc. (Tokyo, Japan). Tryptic soy agar (TSA) (Bacto™, Maryland, USA), peptone (Bacto™, Maryland, USA), 6 mm paper discs (ADVANTEC, Tokyo, Japan), Escherichia coli NBRC 3972 (Tokyo, Japan), and Bacillus subtilis JCM 20094 (Ibaraki, Japan) were used for microbiological analysis. Filter paper 5C (185 mm) (ADVANTEC, Tokyo, Japan) and membrane filter 1.0 μm (Millipore, Ireland) were used for the extraction process. Filter paper 2 (90 mm) (ADVANTEC, Tokyo, Japan) was used for the filtration process in the analysis of peroxide values. Ultrapure water (Type 1) was used in this study.\n\nIn this study, GLE was prepared using water as a solvent. Fresh leaves were washed and dried in an oven at 60°C for approximately 48 h. The leaves were then ground and sieved through a 60-mesh sieve to obtain a fine guava leaf powder (moisture content of 10.13%). A weighed powder (50 g) was dissolved in 500 mL of water. The mixture was stirred at 1100 rpm for 60 min at 70°C. It was then filtered using filter paper (185 mm). The supernatant was subsequently filtered using a vacuum filtration apparatus (SIBATA, Japan) equipped with a membrane filter 1.0 μm which removed fine impurities and large-sized bacteria. Water was evaporated for 3 h at 60°C using a rotary evaporator to concentrate the extract from 1 to 25 °Brix. The GLE was stored in a refrigerator (4°C).\n\nThe total phenolic content was determined using the Folin-Ciocalteu method, as described by Kim et al.29 with modifications. Serial concentrations (10, 20, 30, and 40 μg/mL) of gallic acid standard were prepared from a stock standard solution of 1000 μg/mL. A volume (500 μL) of each concentration was added to 500 μL of Folin–Ciocalteu phenol reagent. The mixture was then shaken and incubated for 8 min. Subsequently, 4 mL 7.5% sodium carbonate was added to the mixture and vigorously shaken using a vortex. Approximately 10 mL of water was then added. Incubation was performed for 60 min at 24±2°C in the dark. Absorbance was measured at 730 nm using a UV-Vis spectrophotometer (Hitachi U-2900, Japan). A calibration curve was established based on the absorbance against serial concentrations. This procedure was also used to measure the sample (extract) solution at a concentration of 1000 μg/mL. The total phenolic content was expressed as milligrams of gallic acid equivalents per gram of extract (mg GAE/g extract).\n\nThe total flavonoid content was analyzed according to Otsuka et al.30 with slight modifications. A quercetin standard solution (1000 μg/mL) was prepared to obtain serial concentrations (2.5, 5, 10, 20, 40, and 80 μg/mL) of the standard. Water (1.5 mL) was transferred to 500 μL of each concentration, and 100 μL of 10% aluminum nitrate was subsequently added. A volume (100 μL) of 1M potassium acetate was added to the mixture. A new mixture was incubated in the dark for 40 min at 24±2°C. The absorbance of 1 mL of the mixture was measured at 450 nm using a UV-Vis spectrophotometer (Hitachi U-2900, Japan). Measurement of the total flavonoid content of the extract (1000 μg/mL) was performed using the same procedure. The results were expressed as milligrams of quercetin equivalents per gram of extract (mg QE/g extract).\n\nDPPH radical scavenging activity was assayed using the method described by Brand-Williams et al.31 with modifications. DPPH solution (0.1 mM) was prepared using methanol. The extract was prepared at concentrations of 1000 μg/mL and serial concentrations (20, 60, 100, 140, and 180 μg/mL) were then made. Two milliliters of each concentration were mixed with 2 mL of DPPH solution and incubated for 30 min in the dark at 24±2°C. The absorbance was then measured at 517 nm using a UV-Vis spectrophotometer (Hitachi U-2900, Japan). Ascorbic acid (AA) was used as the standard at concentrations of 2, 4, 6, 8, and 10 μg/mL. Antioxidant activity was expressed as the IC50 value (ppm). It was calculated from the % inhibition curve, and the AA standard was used for comparison.\n\nAn agar disc diffusion test was conducted to determine the antibacterial activities of GLE and edible films against B. subtilis and E. coli. Briefly, an aliquot (100 μL) of a suspension of B. subtilis (107 CFU/mL) or E. coli (106 CFU/mL) was evenly spread onto solid TSA medium. One hundred microliters of GLE at several concentrations (25, 50, 75, and 100%) were dropped onto a sterile paper disc with a diameter of 6 mm. The discs were allowed to dry for 10 min in a sterile glass Petri dish and then placed on the inoculated media. The edible film samples were cut to a size of 6×6 mm. The dishes were incubated for 48 h at 30°C. The diameter was measured in millimeters using a digital caliper (Niigata Seiki SK DT-150, Japan).\n\nA zein solution (5%, w/w) was prepared from pure zein powder in aqueous acetic acid (80%, v/v).32 After stirring for 12 h, acetic acid was evaporated for 4 h using a rotary evaporator. The solution was washed with water to completely remove the acetic acid. The zein dough was then soaked under stirring (600 rpm) in hot (60°C) glycerol, a nonionic surfactant, for 15 min to interact with the hydrophilic amino acid residues of the unfolded zein. Next, the dough was left at room temperature (24±2°C) for 30 min and oven-dried at 60°C for 7 h. The dried dough was then ground for a few seconds and sieved through a 100-mesh sieve. Finally, a fine powder with a moisture content of 6.52% was obtained.\n\nThe next step involved an anionic surfactant, sodium dodecyl sulfate (SDS) solution (3%, w/v), which stabilized the zein proteins through electrostatic interactions between its negatively charged head with arginine, histidine, and lysine. In addition, its hydrophobic tail can interact with hydrophobic amino acids. These two types of surfactants were responsible for the stabilization of the emulsion in the next step. A modified zein solution (5%, w/w) was prepared using fine powder in an SDS solution (3%, w/v). The mixture was stirred at 1000 rpm and 90°C until a homogenous solution was obtained. A GA solution (20% w/w) was also prepared using GA powder in water. To prepare a modified zein-GA (MG) complex at a ratio of 1:1.5, a centrifuged (8250 rpm, 24°C, 10 min) GA solution was slowly added to the modified zein solution while gently stirring for 20 min at 24±2°C. The pH of the complexes was adjusted to 5. Based on our preliminary experiments, this ratio and pH condition were the most stable conditions for preparing FO emulsions.\n\nFirst, the freshly prepared MG complex was slowly added to glycerol (20%, v/v of the complex) under stirring (1000 rpm) at 60°C for 10 min. Subsequently, FO (5% v/v of the complex) was added dropwise to the mixture under the same stirring conditions. Homogenization (Homogenizer Ultra-Turrax T25 B S1, Malaysia) was carried out at 19000 rpm for 5 min. The emulsion was continuously processed using a bath sonicator (Yamato model 3510 BRANSON, USA) at 20°C for 20 min, and then adjusted to pH 5. A volume (25 mL) of the emulsion was poured into a polystyrene Petri dish (9 cm in diameter) and dried in a conventional oven at 40°C. A single-layer edible film containing FO (MGFO) was obtained after drying for 48 h.\n\nThe mixture in the upper layer was immediately poured onto the single/bottom layer to form a double-layer film. The mixture was prepared without FO. The freshly prepared complex, glycerol 20%, and GLE at addition levels of 1, 3, and 5% (w/v) were mixed and stirred at 1000 rpm for 10 min at 60°C. There was no homogenization, sonication, or pH adjustment after processing. Approximately 25 mL of the mixture was cast onto the bottom layer and dried for 48 h. The last stage was peeling the double-layer film off the petri dish, and the film was stored in a zip-lock bag at room temperature (24±2°C). The samples were labeled based on the addition level of GLE: MGFO-GLE 1%, MGFO-GLE 3%, and MGFO-GLE 5%.\n\nAnalysis of moisture content\n\nApproximately 1 g of double-layer edible film was weighed in the sample pan of a moisture analyzer (AND ML-50, Japan), and the moisture content was reported as % after drying at 105°C.\n\nThickness analysis\n\nThe thickness of the double-layer edible film was measured using a Digimatic Micrometer (Mitutoyo IP 65, Japan) at ten randomly selected spots.\n\nAnalysis of water vapor transmission rate\n\nVials, diameter and height respectively were 3 and 4.5 cm, were used for this measurement following the protocol of ASTM E96 with slight modifications.33 A weighed (5 g) amount of calcium chloride (RH 2%) was placed in a vial. A double-layer edible film (3 cm in diameter) was fitted to the top of the vial, and its position was maintained using parafilm. The weight of the vial containing calcium chloride and the film was then recorded, and the vial was kept in a desiccator containing a saturated solution of potassium chloride (RH 84%, at 25°C). The weight of the vial was recorded every 4 h for 3 weeks. The weight gain of the vial against time was plotted and the resulting slope was used to calculate the water vapor transmission rate (WVTR). The results were expressed as grams per square meter per day (g/m2/day).\n\nAnalysis of mechanical properties\n\nTensile strength and elongation at break (EAB) measurements were performed using a texture analyzer model EZ-SX (Shimadzu, Japan) based on the protocol of ASTM D882-02 with slight modifications.34 A double-layer edible film was prepared in rectangular strips at 1×7 cm and then handled by the grips. The measurement conditions were set to 50 mm, 25 mm/min, and 200 N for the initial grip separation, tensile speed, and load cell, respectively. The tensile strength was reported as kilopascals (kPa) and EAB as a percentage (%).\n\nThe surface morphology of the double-layer edible film was observed using scanning electron microscopy (SEM) (Miniscope TM4000Plus II Hitachi, Japan). Surface images from the top (100× and 1000× magnification) and bottom (1000× magnification) sides of the films were captured.\n\nDifferential scanning calorimetry (DSC) was performed using a DSC instrument (EXSTAR6000 model DSC6100 Hitachi, Japan) and thermogravimetric analysis (TGA) was performed using a TG/DTA instrument (EXSTAR6000 model TG/DTA 6200 Hitachi, Japan). Liquid nitrogen was supplied by a liquid nitrogen auto Supplier JSN-100DP-AS (Japan). The film (5.50-6.50 mg) was weighed in an aluminum pan using an analytical balance (Sartorius CP324S, Germany). After sealing, the pan containing the film and an empty pan (reference) were placed in the DSC or TG/DTA chamber. DSC analysis was performed in the temperature range of -30 to 270°C with the nitrogen flow rate and heating rate set at 50 mL/min and 10°C/min, respectively. The TGA was performed from room temperature to 270°C at a heating rate of 10°C/min.\n\nThis analysis was performed using a pour-plate method following the protocol of ISO 4833-1.35 A 0.1% peptone solution was prepared as a diluent. A suspension of sample (10−1) was prepared by adding 1 g of sample (single- or double-layered film) to 9 mL of diluent. The mixture was homogenized using a vortex, and serial dilutions were subsequently made from 10−1 to 10−3. From each dilution, 1 mL of the solution was transferred to a sterile disposable petri dish (diameter of 9 cm), followed by the addition of liquid TSA medium. The dishes were incubated for 48 h at 30°C.\n\nThe peroxide value (PV) was determined according to the method of Duan et al.17 with modifications. Single- and double-layered films (2.5 g) were weighed in sterile disposable centrifuge tubes, and 20 mL of an isooctane-isopropanol (3:1, v/v) mixture36 was added. The tubes were vigorously shaken and centrifuged at 8000 rpm for 10 min at 24°C. Filter paper (90 mm) was used to filter the homogenate. Approximately 0.5 g of the resulting solution was then mixed with 10 mL of isooctane-acetic acid (3:2, v/v) mixture. Approximately 200 μL of a saturated solution of potassium iodide was added to the mixture and gently shaken for 1 min. Subsequently, 80 mL of water was added, and the mixture was titrated with 0.01 N sodium thiosulfate. Automatic titration was performed using an automatic titrator (GT-200 Mitsubishi Chemical Analytech Co., Ltd., Japan).\n\nData were processed by one-way analysis of variance (ANOVA) using SPSS software (version 16.0). Duncan’s test with a significance level of P < 0.05 was performed to determine differences among the mean values of samples.\n\n\nResults and discussion\n\nThe extraction yield, bioactive compounds, antioxidant activity, and antibacterial activity of GLE are summarized in Table 1. Concentrating the GLE to 25 °Brix gave a yield of approximately 32%, and its pH was close to neutral because the extraction process utilized water solvent. The phenolic and flavonoid contents were obtained at approximately 15.81 mg GAE/g extract and 6.99 mg QE/g extract. These results were lower than the phenolic (24-58 mg GAE/g extract) and flavonoid (75-96 mg QE/g extract) contents of GLE observed in previous studies.37,38 The differences in the extraction method and conditions make water as a solvent, not the sole factor for this result. Non-conventional extraction techniques, such as microwave- and ultrasound-assisted extraction, have been used to effectively extract bioactive compounds from plant cells. For the conventional extraction method, the use of combination techniques for extraction, such as heating followed by stirring at room temperature for a long time (6 h), maceration and stirring, maceration and heating, and other combinatory models, can produce higher amounts of bioactive compounds. However, our simple conventional extraction method could satisfy the antioxidant activity of GLE, which was categorized as very strong.39 The IC50 (4.89 ppm) of ascorbic acid as a standard was about five times lower (greater antioxidant activity) than that of GLE (IC50 = 26.86 ppm). In addition, the GLE obtained in this study exhibited antibacterial activity against B. subtilis and E. coli in the inhibition range from weak to strong. The antioxidant and antibacterial activities of GLE were comparable to those of previous reports.40,41 Non-phenolic phytochemicals may also be responsible for these results; thus, a comprehensive phytochemical analysis of GLE should be performed in future studies. GLE 100% showed a more powerful inhibition against the tested bacteria; therefore, it was selected as the active compound for the upper/active layer of our double-layer films.\n\nTable 2 shows the significant impact of additional levels of GLE on the thickness and WVTR of the films (P < 0.05). The results indicated that a higher addition of GLE contributed to thicker films of approximately 50 μm thickness. The accumulation of higher GLE in the film matrix might have increased its solid content. However, an increase in film thickness had a detrimental effect on the WVTR of the film. The increase in the WVTR value can be attributed to the significant increase in the moisture content of the film (P < 0.05). Since the extraction process employed a water solvent, it is obvious that GLE is rich in hydrophilic compounds, thereby increasing the hydrophilicity of the film surface. Adding GLE 5% resulted in the highest thickness (971.67 μm) but barrier properties (WVTR = 17.04 g/m2/day) against moisture weakened. This result agreed with a previous study that reported that gelatin-based edible films containing GLE alone had the highest thickness but lower moisture resistance.42\n\nIn contrast, the addition of GLE did not significantly influence the mechanical properties of the double-layer films (P > 0.05), as shown in Table 2. By adding a lower level of GLE, the tensile strength of the film tended to increase, but the EAB constantly decreased. In this regard, there are fewer plasticizing effects of phenolic compounds of GLE and water in the MGFO-GLE 1%.43,44 The lowest addition level of GLE may result in a less hydrophilic film because the massive interaction of phenolic compounds and water molecules is minimized. Consequently, a higher strength (2.02 kPa) was required to break a thinner (872 μm) film. Instead, thicker films of MGFO-GLE 3% and MGFO-GLE 5% were less rigid and had higher extensibility. Nevertheless, the thickness of the double-layer film obtained in this study should be reduced by determining the suitable volume of the film-forming mixture for the bottom and upper layers.\n\nPhotographs of the double-layer films are shown in Figure 1. Darker films are shown in Figure 1B and 1C with GLE levels of 3 and 5%, respectively, while the addition level of GLE 1% produced a slightly lighter appearance (Figure 1A). Furthermore, the latter also presented a film with fewer cavities and troughs on its surface when magnified 100 times using SEM (Figure 2A). The incorporation of 3 and 5% GLE created more cavities and troughs, making the film surfaces more uneven (Figure 2B and 2C, respectively). This observation confirmed the WVTR results because the double-layer films incorporated with higher levels of GLE (3 and 5%) showed higher WVTR values for MGFO-GLE 3% and MGFO-GLE 5% (Table 2). A similar phenomenon was also observed in previous reports dealing with the incorporation of GLE,42 tea polyphenol,45 and seed extract of Syzygium cumini.46\n\nTop sides of films incorporated with GLE 1% (A), 3% (B), and 5% (C) (SEM images for 100× magnification). Top sides of films incorporated with GLE 1% (A1), 3% (B1), and 5% (C1) (SEM images for 1000× magnification). Bottom sides of films incorporated with GLE 1% (A2), 3% (B2), and 5% (C2) (SEM images for 1000× magnification).\n\nPerhaps the infiltration of FO droplets into the upper/active layer during the drying process of the film disturbed the integrity of the upper film-forming mixture, which was more hydrophilic. With respect to the ability of the MG complex to act as a wall material, such a lipophilic compound will be protected inside it. Hence, there is a dual function of the MG complex in the upper-layer matrix. On one hand, it functions to construct an interaction with GLE to form a compact base. It also works to stabilize FO on the other hand. This condition may lead to disparate complexation of chain packing in the matrix of the upper layer. As seen in Figure 2A1, 2B1, and 2C1, FO droplets were found on the top side of the double-layer film magnified 1000 times. It seems that the droplets were protected by a layer formed by the MG complex only or MG complex-GLE. Interestingly, the bottom layers of all double-layer films (1000 × magnification) possessed better uniformity, and neither holes nor troughs were observed (Figure 2A2, 2B2, and 2C2).\n\nDSC scans of double-layer films incorporated with 1, 3, and 5% GLE are illustrated in Figure 3A. For DSC analysis, Table 3 shows that MGFO-GLE 3% and MGFO-GLE 5% underwent glass transition at slightly higher temperatures, 53.46°C and 57.50°C, compared to that of MGFO-GLE 1% (T1/Tg = 52.74°C). The former films were also followed by the elevated melting temperatures (T2/Tm), 142.35°C and 139.18°C respectively for MGFO-GLE 3% and MGFO-GLE 5%, whereas Tm of MGFO-GLE 1% was 131.59°C. However, the enthalpy (∆H) among the samples did not show a certain trend, and the decomposition temperatures (T3) were identical.\n\nGLE 1% (silver thin line), GLE 3% (black bold line), and GLE 5% (gray bold line).\n\nOur result is in contrast to previous studies that reported that the decline in Tg and Tm of edible films was caused by the rising addition of plant extracts, generated from guava leaf,42 galangal,47 and pomegranate peel,48 to the film-forming solution. This can be attributed to the bioactive compounds of the extracts that promote the plasticization of the film by increasing its molecular mobility.49 This study contrarily observed that Tg and Tm were shifted to higher temperatures as the level of GLE increased, indicating that molecular mobility was limited. Protein (MG complex) and phenol (GLE) interactions via hydrophobic interaction, electrostatic interaction, and hydrogen bonding can be attributed to this phenomenon.50 This leads to the alteration of their original properties whilst creating more crosslinking so that a film with higher thermal stability can be made.51 In addition, zein, as a protein part of the MG complex, has a distinctive behavior, particularly its exceptional stretchability and rubbery.52 This enables the film to become preferentially extensible and less brittle without decreasing Tg and Tm. This was linked to the tensile strength and EAB of films with higher addition of GLE, MGFO-GLE 3%, and MGFO-GLE 5% (Table 2). This study displayed higher Tg and EAB than zein films impregnated with vegetable oils, 47-50°C Tg and 0.93-8.08% EAB.53 Moreover, this study produced a double-layer film that should be considered for comparison with other findings.\n\nThe TGA curves (Figure 3B) demonstrated the weight loss of the double-layer films during glass transition, melting, and degradation. Weight losses of MGFO-GLE 5% in the first step/WL1 (glass transition), as well as MGFO-GLE 3% and MGFO-GLE 5% in the second step/WL2 (melting) were noticeable. In the third step/WL3 (degradation at 260°C) and endpoint/WLep (267°C), the weight loss of MGFO-GLE 1% was noticeable (Table 3). The higher weight loss (WL1 and WL2) of MGFO-GLE 5% in the early stage could be associated with the greater moisture content (Table 2). The better retention of MGFO-GLE 5% during decomposition could be explained by the abundance of protein-phenol crosslinks and other types of intermolecular interactions. A previous study developed a zein-based edible film incorporated with essential oil/β-cyclodextrin and enriched with extracts of dill leaves.54 They pointed out several degradation steps of their edible films that involved the release of moisture, volatile compounds, and solvent at temperatures up to 150°C, dissociation of weakly bonded small functional groups from 150 to 270°C, and the removal of heat-stable compounds at temperatures higher than 270°C. Specifically, at 120-200°C, there is a degradation process of fatty acids.53 This process was recorded in the TGA curves of this study and showed a downward trend (Figure 3B). Furthermore, the WL3 (37.16%) and WLep (53.88%) of MGFO-GLE 5% were the lowest. Similar trends for the efficacies of the ethanolic extract of algae,55 ficus extract,56 and grape seed extract57 at higher concentrations to enhance the thermal stability of the edible films have supported the TGA results of this study. Above all, the DSC and TGA results suggested that GLE could be a driving force for the thermal stability of the double-layer film containing FO.\n\nAll edible films (single or double layer) possessed strong inhibitory activity against B. subtilis, but inhibition against E. coli was only found in double-layer films ranging from weak to moderate (Table 4). The antibacterial activity was significantly changed by adjusting the concentration of GLE (P < 0.05). This was in agreement with previous studies.42,58 The antibacterial activities of the edible films were dependent on the concentration of GLE in the film-forming solution. In this study, the film containing FO only (MGFO) exhibited strong inhibition (DIZ = 20.07 mm) against B. subtilis, but did not inhibit E. coli. The existence of the upper/active layer containing GLE contributed to (13-20 mm) to strengthen the antibacterial activity of the film against B. subtilis. The antibacterial activity (DIZ = 40.58 mm) of MGFO-GLE 5% was doubled. The incorporation of 5% GLE also markedly exerted the antibacterial activity of the film against E. coli (DIZ = 9.04 mm). Clearly, this result demonstrated that the double-layer edible film was more resistant to B. subtilis than E. coli. Previous studies have shown that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are more effective in inhibiting B. subtilis, Staphylococcus epidermidis, and Staphylococcus aureus than E. coli, Salmonella typhimurium, and Salmonella enteritidis.59,60\n\nSimplicity in the cell wall component of gram-positive bacteria enables the edible film material to easily penetrate the inner part of the bacteria. These fatty acids can concomitantly cause the rupture of bacterial cell membranes through disturbances in electron transport, enzyme production, and nutrient uptake, as well as the production of oxidation products.60 Bacterial cell walls can also be destroyed by the antimicrobial compounds inherent in GLE. Gram-positive bacteria can carry 30-70% peptidoglycan,61 allowing more hydroxyl groups of the phenolic compound to interact with the cell wall of B. subtilis.62 This leads to the destruction of the cell wall integrity and the interchangeability of the inner component of the bacteria with edible film materials. Therefore, the single- and double-layer films dramatically impaired B. subtilis. Unfortunately, owing to the complexity of the cell wall of gram-negative bacteria, the double-layer film could not optimally eliminate the growth of E. coli. Exogenous long-chain fatty acids can be used for the synthesis of lipopolysaccharides in E. coli to construct a formidable outer membrane. The fatty acids are transported into the inner membrane using FadL, an outer membrane protein.63 This confirmed that no antibacterial activity against E. coli was observed for the film containing FO only (MGFO). GLE was recognized for its role in improving the antibacterial activity of the double-layer film against E. coli, with a DIZ of GLE 100% was 12.55 mm (Table 1).\n\nAccording to the total plate count (TPC) in Figure 4, MGFO suppressed microbial viability until 3-day storage. MGFO-GLE 1% was found to restrain microbial viability for 5-day storage. Interestingly, microbial viability was remarkably suppressed after 15-day storage using MGFO-GLE 3% and MGFO-GLE 5%. Furthermore, the initial TPC (2 log CFU/g) of double-layer film containing higher GLE at levels of 3 and 5% was lower than the initial TPC (2.69 log CFU/g) of MGFO and TPC (2.23 log CFU/g) of MGFO-GLE 1%. Double-layer films had significantly lower TPC after 28-day storage, that is, 2.63, 2.55, and 2.32 log CFU/g for MGFO-GLE 1%, MGFO-GLE 3%, and MGFO-GLE 5%, respectively (P < 0.05). In contrast, MGFO showed higher TPC (3.04 log CFU/g) on the final day of storage. The present study found that the addition of GLE resulted in a better TPC reduction. It can also be inferred that the antibacterial activity of edible films (single- or double-layer) against B. subtilis and E. coli is a decisive factor in this regard.\n\nError bars show the standard deviation of the mean (n = 3).\n\nMonitoring PV is a common means to investigate the oxidative stability of edible films. In this study, the initial PV of the single-layer edible film containing FO only (MGFO) was approximately 10.46 meq peroxide/kg sample. This amount was significantly three- to five-fold greater than the initial PV of double-layer edible film incorporated with GLE, ranging from 2.56-3.83 meq peroxide/kg sample (P < 0.05). The upward trend of the PV of MGFO gradually rocketed after 3-day storage and another surge was identified after 15-day storage. From the initial point (day 0), there was an increase in the amount of PV up to 8.76, 11.04, and 15.44 meq peroxide/kg sample on days 15, 21, and 28 of storage, respectively. A steep climbing trend in the PV of the double-layer film was also found after 15-day storage. The PV of MGFO-GLE 1% rose to just over 9 meq peroxide/kg sample on day 28 of storage. PV of MGFO-GLE 3% and MGFO-GLE 5% increased at about 6.58 and 5.31 meq peroxide/kg sample respectively, on day 28 of storage. Our results were comparable to those of a previous study that employed rosemary and oregano essential oils to prevent oxidation of FO-containing edible films.17\n\nAlthough the upper layer of the double-layer film showed numerous cavities and troughs (Figures 2A, 2B, and 2C) and the possibility of water vapor permeation (Table 2), FO may have been stabilized by the MG complex alone or in interaction with GLE. Moreover, owing to the antioxidant activity of GLE (Table 1), it is not surprising that its incorporation into the upper/active layer considerably controlled the oxidative stability of the double-layer edible film. Donations of hydrogen atoms and/or single electrons to free radicals are possible mechanisms by which plant extracts slow down the rate of hydroperoxide formation.20–22 Based on the TPC (Figure 4) and PV (Figure 5) of double-layer films, it seems that the antibacterial and antioxidant activities of GLE were highly diminished after 15-day storage, indicating the soar trends in these results.\n\nError bars show the standard deviation of the mean (n = 3).\n\n\nConclusion\n\nThe present study revealed that the incorporation of GLE at all concentrations (1, 3, and 5%) demonstrated promising improvements in the antibacterial activity and oxidative stability of double-layer edible films containing FO. At additional levels of 3 and 5%, even though the thickness of the double-layer films increased, GLE reduced the moisture barrier ability as the moisture content increased. In addition, at the same levels, GLE rendered a rugged structure that was porous on the top side of the double-layer film under SEM observation. However, GLE at these levels advantageously improved the EAB of the double-layer films while decreasing the tensile strength without lowering Tg and Tm. Therefore, future work will address the drawbacks of this study by appropriately adjusting the ratio of the film-forming mixture for the bottom and upper layers. The current approach will contribute to the development of alternative techniques for FO enrichment of various solid food products.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nFigshare: Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film. https://doi.org/10.6084/m9.figshare.26076712. 64\n\nThe project contains the following underlying data:\n\n- Figures (photograph of double-layer edible film, micrograph of double-layer edible film, DSC and TGA curves of double-layer edible film, TPC of single- and double-layer edible films, PV of single- and double-layer edible films).\n\n- Raw data of GLE (total phenolic compound, total flavonoid compound, antioxidant activity, and diameter of inhibition zone) in Microsoft Excel Worksheet.\n\n- Raw data of edible films (moisture content, thickness, WVTR, mechanical properties, DSC, TGA, diameter of inhibition zone, TPC, and PV) in Microsoft Excel Worksheet.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nThe authors would like to thank the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and the Prefectural University of Hiroshima, Japan, for the research grant.\n\n\nReferences\n\nBrew BK, Toelle BG, Webb KL, et al.: Omega-3 Supplementation during the First 5 Years of Life and Later Academic Performance: A Randomised Controlled Trial. 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Publisher Full Text\n\nRojas-Lema S, Torres-Giner S, Quiles-Carrillo L, et al.: On the Use of Phenolic Compounds Present in Citrus Fruits and Grapes as Natural Antioxidants for Thermo-Compressed Bio-Based High-Density Polyethylene Films. Antioxidants. 2021; 10(1): 1–23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFu J, Alee M, Yang M, et al.: Synergizing Multi-Plasticizers for a Starch-Based Edible Film. Foods. 2022; 11(20). PubMed Abstract | Publisher Full Text | Free Full Text\n\nBiao Y, Yuxuan C, Qi T, et al.: Enhanced Performance and Functionality of Active Edible Films by Incorporating Tea Polyphenols into Thin Calcium Alginate Hydrogels. Food Hydrocoll. 2019; 97: 105197. Publisher Full Text\n\nAbdin M, El-Beltagy AE, El-sayed ME, et al.: Production and Characterization of Sodium Alginate/Gum Arabic Based Films Enriched with Syzygium Cumini Seeds Extracts for Food Application. J. Polym. Environ. 2022; 30(4): 1615–1626. Publisher Full Text\n\nGomaa MM, El Fadly E , Salama MA, et al.: Production of Bio-Composite Films from Gum Arabic and Galangal Extract to Prolong the Shelf Life of Agaricus Bisporus. J. Polym. Environ. 2022; 30(11): 4787–4799. Publisher Full Text\n\nKumar N, Pratibha, Trajkovska Petkoska A, et al.: Chitosan Edible Films Enhanced with Pomegranate Peel Extract: Study on Physical, Biological, Thermal, and Barrier Properties. Materials (Basel). 2021; 14(12): 1–18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTapia-Blácido D, Mauri AN, Menegalli FC, et al.: Contribution of the Starch, Protein, and Lipid Fractions to the Physical, Thermal, and Structural Properties of Amaranth (Amaranthus Caudatus) Flour Films. J. Food Sci. 2007; 72(5): E293–E300. PubMed Abstract | Publisher Full Text\n\nSun X, Sarteshnizi RA, Udenigwe CC: Recent Advances in Protein–Polyphenol Interactions Focusing on Structural Properties Related to Antioxidant Activities. Curr. Opin. Food Sci. 2022; 45: 100840. Publisher Full Text\n\nDu H, Liu C, Unsalan O, et al.: Development and Characterization of Fish Myofibrillar Protein/Chitosan/Rosemary Extract Composite Edible Films and the Improvement of Lipid Oxidation Stability during the Grass Carp Fillets Storage. Int. J. Biol. Macromol. 2021; 184(February): 463–475. PubMed Abstract | Publisher Full Text\n\nLiu L, Huang G, Li S, et al.: Replacement of Fat with Highland Barley β-Glucan in Zein-Based Cheese: Structural, Rheological, and Textual Properties. Food Chem. X. 2023; 20(2): 100907. PubMed Abstract | Publisher Full Text | Free Full Text\n\nde Almeida CB , Corradini E, Forato LA, et al.: Microstructure and Thermal and Functional Properties of Biodegradable Films Produced Using Zein. Polímeros. 2018; 28(1): 30–37. Publisher Full Text\n\nZolfaghari A, Bazargani-Gilani B, Aghajani N: Edible Film Based on Corn Zein Containing Dill Extract and Essential Oil/β-Cyclodextrin Inclusion Complex: Shelf Life Enhancement of Common Carp Fillet. Food Sci. Nutr. 2023; 11(7): 4275–4288. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMondal K, Bhattacharjee SK, Mudenur C, et al.: Development of Antioxidant-Rich Edible Active Films and Coatings Incorporated with de-Oiled Ethanolic Green Algae Extract: A Candidate for Prolonging the Shelf Life of Fresh Produce. RSC Adv. 2022; 12(21): 13295–13313. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBhatia S, Al-Harrasi A, Shah YA, et al.: Physicochemical Characterization and Antioxidant Properties of Chitosan and Sodium Alginate Based Films Incorporated with Ficus Extract. Polymers (Basel). 2023; 15(5). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMunir S, Hu Y, Liu Y, et al.: Enhanced Properties of Silver Carp Surimi-Based Edible Films Incorporated with Pomegranate Peel and Grape Seed Extracts under Acidic Condition. Food Packag. Shelf Life. 2019; (19, December 2018): 114–120. Publisher Full Text\n\nLuo Y, Liu H, Yang S, et al.: Sodium Alginate-Based Green Packaging Films Functionalized by Guava Leaf Extracts and Their Bioactivities. Materials (Basel). 2019; 12(18). PubMed Abstract | Publisher Full Text | Free Full Text\n\nShin SY, Bajpai VK, Kim HR, et al.: Antibacterial Activity of Eicosapentaenoic Acid (EPA) against Foodborne and Food Spoilage Microorganisms. Lwt. 2007; 40(9): 1515–1519. Publisher Full Text\n\nCoraça-Huber DC, Steixner S, Wurm A, et al.: Antibacterial and Anti-Biofilm Activity of Omega-3 Polyunsaturated Fatty Acids against Periprosthetic Joint Infections-Isolated Multi-Drug Resistant Strains. Biomedicines. 2021; 9(4): 1–15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMattarelli P, Sgorbati B: Chemotaxonomic Features in the Bifidobacteriaceae Family. Bifidobact. Relat. Org. Biol. Taxon. Appl. 2017; 99–114. Publisher Full Text\n\nLobiuc A, Pavăl NE, Mangalagiu II, et al.: Future Antimicrobials: Natural and Functionalized Phenolics. Molecules. 2023; 28(3). PubMed Abstract | Publisher Full Text | Free Full Text\n\nMay KL, Silhavy TJ: The Escherichia Coli Phospholipase PldA Regulates Outer Membrane Homeostasis via Lipid Signaling. MBio. 2018; 9(2): 1–13. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFigshare: Fish Oil-Containing Edible Films with Active Film Incorporated with Extract of Psidium Guajava Leaves: Preparation and Characterization of Double-Layered Edible Film. [Dataset]. Publisher Full Text"
}
|
[
{
"id": "317480",
"date": "10 Sep 2024",
"name": "Mohammed Sabbah",
"expertise": [
"Reviewer Expertise food edible packaging."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript entitled \"Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film\". Overall, this article presents a well-structured investigation into double-layered edible films containing fish oil and guava leaf extract. Here are some specific comments and suggestions:\nI suggest in the part of the Preparation of guava leaf extract to cite the reference of the method used. I recommend to see this paper Ref 1. I suggest citing the method that was used in the part of the analysis of the diameter of the inhibition zone. While the double-layered film concept is interesting, further discussion on the novelty compared to existing research on fish oil-containing edible films is needed. The rationale behind the specific concentrations used for fish oil (5%) and guava leaf extract (1, 3, and 5%) could be explained in more detail. Were these chosen based on preliminary experiments or existing literature? The conclusion could be strengthened by emphasizing the potential applications of these double-layered films in food packaging.\nRegards.\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": "12708",
"date": "30 Oct 2024",
"name": "Aji Sukoco",
"role": "Author Response",
"response": "Dear reviewer, We sincerely apologize for the delay in responding to your valuable comments on our paper. We are grateful for the opportunity to improve the quality of our paper entitled “Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film”. We have meticulously read the comments from the reviewer. We hope that the comments can be addressed by our additional explanations below. Thank you again for your great support by giving us constructive comments and suggestions. Sincerely yours, Authors: Aji Sukoco, Yukihiro Yamamoto*, Hiroyuki Harada, Atsushi Hashimoto, and Tomoyuki Yoshino Reviewer comments and author responses Comment 1: I suggest in the part of the Preparation of guava leaf extract to cite the reference of the method used. I recommend to see this paper Ref 1. Response to reviewer’s comment 1: Thank you for your valuable suggestion. We have added the reference (Sabbah et al., 2023) related to the preparation of GLE. Comment 2: I suggest citing the method that was used in the part of the analysis of the diameter of the inhibition zone. Response to reviewer’s comment 2: Thank you for your suggestion. We have added the reference (Mostafa et al., 2018) related to the analysis of the diameter of the inhibition zone. Comment 3: While the double-layered film concept is interesting, further discussion on the novelty compared to existing research on fish oil-containing edible films is needed. Response to reviewer’s comment 3: Thank you for your positive feedback and suggestions. To our knowledge, FO-containing edible film without or with antimicrobial/antioxidative agents is still rarely studied. This becomes a limitation in making a wide comparison with our results. However, it is noteworthy to note that our current result could tackle the main challenge of utilizing FO in edible film formulation, which is oxidation. It can be slowed down by the presence of a GLE-containing upper layer, as shown in Figure 5. We have made a comparison statement to the previous study of Duan et al. (2011) which can be found in the last sentence in the first paragraph of the “Peroxide value of edible films” section. Therefore, we believe that our study can be a piece of useful information for constructing a comprehensive discussion in the future. Comment 4: The rationale behind the specific concentrations used for fish oil (5%) and guava leaf extract (1, 3, and 5%) could be explained in more detail. Were these chosen based on preliminary experiments or existing literature? Response to reviewer’s comment 4: Thank you for the suggestions and comments. These concentrations were selected based on our unpublished reports. For the selection of FO concentration, 5, 10, and 15% of FO were incorporated into the edible film formulation. Improved characteristics in structural, thermal, and oxidative stability aspects of the edible film were properly achieved when using FO 5%. However, the initial point of peroxide value of the edible film was still relatively high up to 10 meq/kg, as shown in Figure 5. To deal with this, GLE at a concentration of 100% and at various additional levels (0.25, 0.5, 0.75, and 1%) in the film formulation was previously tested. Unfortunately, they did not show a significant reduction in peroxide value and also an improvement in antibacterial activity. So, we used a higher range of GLE levels up to 5% for further evaluation. We have added some explanations in our paper as suggested by the reviewer. Please find them in the first and second paragraphs of the “Preparation of double-layer edible film” section. In the first paragraph: FO 5% was chosen based on the preliminary test in our lab. It was revealed that at a concentration of 5%, FO properly improved the characteristics of the edible film in structural, thermal, and oxidative stability aspects, compared to those of FO 10 and 15% (unpublished report). In the second paragraph: GLE at an additional level of less than 1% did not significantly improve the oxidative stability and antibacterial activity of FO-containing edible film (unpublished report). Comment 5: The conclusion could be strengthened by emphasizing the potential applications of these double-layered films in food packaging. Response to reviewer’s comment 5: Thank you for the suggestion. We have added additional information in the last sentence in the paragraph of the conclusion section: The current approach will contribute to the development of alternative techniques for FO enrichment of various solid food products, such as ready-to-eat sausage, cheese, candy, and snack bars."
}
]
},
{
"id": "317481",
"date": "18 Sep 2024",
"name": "Nurul Saadah Said",
"expertise": [
"Reviewer Expertise Food packaging",
"film",
"pectin",
"gelatin"
],
"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\nAfter reviewing the manuscript entitled 'Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film', I found that this publication can be accepted for indexing after some major revisions. The comments are as follows:\nThe English needs to be checked, especially the grammar and word choice in the introduction and abstract sections. What is the significance of mixing zein, fish oil, and GLE as different layered film structures? On page 6, under characteristics of GLE, it was mentioned that 100% GLE showed a powerful antibacterial effect against tested bacteria, and it was selected as the compound for the upper layer film. However, in the film formulation, the GLE incorporated into the film was in the range of 1-5%. Please clarify this discrepancy. The WVTR analysis should discuss factors based on both sides of the film since it is double-layered. The functions of zein and fish oil should be discussed, especially zein, as it was mentioned in the introduction to impart hydrophobicity to the films. Please explain further why film extensibility (EAB) increases with higher GLE concentration. Please provide the trends results and references from previous studies as well. Please correlate the SEM structure with WVTR and mechanical properties results, as the uneven surface or open pores could be factors that impact the film properties. For the discussion on microbiological properties of films, how can you confirm that the antibacterial properties are solely attributed to GLE? In Table 1, GLE within 25-75% showed weak to moderate antibacterial activity. However, in the film, only 3-5% of GLE was incorporated and showed strong antibacterial activity, contradicting the findings in Table 1. Please clarify whether other factors such as zein or fish oil could be contributing to this significant effect. Please provide photos of the plate count for better understanding. In most discussions, only GLE was being discussed, while the functions of fish oil, gum, and zein were not highlighted in the abstract and conclusion. Please rewrite these sections, as other materials could contribute to the film properties.\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": "12709",
"date": "30 Oct 2024",
"name": "Aji Sukoco",
"role": "Author Response",
"response": "Dear reviewer, We sincerely apologize for the delay in responding to your valuable comments on our paper. We are grateful for the opportunity to improve the quality of our paper entitled “Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film”. We have meticulously read the comments from the reviewer. We hope that the comments can be addressed by our additional explanations below. Thank you again for your great support by giving us constructive comments and suggestions. Sincerely yours, Authors: Aji Sukoco, Yukihiro Yamamoto*, Hiroyuki Harada, Atsushi Hashimoto, and Tomoyuki Yoshino Reviewer comments and author responses Comment 1: The English needs to be checked, especially the grammar and word choice in the introduction and abstract sections. Response to reviewer’s comment 1: Thank you for your suggestion. Before being published, our paper was checked by an academic writing tool provided by F1000Research. We have revised the language and grammar of our paper accordingly. In the abstract section, we have changed the word “shelter” to “delivery system”. Comment 2: What is the significance of mixing zein, fish oil, and GLE as different layered film structures? Response to reviewer’s comment 2: Thank you for the comment. We have emphasized our sentences in the introduction section with respect to your concerns. We have elaborated it point-by-point, starting with the main challenge of FO for food uses which is associated with its oxidation rate (first paragraph). Next, the edible film is one of the alternatives to carrying FO without being involved in food processing. The use of single-layered edible film still poses a risk to the oxidative stability of FO, even if the antioxidative agent is incorporated. Therefore, a double-layered edible film is studied (second paragraph). After that, GLE is incorporated in an outer/upper layer with no FO to completely protect the FO-containing layer (bottom/lower layer). The advantage of GLE is also mentioned for both antioxidant and antimicrobial boosters (third paragraph). Following this, zein and GA are selected biopolymers to build a wall material for FO and GLE, as well as to construct a robust film matrix (fourth paragraph). Comment 3: On page 6, under characteristics of GLE, it was mentioned that 100% GLE showed a powerful antibacterial effect against tested bacteria, and it was selected as the compound for the upper layer film. However, in the film formulation, the GLE incorporated into the film was in the range of 1-5%. Please clarify this discrepancy. Response to reviewer’s comment 3: Thank you, we sincerely appreciate your deep review. Before being incorporated into the film formulation, the antibacterial activity of GLE was tested at concentrations of 25-100%. It was found that GLE 100% exhibited the strongest antibacterial effects against E. coli and B. subtilis. Next, this GLE 100% (with no dilution) was incorporated into film formulation at additional levels of 1, 3, and 5% (w/v of the complex). So, 100% is the concentration of GLE, while 1-5% is the additional level of GLE 100% in the film formulation. Comment 4: The WVTR analysis should discuss factors based on both sides of the film since it is double-layered. The functions of zein and fish oil should be discussed, especially zein, as it was mentioned in the introduction to impart hydrophobicity to the films. Response to reviewer’s comment 4: Thank you, we sincerely appreciate your deep review. In this paper, we focused on the characterization of double-layered edible film as affected by the different additional levels of GLE. MGFO (single-layer film containing FO) was only tested for the discussion in microbiological and peroxide value sections to prove the main function of GLE, as antioxidant and antimicrobial agents. We agree with your opinion, therefore, MGFO can be tested for further evaluation in future research projects to gain a comprehensive understanding of single- and double-layered edible films containing FO. We have added some explanations in the “Physical and mechanical properties of double-layer edible film” section: Additionally, the lower layer without GLE can be responsible for the reinforced water vapor barrier with respect to the hydrophobicity of zein and FO. Therefore, further characterizations of the physical properties of MGFO are needed to gain a comprehensive understanding of single- and double-layered edible films. Comment 5: Please explain further why film extensibility (EAB) increases with higher GLE concentration. Please provide the trends results and references from previous studies as well. Response to reviewer’s comment 5: Thank you for the comment and suggestion. We have emphasized our sentences in the second paragraph of the “Physical and mechanical properties of double-layer edible film” section with respect to your concerns. However, due to the limited existing studies about FO-containing edible film without or with antimicrobial/antioxidative agents, it is difficult to make a wide comparison with our results. We have added some explanations in this section: Instead, thicker films of MGFO-GLE 3% and MGFO-GLE 5% were less rigid and had higher extensibility due to stronger plasticizing effects and higher moisture content. The interaction between phenolic compounds and biopolymers may also have restricted the formation of intermolecular hydrogen bonds to exert a structural relaxation of the film. Previous findings found a lower EAB (less than 15%) with a higher tensile strength (less than 0.8 MPa) for FO-containing edible film enriched with rosemary and oregano essential oils. 17 The types of natural active substances and biopolymers can impart distinctive effects on the mechanical aspect of edible films due to chemical bonds and structural formation between them. Comment 6: Please correlate the SEM structure with WVTR and mechanical properties results, as the uneven surface or open pores could be factors that impact the film properties. Response to reviewer’s comment 6: Thank you for your interest in this issue. We have emphasized our sentences about the correlation between SEM structure and WVTR in the first paragraph of the “Morphology of double-layer edible film” section. We have also added some explanations in the first paragraph of this section: The porous surface directly permits water vapor transfer from the external or internal surroundings through the film matrix. Additionally, uneven surfaces with large cavities and troughs have made MGFO-GLE 3% and MGFO-GLE 5% less resistant (easy to break) to applying tensile strength. It was indicated by lower tensile strength values but higher EAB values, at once, confirming that they were inversely proportional relationships. Comment 7: For the discussion on microbiological properties of films, how can you confirm that the antibacterial properties are solely attributed to GLE? In Table 1, GLE within 25-75% showed weak to moderate antibacterial activity. However, in the film, only 3-5% of GLE was incorporated and showed strong antibacterial activity, contradicting the findings in Table 1. Please clarify whether other factors such as zein or fish oil could be contributing to this significant effect. Response to reviewer’s comment 7: We appreciate your deep evaluation of the microbiological aspect of edible film. We would like to confirm that: Table 1 shows the antibacterial activity of GLE 100% (without dilution) and GLE 25-75% (with dilution). Table 4 shows the antibacterial activity of edible film incorporated with GLE at a concentration of 100%, which was added into film formulation at additional levels of 1, 3, and 5%. We did not use GLE at concentrations of 25-75% in the preparation of edible film. For the analysis of the antibacterial activity of GLE 100%, it was shown that its effect was moderate against B. subtilis and strong against E. coli. When GLE 100% was incorporated into film formulation at all additional levels (1-5%), the film demonstrated a strong inhibition effect against B. subtilis. This was not only caused by GLE since MGFO (film without GLE) had a strong inhibition, which indicated that FO played an important role in this regard. The effectivity of the component in FO has been mentioned in the “Microbiological properties of edible films” section, such as in the last sentence in the first paragraph and the second sentence in the second paragraph. We have also revised the first paragraph in this section: The antibacterial activity was significantly changed by adjusting the additional level of GLE in the film formulation (P < 0.05). In previous studies, the antibacterial activities of the edible films were dependent on the concentration of GLE in the film-forming solution. 42 , 58 The antibacterial activity of the edible film against E. coli has been detailed in the second paragraph of this section. Comment 8: Please provide photos of the plate count for better understanding. Response to reviewer’s comment 8: Thank you for your suggestion. We have uploaded the photos related to TPC analysis to the data repository. However, we only have limited documentation since we did not anticipate making complete documentation for this analysis. Again, thank you for noting this and we hope the photo is sufficient to represent our activity in this analysis. Comment 9: In most discussions, only GLE was being discussed, while the functions of fish oil, gum, and zein were not highlighted in the abstract and conclusion. Please rewrite these sections, as other materials could contribute to the film properties. Response to reviewer’s comment 9: Thank you for your interest in this part. Referring to the purpose of this study: This study was undertaken to characterize FO-containing edible films that were double-layered with a film containing GLE, we thought that GLE was the key driving force in rendering the beneficial and detrimental effects on the characteristics of edible film because it was added at different additional levels. On the other hand, MG complex and FO were added at the same amount in the film formulation. We agree with your opinion, they still have a contribution to the film properties. We have added an explanation in the last sentence in the abstract section: MG complex and FO can also contribute to the performance of the edible film. We have added an explanation in the conclusion section: Other than GLE, the roles of MG complex and FO could have critical impacts on the surface integrity, thermal stability, antibacterial activity, and oxidative stability of the film."
}
]
},
{
"id": "314153",
"date": "21 Oct 2024",
"name": "Alfredo Vázquez-Ovando",
"expertise": [
"Reviewer Expertise Food science and technology",
"biotechnology"
],
"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 think the manuscript reports an interesting study, with a good methodological approach, relevant results and regularly well written. I note here some slight observations to the authors\nAn interesting question that arises from this approach is what happens if all the components (fish oil and guava leaf extract) are mixed in a single layer? If possible, that would be a good Control\nA brief information about the zein modification process should be included in the introduction\nThe microbiological characterization test against pathogens in the films should be included in the methods section; that is, include without too many details the size and pretreatment given to the film before being placed on the plates with the pathogen. Remove from where it is currently mentioned (analysis of diameter of inhibition zone).\nThe discussion mentions that the fish oil drops could have created cavities on the surface of the dried film. Was emulsification not performed during the manufacturing process? Is it possible that it is gas? Or where did the micelle go?\nHow long did it take from the film production to the initial peroxide index measurement? Explain why the film without guava leaf extract initially had a higher value than the others. Perhaps oxidation occurred during production.\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": "12710",
"date": "30 Oct 2024",
"name": "Aji Sukoco",
"role": "Author Response",
"response": "Dear reviewer, We sincerely apologize for the delay in responding to your valuable comments on our paper. We are grateful for the opportunity to improve the quality of our paper entitled “Fish oil-containing edible films with active film incorporated with extract of Psidium guajava leaves: preparation and characterization of double-layered edible film”. We have meticulously read the comments from the reviewer. We hope that the comments can be addressed by our additional explanations below. Thank you again for your great support by giving us constructive comments and suggestions. Sincerely yours, Authors: Aji Sukoco, Yukihiro Yamamoto*, Hiroyuki Harada, Atsushi Hashimoto, and Tomoyuki Yoshino Reviewer comments and author responses Comment 1: An interesting question that arises from this approach is what happens if all the components (fish oil and guava leaf extract) are mixed in a single layer? If possible, that would be a good Control. Response to reviewer’s comment 1: Thank you, it is an interesting question. Based on the findings of the high peroxide value of MGFO (single-layer film containing FO), we decided to use GLE in this study. We made the film with GLE in a double-layer structure as we thought that this concept could be better to completely protect the FO by considering the different characteristics of each layer, hydrophobic for the lower layer (containing FO) and more hydrophilic for the upper layer (containing GLE). As an edible film is usually placed on the foods in its actual application, which is highly in contact with the surroundings, the placement of FO-containing film in between the food matrix and GLE-containing film can be a good strategy to minimize the rapid oxidation of FO. In our study, the result of the peroxide values of MGFO and MGFO-GLE is shown in Figure 5. So, we guess that a single-layer film containing both FO and GLE may result in a high peroxide value because FO will be directly exposed to the environment. GLE and FO stand individually in the film matrix due to their different characteristics that cannot be easily managed by the MG complex. Comment 2: A brief information about the zein modification process should be included in the introduction. Response to reviewer’s comment 2: Thank you for your valuable suggestion. We have emphasized our sentences in the “Preparation of modified zein-gum arabic complex” section with respect to your concerns. We have added an explanation in the last paragraph of the introduction section: We used glycerol and sodium dodecyl sulfate (SDS) to prevent the aggregation of zein particles. Comment 3: The microbiological characterization test against pathogens in the films should be included in the methods section; that is, include without too many details the size and pretreatment given to the film before being placed on the plates with the pathogen. Remove from where it is currently mentioned (analysis of diameter of inhibition zone). Response to reviewer’s comment 3: Thank you for your suggestion. As per the instruction of F1000Research, the Methods sections should provide sufficient details of the materials and methods used so that the work can be repeated by others, we explained this section accordingly. Comment 4: The discussion mentions that the fish oil drops could have created cavities on the surface of the dried film. Was emulsification not performed during the manufacturing process? Is it possible that it is gas? Or where did the micelle go? Response to reviewer’s comment 4: Thank you for your deep review of this issue, it could enrich the information on our paper. Homogenization and sonication can sufficiently generate a fine emulsion, and this was only done for the lower layer formulation (containing FO). We did not perform such processes for the upper layer formulation (containing GLE) to prevent adverse effects on the chemical and/or structural properties of GLE. We agree with your opinion, so we have added an explanation in the second paragraph of the \"Morphology of double-layer edible film\" section: Disintegration of the film surface due to cavities and troughs can also be caused by the bubbles since the homogenization and sonication were not performed for the upper layer formulation. Comment 5: How long did it take from the film production to the initial peroxide index measurement? Explain why the film without guava leaf extract initially had a higher value than the others. Perhaps oxidation occurred during production. Response to reviewer’s comment 5: Thank you for your question. Measurement of the initial (day 0) peroxide value was done using freshly prepared films. We need approximately 60 min to cool down the temperature of the film before peeling. MGFO (single-layer film containing FO) was made after the 48-h drying process, while MGFO-GLE (double-layer) was made after the 96-h drying process. In the MGFO sample, FO can be rapidly oxidized during drying and cooling. However, FO oxidation of MGFO-GLE can still be retarded during the prolonged production time due to a layer containing GLE that has an antioxidative effect. We have emphasized our sentences in the second paragraph of the \"Peroxide value of edible films\" section with respect to your concerns: Moreover, owing to the antioxidant activity of GLE ( Table 1), it is not surprising that its incorporation into the upper/active layer considerably controlled the oxidative stability of the double-layer edible film, either during production or storage time. Donations of hydrogen atoms and/or single electrons to free radicals are possible mechanisms by which plant extracts slow down the rate of hydroperoxide formation."
}
]
}
] | 1
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https://f1000research.com/articles/13-816
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https://f1000research.com/articles/13-106/v1
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16 Feb 24
|
{
"type": "Study Protocol",
"title": "Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molar: a randomized, double-blind, controlled clinical trial.",
"authors": [
"Anuroop Singhai",
"Rajanikanth Kambala",
"Nitin Bhola",
"Rajanikanth Kambala",
"Nitin Bhola"
],
"abstract": "Introduction Surgical removal of an impacted third molar is one of the most common oral surgical procedures performed in dental offices. The postoperative phase is often associated with severe inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually prescribed to manage postoperative discomfort. NSAIDs have been associated with gastrointestinal bleeding, renal function disturbances, and platelet count reductions. Thus, the present study demonstrates the utility of aescin in managing postoperative discomfort after the surgical removal of impacted mandibular third molars. This study aimed to correlate salivary PGE2 levels and serum C-reactive protein levels with subjective and objective symptoms after surgical extraction of the mandibular third molar and their relationship with drug therapy.\n\nMethods The planned study is a single-center, double-blind, randomized, parallel, prospective clinical trial. Each patient will be prescribed either diclofenac sodium 150 mg/day or aescin (escin) 120 mg/day to be taken orally in divided doses for five days after surgically removing the impacted mandibular third molar. Pain will be assessed using a visual analog scale. Facial swelling and mouth opening will be recorded using a metric scale with standardized reference points. ELISA (enzyme-linked immunosorbent assay (ELISA) will be employed to measure salivary Prostaglandin E2 and serum C–reactive protein levels. All parameters will be recorded preoperatively (T0) on the second postoperative day (T1) and fifth postoperative day (T2).\n\nConclusion The proposed study is expected to show a favorable response to the administration of aescin for the management of postoperative discomfort compared to diclofenac sodium after third molar surgery. The proposed study is expected to positively manipulate the levels of salivary Prostaglandin E2 and serum C–reactive protein, which are reliable inflammatory markers. The outcome of this study may provide an efficacious and safe alternative to conventional nonsteroidal anti-inflammatory drugs for managing postoperative discomfort following third molar surgery.",
"keywords": [
"Aescin",
"Diclofenac",
"pain",
"swelling",
"C-reactive protein",
"prostaglandin E2",
"third molar"
],
"content": "Introduction\n\nThe backbone of most oral surgical practices worldwide is the extraction of impacted third molars. It is the most common oral surgical procedure1 performed in dental offics. However, the postoperative phase is often concomitant with severe pain, reduced mouth opening, and marked facial inflammation. Most patients are prescribed corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) to manage their postoperative discomfort. NSAIDS have been associated with gastrointestinal bleeding, disturbance in renal function, and a reduction in platelet count.2 Because of these limitations, many phytotherapeutic alternatives have been suggested. Aescin (Escin) has generated interest among researchers over the years. It is a practical part of Aesculus hippocastanum and was first isolated in 1953. It combines triterpene saponins and has demonstrated anti-inflammatory, antiedematous, and venotonic properties in various preparations.3 Thus, the present study demonstrates the utility of aescin in managing postoperative discomfort after the surgical removal of impacted mandibular third molars.\n\nAnother concern over the years has been the selection of NSAIDs, which predominantly depends on subjective factors, including the surgeon’s preference and personal experience. The need for an hour is to use a measurable marker of inflammation that can be quantitatively controlled by drug administration. Prostaglandin E2 (PGE2) is a reliable marker of inflammation, which has been isolated from various body fluids, including saliva.4 Owing to inflammation, C-reactive protein (CRP) emerges in the blood. Various studies have used CRP concentrations to monitor the healing process after drug therapy because of its sensitivity.5 This study aimed to correlate salivary PGE2 levels and serum C-reactive protein levels with subjective and objective symptoms after surgical extraction of the mandibular third molar and their relationship with drug therapy.\n\nDiclofenac was chosen for comparison because it has dose equivalence to aescin and is widely used to manage postoperative sequelae associated with third molar surgery.\n\n\nProtocol\n\nTo compare the efficacy of aescin (escin) and diclofenac in managing postoperative sequelae following surgical removal of impacted mandibular third molars and their effects on salivary Prostaglandin E2 and serum C-reactive protein levels.\n\n\nObjectives\n\nThe objectives of the present study are as follows:\n\n1. To compare the efficacy of aescin and diclofenac sodium in managing postoperative sequelae following surgical removal of impacted mandibular third molars.\n\n2. To compare the efficacy of aescin and diclofenac sodium in manipulating salivary Prostaglandin E2 (PGE2) and serum C-reactive protein (CRP) levels in patients undergoing surgical removal of the impacted mandibular third molar.\n\n3. To assess patient satisfaction regarding therapy.\n\n4. To evaluate the need for rescue analgesics in the postoperative period.\n\nA single-center, double-blind, randomized, parallel, prospective clinical trial will be conducted at the Sharad Pawar Dental College, Datta Meghe Institute of Higher Education and Research (DMIHER), Sawangi, Wardha.\n\nTwo groups will be created:\n\nGroup A – Diclofenac sodium\n\nGroup B – Aescin (escin)\n\nThe randomization process will be performed using a computer-generated subject allocation list.\n\nTrial participants and outcome assessors will be blinded.\n\nA total of 50 patients presenting to the outpatient department of oral and maxillofacial surgery, Sharad Pawar Dental College and Hospital, Sawangi, Wardha, India, with impacted mandibular third molars with a definitive indication for extraction will be enrolled in the study.\n\nInclusion criteria\n\n1. Patients giving informed written consent.\n\n2. Age group 18-40 yrs.\n\n3. ASA I and healthy ASA II physical status.\n\n4. Patients presenting with impacted mandibular third molars.\n\n5. Slightly or moderately difficult impacted mandibular third molars, according to the Pederson difficulty index.\n\nExclusion criteria\n\n1. Presence of comorbid conditions.\n\n2. Patients not reporting for follow-up as per study protocol.\n\n3. Presence of systemic infections.\n\n4. Presence of acute infection.\n\n5. Known allergies to drugs under study.\n\n\nMethods\n\nA clinical trial will be conducted with approval from the institutional ethics committee. The Consolidated Standards of Reporting Trials (CONSORT) statement guidelines will be used for this study.\n\nPatients will be prescribed either diclofenac sodium 150 mg/day or aescin (escin) 120 mg/day6 to be taken orally in divided doses for five days. Each patient will be subjected to one of the drugs after the procedure.\n\nSaliva collection will be done using a sterile polystyrene tube. A kit specific to PGE2 will be used to measure PGE2 levels in each specimen.4\n\nVenous blood will be subjected to a C-reactive protein (CRP) test to measure C-reactive protein7 levels in blood serum.\n\nSaliva and serum samples will be processed in Central Research Laboratory.\n\nAll patients will be administered 1 g of oral amoxicillin 1 h before the procedure. The standard surgical protocol for the removal of impacted mandibular third molars under local anesthesia will be followed.\n\nDrug therapy will be discontinued in cases of adverse reactions reported by the patient.\n\nPatients will be recalled on the second and fifth postoperative days. The number of tablets remaining will be calculated to assess compliance with the trial protocol.\n\nPatients will be required to adhere to the standard postoperative instructions following extraction.\n\nTramadol 50 mg will be prescribed as a rescue analgesic for the postoperative period.\n\n\nOutcomes\n\nPostoperative sequelae after surgical removal of the impacted mandibular third molar will be estimated by assessing pain, facial swelling, and mouth opening.\n\nPain: The visual analog scale (VAS)8 will be used to assess pain on a scale ranging from 0 to 10. The worst imaginable pain will be graded as 10, and the absence of pain will be graded as 0.\n\nFacial swelling will be measured using a metric tape and standard reference points.6 The following reference points will be used for the measurement:\n\n• Soft tissue pogonion - Tragus\n\n• The angle of the mandible - Corner of the eye\n\n• Corner of mouth - Tragus\n\nMouth opening: The maximum interincisal distance will be recorded using a metric scale with standardized ruler and a digital Vernier caliper.9\n\nSalivary Prostaglandin E2 and serum C-reactive protein levels will be measured by ELISA (enzyme-linked immunosorbent assay (ELISA) preoperatively (T0) on the second postoperative day (T1) and fifth postoperative day (T2).\n\nPatient satisfaction regarding therapy: Study subjects will classify their experience from 1 to 5, where 1 = poor, 2 = fair, 3 = good, 4 = very good, and 5 = excellent.\n\nThe need for rescue analgesics will be evaluated by counting the number of tramadol capsules or tablets required by the patient until the fifth postoperative day (T2).\n\nPain, facial swelling, mouth opening, serum C-reactive protein, and salivary prostaglandin E2 levels will be recorded preoperatively (T0) on the second postoperative day (T1) and fifth postoperative day (T2).\n\nPatient satisfaction regarding therapy and the need for rescue analgesics will be recorded on the fifth postoperative day.\n\nThe study will be a non-inferiority trial with a continuous outcome.\n\nThe sample size was established based on data obtained from a previous study conducted by Salgia et al.10 Serum C-reactive protein level was chosen as the primary outcome variable.\n\nFormula using mean difference\n\nα = Type I error at 5% at both sides two tailed\n\nZβ = 0.84 = Power at 80%\n\nPrimary Variable = CRP (C-reactive protein) levels\n\nThe mean difference after treatment CRP (mean ± SD) for the diclofenac group was 16.305 ± 3.977 (as per the reference article).9\n\nConsidering 20% clinically relevant margin for aescin = (16.305∗20)/100=3.26\n\nSample size:\n\nAssuming 10% dropout = 2\n\nTotal sample size required = 23 + 2 = 25 each group.\n\nThus, a total sample size of 50 subjects presenting with impacted mandibular third molars will be enrolled in the study.\n\nAll patients presenting to the outpatient unit of the Oral and Maxillofacial Department and fulfilling the enrolment criteria of the study will be recruited. The principal investigator coordinated with each patient to achieve the desired sample size.\n\n\nMethods: Assignment of interventions (for controlled trials)\n\nStudy participants will be randomized using the SCIENCER application. As a specific age range was chosen for the study, further stratification and subset creation will not be performed.\n\nAll the patients will be sequentially numbered for the purpose of allocation concealment.\n\nThe principal investigator will then enrol the participants. The research supervisor allocate the sequence and assign the participants to the intervention.\n\nTrial participants and the principal investigator will be blinded.\n\nUnblinding will be performed if a patient reports adverse side effects to the emergency unit during the follow-up period.\n\nDemographic, clinical, and laboratory data for each patient will be collected using the JOTFORM application.\n\nTelephonic reminders will be administered to each patient, according to the follow-up protocol. The research supervisor will directly dispense medication to the participants to promote retention.\n\nDemographic, clinical, and laboratory data will be segregated in the JOTFORM application based on patient codes. The filtered data will be downloaded and stored in an Excel spreadsheet for statistical analysis.\n\nStatistics: outcomes\n\nStatistics: additional analyses\n\nStatistics: analysis population and missing data\n\nPrimary variable\n\nInferential statistics will be used to compare the two groups for measurement scores, resulting in their mean change in a primary variable (visual analog scale, facial swelling, mouth opening, salivary prostaglandin E2, serum C-reactive protein) between baseline and end visits.\n\nBaseline variables will be tested for significance in the mean using ANOVA or Kruskal-Wallis test for more than two assessment periods. A post-hoc (Tukey’s or Duncan’s) test will be used to find a significant difference between the two groups for pair-wise comparison.\n\nOutcome variables\n\nOutcome variables will be tested for intra-difference in measurement at pre- and post-visits using a paired t-test to determine the mean’s significance. The unpaired t-test for comparison of two groups and ANOVA for comparison of three groups will be used for intergroup differences.\n\nStatistical analysis will be carried out using R-software free version.\n\n\nMethods: monitoring\n\nData monitoring will be carried out under the aegis of DSCC at DMIHER, Sawangi, and Wardha.\n\nThe interim analysis and review will be carried out by a member of the institutional ethics committee. Trial termination rights were reserved by the Institutional Ethical Committee.\n\nTelephonic conversations will be conducted prior to follow-up visits to inquire about any untoward events. In case of any adverse events, patients will be managed at the institutional hospital, and the necessary care will be rendered free of cost.\n\nAll adverse events will be reported to the Institutional Ethical Committee.\n\nAn interim audit of the trial will be conducted by the research supervisor. A final audit will be carried out by nominated members of the DSCC at the DMIHER, Sawangi, and Wardha.\n\nResearch ethics approval\n\nEthical approval has been obtained from the Institutional Review Board of the Datta Meghe Institute of Medical Sciences (now renamed as Datta Meghe Institute of Higher Education and Research) Sawangi, Wardha. (Reference number: DMIMS (DU)/IEC/2022/842 on 05/04/2022).\n\nAmendments to the protocol will be carried out only after approval from the Institutional Ethical Committee and DSCC at DMIHER, Sawangi, Wardha.\n\nThe Principal investigator will be required to answer any queries by the patient regarding the trial, and will be responsible for obtaining informed consent.\n\nNo biological specimen will be stored for ancillary studies and hence, ancillary study consent is not applicable.\n\nAccess to information from individual participants will be restricted to the principal investigator and research supervisor.\n\nThere are no financial or competing interests for the principal investigators for the overall trial or each study site.\n\nThe principal investigator and research supervisor will be custodian of the final trial data. The IEC and DSCC have access to the final trial dataset.\n\nThe trial will be conducted in accordance with good clinical practice and a strong adverse event-monitoring protocol. The safety of the procedures and drugs used in this study has been established. However, in case of any harm, compensation will be carried out according to institutional policy.\n\nThis clinical trial will be published as an original research article in an indexed journal. Open access release of the trial results will be performed to ensure optimum exposure of the scientific community.\n\nThe final trial data will be published as postdoctoral research (PHD thesis). The authorship associated with this trial will be limited to the principal investigator and research supervisor, with acknowledgements to individuals involved at various stages of the trial.\n\nThe PHD thesis will be made public after approval from DSCC.\n\nThe study is currently in the stage of a pilot project.\n\n\nDiscussion\n\nThere is growing interest in medical fraternity to find safer alternatives to NSAIDs. Despite advances in pharmaceutical technology, the pharmacokinetic properties of NSAIDs, such as diclofenac, have improved, however the dose-dependent gastrointestinal severe, renal, and cardiovascular adverse effects remain a cause of concern with the use of NSAIDs.\n\nPrevious studies have indicated that phytotherapeutic drugs have a favorable impact on inflammatory parameters and are safe for managing pain and discomfort following surgical removal of the third molar. Aescin (escin) is a phytotherapeutic drug that has been recognized for its anti-inflammatory properties. Previous studies have also suggested the glucocorticoid-like activity of aescin along with its gastroprotective action. However, further research is needed to examine the effectiveness of aescin in managing postoperative pain, facial swelling, and mouth opening following surgical removal of the third molar.\n\nNowak et al. (2021) conducted a study of 60 patients to assess the impact of A-PRF application during third molar surgery and its effect on C-reactive protein concentrations and wound healing. Patients who received A-PRF after the procedure had a faster rate of decreased CRP levels. They also suggested that A-PRF application significantly reduced the symptoms of regional inflammation and incidence of dry socket.5\n\nIn a detailed review of escin, Gallelli (2019) suggested that it has potent anti-inflammatory, antiedematous, venotonic, and endothelial protective properties. They described the basic mechanism of action of escin. Oral escin and its topical gel have been demonstrated to increase venous tone and reduce edema, resulting in quantifiable clinical progress in patients with blunt injury and chronic venous insufficiency.3\n\nIsola et al. (2018) conducted a clinical trial of eighty-two patients needing mandibular third molar extraction surgery. The study participants were randomly allocated into three groups. Group 1, placebo; Group 2, ibuprofen; Group 3, a phytotherapeutic drug (baicalin 190 mg, bromelain 50 mg, and escin 30 mg). All medications were prescribed twice daily for five days after tooth extraction. A visual analog scale was used to assess pain. A metric scale was used to record alterations in facial contours and mouth opening in millimeters. The outcome of this clinical trial implies that phytotherapeutic drug therapy effectively manages postoperative pain and discomfort.8\n\nGraziani et al. (2017) enrolled 40 patients in a case-control study demonstrating systemic inflammation following third molar removal. Patients who underwent third molar removal had more significant systemic inflammation, oxidative stress, and triglyceride levels than controls, and the first postoperative week had increased WBC counts and serum C-reactive protein and fibrinogen levels. The baseline values of the markers were observed three months after extraction. Higher systemic inflammation is associated with impacted third molars, and their elimination may signify a novel method for investigating acute inflammation and defining favorable systemic outcomes in humans.7\n\nMehra et al. (2013) conducted a double-blind, randomized clinical trial of 80 patients to assess the effect of four different pharmacological regimens on prostaglandin E2 (PGE2) levels in urine and saliva. Saliva and urine samples were collected at planned intervals. After removing the impacted lower third molars, the findings were compared with clinical progression. Patients who received ibuprofen fared significantly better in terms of most parameters. They further concluded that PGE2 is measurable in saliva and urine, and its rise and fall can be detected in both saliva and urine. They further suggested that PGE2 correlates with subjective and objective clinical symptomatology and that administration of anti-inflammatory drugs manipulates its levels in the body.4\n\nThe current scientific literature must be more extensive in demonstrating the correlation of the drug’s efficacy with reliable inflammation markers and associated clinical symptomatology.\n\nConsidering this, the present study will be a randomized, double-blind, non-inferiority trial to compare the efficacy of aescin and diclofenac sodium in the management of postoperative pain, swelling, and mouth opening, as well as their effects on salivary Prostaglandin E2 and serum C-reactive protein levels after surgical removal of the impacted mandibular third molar. The trial will be conducted as per SPIRIT guidelines.11\n\n\nTrial registration\n\nwww.ctri.nic.in\n\nTrial Registration Number is: CTRI/2023/09/058004\n\n\nTrial registration: data set\n\nNot applicable\n\n\nProtocol version\n\nv1 dated 26/07/2023\n\nIdentifier: Dr. Rajanikanth Kambala\n\n\nRoles and responsibilities: sponsor and funder\n\nStudy planning, data collection, research management, analysis, preparation of report and publication\n\n\nRoles and responsibilities: committees\n\nThe study will be carried out under the aegis of the Institutional Ethical Committee and the DSCC at DMIHER, Sawangi, Wardha, Maharashtra, India.",
"appendix": "Data availability\n\nNo data is associated with this article.\n\nZenodo: Extended data sheet for “Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molars: a randomized, double-blind, controlled clinical trial.”. Zenodo. https://doi.org/10.5281/zenodo.10605612. 11\n\nThis project contains the following extended data:\n\n• Model Consent form\n\n• Biological specimen\n\n• Patient Case Record form\n\nZenodo: SPIRIT checklist for “Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molars: a randomized, double-blind, controlled clinical trial.” https://doi.org/10.5281/zenodo.10605565. 12\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nBrkovic B, Andric M, Calasan D, et al.: Efficacy and safety of 1% ropivacaine for postoperative analgesia after lower third molar surgery: a prospective, randomized, double-blind clinical study. Clin. Oral Investig. 2017; 21: 779–785. PubMed Abstract | Publisher Full Text\n\nPiecuch JF: What strategies are helpful in the operative management of third molars? J. Oral Maxillofac. Surg. 2012; 70(9 Suppl 1): S25–S32. PubMed Abstract | Publisher Full Text\n\nGallelli L: Escin: a review of its anti-edematous, anti-inflammatory, and venotonic properties. Drug Des. Devel. Ther. 2019; 13: 3425–3437. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMehra P, Reebye U, Nadershah M, et al.: Efficacy of anti-inflammatory drugs in third molar surgery: a randomized clinical trial. Int. J. Oral Maxillofac. Surg. 2013; 42(7): 835–842. Publisher Full Text\n\nNowak JM, Surma S, Romańczyk M, et al.: Assessment of the Effect of A-PRF Application during the Surgical Extraction of Third Molars on Healing and the Concentration of C-Reactive Protein. Pharmaceutics. 2021; 13(9): 1471. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLandim FS, Filho JRL, Nascimento J, et al.: Effectiveness of nicotine patch for the control of pain, oedema, and trismus following third molar surgery: a randomized clinical trial. Int. J. Oral Maxillofac. Surg. 2020; 49(11): 1508–1517. PubMed Abstract | Publisher Full Text\n\nGraziani F, D’Aiuto F, Gennai S, et al.: Systemic Inflammation after Third Molar Removal: A Case-Control Study. J. Dent. Res. 2017; 96(13): 1505–1512. PubMed Abstract | Publisher Full Text\n\nIsola G, Matarese M, Ramaglia L, et al.: Efficacy of a drug composed of herbal extracts on postoperative discomfort after surgical removal of impacted mandibular third molar: a randomized, triple-blind, controlled clinical trial. Clin. Oral Investig. 2019; 23(5): 2443–2453. PubMed Abstract | Publisher Full Text\n\nAli AA, Belgasem KA: Maximum Mouth Opening among Libyan Population. J. Oral Health Dent. Sci. 2021; 5: 102–109.\n\nSalgia G, Kulkarni DG, Shetty L: C-reactive protein estimation: A quantitative analysis for three nonsteroidal anti-inflammatory drugs: A randomized control trial. Indian J. Dent. Res. 2015; 26: 43–47. PubMed Abstract | Publisher Full Text\n\nSinghai A: Extended data sheet for “Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molars: a randomized, double-blind, controlled clinical trial.”. Zenodo. 2024. Publisher Full Text\n\nSinghai A: SPIRIT checklist for “Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molar: a randomized, double-blind, controlled clinical trial.”. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "272570",
"date": "22 May 2024",
"name": "Gaetano Isola",
"expertise": [
"Reviewer Expertise Oral surgery",
"periodontitis"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIn the manuscript entitled: \" Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molar: a randomized, double-blind, controlled clinical trial\" the authors aimed to assess salivary PGE2 levels and serum Creactive protein levels with subjective and objective symptoms after surgical extraction of the mandibular third molar and their relationship with drug therapy. The proposed study is expected to show a favorable response to the administration of aescin for the management of postoperative discomfort compared to diclofenac sodium after third molar surgery. The proposed study is expected to positively manipulate the levels of salivary Prostaglandin E2 and serum C–reactive protein, which are reliable inflammatory markers.\nMajor comments: In general, the idea and innovation of this study regards the analysis of perioperative effects of third molar and biomarkers is interesting and novel because the role these aspects in medicine are validated but further studies on this topic could be an innovative issue in this field could be open a creative matter of debate in literature by adding new information. The study was well conducted by the authors; However, there are some concerns to revise that are described below. The introduction section resumes the existing knowledge regarding the important factor linked with the impact mediators involved together with biomarkers in dentistry. However, as the importance of the topic, the reviewer recommends to update the literature through read, discuss some recent interesting articles, that helps the authors to better introduce and discuss the role of CRP in periodontal treatment (similar to third molar) and on NSAIDs approaches (Isola G, et al., 2024 [Ref 1]) , (Isola G, et al., 2019 [Ref 2])\nThe authors should be better specified, at the end of the introduction section, the rationale of the study and the aim of the protocol. In the central section, should better clarify inclusions and exclusions criteria of the selected sample. Please better state the results obtained in the abstract. The discussion section appears well organized with the relevant paper that support the conclusions, even if the authors should better discuss the relationship regarding the periodontitis and risk of oxidative stress evolution and periodontal treatment that could improve the quality of life in oral diseases patients with impacted third molar. The conclusion should reinforce in light of the discussions. In conclusion, I am sure that the authors are fine clinicians who achieve very nice results with their adopted protocol.\nMinor Comments:\nAbstract:\nBetter formulate the abstract section by better describing the aim of the study\n\nIntroduction:\nPlease refer to major comments\n\nDiscussion\nPlease add a specific sentence that clarifies the results obtained in the first part of the discussion\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": [
{
"c_id": "11678",
"date": "21 Jun 2024",
"name": "Anuroop Singhai",
"role": "Author Response",
"response": "Dear Dr. Isola Thank you for taking the time to review our manuscript submitted to F1000research. We greatly appreciate your valuable feedback and constructive comments, which have undoubtedly enhanced the quality of our work. We have carefully considered each of your suggestions and have made the necessary revisions to address the concerns raised. Below, we outline the changes made in response to your comments: Introduction Section: We have provided a more comprehensive rationale for the study and explicitly stated the aim of the protocol at the end of the introduction section. This aims to offer readers a clear understanding of the objectives and purpose of our research. Methods Section: In the central section, we have meticulously clarified the inclusion and exclusion criteria of the selected sample. This ensures transparency and assists readers in understanding the criteria used for participant selection. Abstract: We have revised the abstract however as this is a study protocol in preliminary stage and data collection is still going on. So the results will be published after the completion of study. Discussion Section: We have reorganized the discussion section to further elucidate the relationship between periodontitis, periodontal therapy and inflammatory markers. Additionally, we have incorporated relevant literature to support our conclusions effectively. Conclusion: The conclusion has been strengthened to reinforce key insights gleaned from the discussion. By aligning the conclusion with the broader implications discussed, we aim to provide readers with a more robust and conclusive summary of our study approach and relevance. We are grateful for your acknowledgment of our clinical expertise and the positive assessment of our adopted protocol. Your encouraging words serve as motivation to continually strive for excellence in our research endeavors. Once again, we extend our sincere gratitude for your insightful review and invaluable input. We believe that the revisions made have significantly improved the manuscript and hope that it now meets the standards for publication in F1000research. Thank you for your continued support and consideration."
}
]
}
] | 1
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https://f1000research.com/articles/13-106
|
https://f1000research.com/articles/10-1295/v1
|
20 Dec 21
|
{
"type": "Research Article",
"title": "Healing through faith: meeting a chaplain coupled with biblical readings could produce lymphocyte changes that correlate with brain activity (HEALING study)",
"authors": [
"András Béres",
"Miklós Emri",
"Csaba Aranyi",
"Dániel Fajtai",
"Ferenc Nagy",
"Péter Szabó",
"Pál Bödecs",
"Edit Hörcsik",
"Éva Perpékné Papp",
"Ferenc Tomanek",
"Márta Kuti",
"Ágnes Petőfalviné",
"Hajnalka Kisdeákné",
"Gergely Bíró",
"Dániel Kovács",
"Bettina Bakos",
"Eszter Vinczen",
"Eszter Gál",
"Renáta Sillinger",
"Zoltán Szalai",
"Antal Szilágyi",
"Marianna Kiss-Merki",
"György Nagyéri",
"Judit Fodor",
"Tamás Németh",
"Erzsébet Papp",
"Imre Repa",
"Miklós Emri",
"Csaba Aranyi",
"Dániel Fajtai",
"Ferenc Nagy",
"Péter Szabó",
"Pál Bödecs",
"Edit Hörcsik",
"Éva Perpékné Papp",
"Ferenc Tomanek",
"Márta Kuti",
"Ágnes Petőfalviné",
"Hajnalka Kisdeákné",
"Gergely Bíró",
"Dániel Kovács",
"Bettina Bakos",
"Eszter Vinczen",
"Eszter Gál",
"Renáta Sillinger",
"Zoltán Szalai",
"Antal Szilágyi",
"Marianna Kiss-Merki",
"György Nagyéri",
"Judit Fodor",
"Tamás Németh",
"Erzsébet Papp",
"Imre Repa"
],
"abstract": "Introduction: Faith and systems of beliefs are known to impact not only the emotional, but also the immunological state of believers in ways that we are just starting to understand. Moreover, clinical implications of previous studies are limited. The aim of the “HEALING” (Hospital-based Ecumenical and Linguistic Immuno-NeuroloGic) Study was to examine immunological and neurological changes in hospitalized patients after meeting a chaplain coupled with biblical readings. Methods: Hospitalized patients were pre-screened to find those who were the most in need of an intervention. A passage from the Bible was read to them during a meeting with the chaplain at the bedside (n= 20) or in the chapel (n= 18). No meeting occurred in the randomized control group (n=19). Blood samples were taken 30 minutes prior, and 60 minutes after the meeting to measure white blood cells (WBC), interferon gamma (IFN-γ), immunoglobulin M (IgM), IgA, IgG, and complement 3 (C3). A subgroup of the visited patients was subjected to functional magnetic resonance imaging (fMRI), where they were played an audiotape of readings of the same passage from the Bible (n=21). Results: Lymphocyte counts increased more often after the more successful visits, but the immunological changes were not significant. Conversely, a significant (pfwe=0.003) correlation was revealed between changes in lymphocytes and activation of the angular gyrus (left BA39) during fMRI, a brain area involved in word recognition. Conclusions: Although limited by the sample size and cohort study design, the findings suggest the depth of psycho-immunological changes could depend on the degree to which the chaplains’ main message is understood.",
"keywords": [
"faith",
"hospitalization",
"psychoneuroimmunology",
"theology",
"fMRI"
],
"content": "Abbreviations\n\nBA: Brodmann area\n\nfMRI: functional magnetic resonance imaging\n\nNK cells: natural killer cells\n\nNSAID: nonsteroidal anti-inflammatory drug\n\nFor other abbreviations, see Table 1.\n\n\nIntroduction\n\nAfter Selye’s description on how stress modulates the immune system,1 a wide series of studies have shown direct and complex relation between acute,2-5 chronic stress, and the immune system,6-9 with evidence revealing the long-term effects of early-life stress on the immune response.10-12 Much less research has examined the modulating effect of positive emotions on immunity. Berk et al. found signs of immune stimulation among healthy adults after watching a humorous video.13 Later, Bennett et al. showed that the extent of immunological changes related to interventions intended to elicit positive emotions, may largely depend on the way these emotions are subjectively perceived: after showing a humorous videotape to healthy women, they did not find significant change in NK-cell activity as compared with the control group, only when they included the level of cheerfulness in their calculations; this was measured by counting the number of pre-established metacommunicative signals, from just smiling to laughing out loud, that indicate the amount of mirthful laughter elicited among the participants (“Humor Response Scale”).14 Studies traced down how positive experiences can trigger immunological changes in a chain reaction all the way down to the genetic code – creating” molecular signatures” related to mind-body interventions.15\n\nMost of the basic studies cited above were conducted with healthy adults, under non-clinical conditions, using non-personal tools (humorous videotapes), in the context of group sessions. The “SHoRT” study examined the immunological effect of positive emotions spurred by positive experiences of sick children being treated in a hospital.16 In the “HEALING” (Hospital-based Ecumenical and Linguistic Immuno-NeuroloGic) study presented below, the authors tried to elicit a positive emotional effect through a meeting with a chaplain in a pre-selected, adult population. Previous studies only examined the long-term effects of religious life on the immune system,17-19 or the relevant brain areas,20-22 while neurological events have been studied in isolation from other physical changes; moreover, the concept of religious practice occurring in a hospital setting is a sensitive issue, posing many practical difficulties (“God at the bedside”23). The “HEALING” study aimed to examine whether general psycho-neuro-immunological patterns could emerge from a single spiritual encounter within a clinical environment, or whether changes measured in previous studies were lost in the sea of other factors affecting the immune system.\n\nOur trial is registered at www.ClinicalTrials.gov (Identifier: NCT04112121, Registration date: 02/10/2019).\n\n\nMethods\n\nThe following randomized, parallel, open-labeled, controlled clinical trial study design was used:\n\n1. Effect of biblical readings on immunological parameters\n\n• Healing I. Measuring the effect of biblical readings at the bedside: At the center of the measurement was the first meeting with the chaplain, coupled with biblical readings by the patient’s bed. With this measurement, we tried to evaluate what immunological change the “acceptance of the Word” elicits. (In Christian religion, the listening of a passage from the Bible is considered to be a possible way of meeting God. Thus, in Christian terminology, the term “Word of God” refers either to a specific biblical passage, to the Bible in general or directly to the person of God24). The first blood sample was taken 30 minutes prior, the second blood sample was drawn after listening to the reading, 120 minutes after the first sample. Twenty patients were evaluated for this portion of the study.\n\n• Healing II. Measuring the effect of biblical readings at the hospital chapel: For this segment, as opposed to the previous measurement, the biblical reading took place in the hospital chapel, in small groups. Eighteen patients were evaluated in this portion of the study. The same biblical passage as the previous setting was used for the reading.\n\n2. Effect of biblical readings on functional magnetic resonance imaging (fMRI) activity\n\nThe patients from the previous two measurements were recruited for this measurement based on their mobility and the availability of the fMRI. During this portion of the study, the patients listened to biblical readings again; the same passage they first heard during one of the previous two measurements. The passage from the Bible was alternated with a control text, and a period of silence. We focused on whether any of the immunological or psychological parameters that appeared to change after the first listening showed any correlation with a change in fMRI activity.\n\nFor the graphic overview of the study design presented above, see Figure 1.\n\n“1.” and “2.”: blood samples.\n\nA total of 351 patients were screened for eligibility, 60 were randomized. Data from three patients were excluded from further analysis, because their medical condition required acute usage of oral NSAID/metamizole sodium. We analyzed results for a total of 20 patients in the bedside group (with an enrollment rate of up to two patients per week - Healing I), 18 patients in the chapel group (with an enrollment rate of three to five patients per week - Healing II), and 19 patients in the control group; we analyzed data from 57 patients in total. Of these, 22 patients were subjected to fMRI. We reported one technical failure to analyze fMRI data from one patient (the first patient in the chapel group), although the event was non-recurring. No other exclusion or loss of data occurred after randomization.\n\nMeasurements in the chapel (n = 18) occurred in five independent groups (minimum of three, maximum of five patients in each group). In three of the five groups (for 11 patients), we gave patients the option to receive communion: Catholic Eucharist, or Reformed Lord’s Supper. Of the 11 patients, five opted to receive Catholic Eucharist (four patients) or the Reformed Lord’s Supper (one patient).\n\nThe complete date range for participant recruitment was from 10 September 2015 to 2 January 2017; the nature of the interventions did not require follow up after 2 January 2017. There were no changes in trial outcome or methods after the trial commenced. The trial was stopped once the number of planned enrollments was met. We identified no harm or unintended effects on patients during or after the study.\n\nFor an overview of the enrollments, see HEALING study’s CONSORT Flow Diagram (cf. Figure 1 in the Extended data).\n\nThe complete protocol was approved by the Hungarian Medical Research Council’s Committee for Research Ethics (Appr.: 7245-1/2014/EKU (55./2014), authorization number: SOR/074/00130-4/2014), and our institutions’ Internal Ethical Boards (IG/02013-003/2015; 270/2015). Written informed consent was obtained from all participants. The research was conducted according to the principles expressed in the Declaration of Helsinki.\n\nInclusion criteria were: adult age (>18 years), being hospitalized, the ability for verbal communication, alertness, orientation, no sign of psychosis in their medical history, and willingness to participate in the study after written, informed consent. The hospital’s Infectious Diseases and Nephrology Wards were involved in the recruitment process. We proposed the enrollment for all patients satisfying the above criteria, except in case of any exclusion criteria. Mobility was also an inclusion criterium for the events taking place at the chapel and the fMRI measurements. Due to the chaplain’s limited time availability, not all eligible patients were able to participate in the study. The decision was based on the patient’s degree of need and willingness, as assessed by, and at the discretion of, the chaplain, using a quick stratification scoring system specifically designed to address the practical needs of this study (see Appendix 1, Extended data). Exclusion criteria were the inability to communicate verbally, psychotic state (as reported by the physician responsible for the patient), altered mental state, unwillingness to participate, active and treated malignant disease, steroid, oral non-steroidal anti-inflammatory drugs (NSAIDs) or metamizole- sodium use, since these could have influenced the measured immunological parameters.\n\nRandom assignment was based on the chaplain’s availability on the day of the measurement, rather than chance allocation of all the patients willing to be visited, so that the results of the control group were not biased by disappointments or frustrations caused by the cancellation/postponement of an anticipated visit. Thus, the atmosphere in the control group reflected the genuine psychological environment of a common day at the hospital, undisturbed by out-of-the ordinary events. The randomized control group consisted of patients who knew the goal of the measurement but were explicitly asked to help with their participating in the control group, i.e., they knew they weren’t going to meet the chaplain (by request, the encounter could be scheduled for a later occasion).\n\nEnrollment was arranged by the investigator. In order to minimize allocation bias, a covariate-adaptive, blocked, stratified randomization method was used: block size was fixed to 19 (±1) enrollments for each group, with a 1:1 allocation ratio. For the control group we enrolled patients whose diagnoses and number of days in the hospital was similar to the intervention groups, in order to ensure a good balance of participant characteristics, as the intervention groups were saturated.\n\nThe same passage was read in both groups (Isaiah 40, 27-31 – see Figure 2). Among the five groups in the chapel, communion was offered to three groups: Eucharist for Catholics, and Lord’s Supper for members of the Reformed church. We asked the patients and the chaplain to complete a questionnaire designed for the study (HEALING questionnaire, preliminary pilot testing, see Appendix 2, Extended data). In the groups at the chapel, we used the validated PSS-14 score.25 We took blood samples 30 minutes prior to, and 60 minutes after the encounter; due to some anticipated differences in the length of the visits, which were about 30 minutes each, it was the time interval between the two samples that was fixed to 120 minutes. We supplemented the lab measurements with microscopic examination of the blood smears26-28 (see Figures 4, 5, and 6), and measurements of IFNγ- (Healing I), or immunoglobulin M-, A-, G-, and C3- levels (enzyme linked immunosorbent assays), as well as some blood clotting factors (partial thromboplastin time [PTT] and international normalized ratio [INR]) (Healing II).\n\nIsaiah 40:27-31. New King James Version (NKJV).\n\nPatients heard readings by the chaplain and in their native language, Hungarian, in the study.\n\n“Innate (non specific) immune system” (extract). From: Szalka A, Timár L. Infektológia [Infectology]. Budapest: Medicina; 2005.\n\nPatients heard the text read by the chaplain in their native language, Hungarian, in the study.\n\nFor an overview of the measured psychological factors and immunological parameters, and the corresponding abbreviations, see Table 1.\n\n\n\n• Patient’s personal belief on how she/he got sick (BI1 and BI2)\n\n• Patient’s desire for the visit (BII1, BII4)\n\n• Patient’s satisfaction with her/his life (BI3, BI4, BI5, BI6)\n\n• Patient’s self-assessed burden caused by the hospitalization (BI7, BIV)\n\n• Patient’s personal belief on the way she/he will be healing (BII2, BII3)\n\n• Patient’s personal faith (BII1)\n\n• Patient’s religious practice (BIII2)\n\n\n\n• Patient’s/Chaplain’s overall satisfaction with the visit (AI and PI respectively)\n\n• Patient’s assessment on the intimacy of the encounter (AII)\n\n• Chaplain’s assessment on the patient’s openness (PII)\n\n• Patient’s assessment on the sincerity of the encounter (AIII)\n\n• Chaplain’s assessment on the extent she could connect to the patient (PIII)\n\n• Patient’s assessment on the trustworthiness of the chaplain (AIV)\n\n• Patient’s/Chaplain’s assessment on the emotionally turbulent, roiling effect of the encounter (AV, PIV)\n\n• Patient’s/Chaplain’s assessment on the emotional depth of the encounter (AVI, PV)\n\n\n\n• White blood cell count (WBC)\n\n• Neutrophils: change in\n\n✓ neutrophil count (dNeut)\n\n✓ percentage of neutrophils (dNeut%)\n\n• Eosinophils: change in\n\n✓ eosinophil count (dEo)\n\n✓ percentage of eosinophils (dEo%)\n\n• Basophils: change in\n\n✓ basophil count (dBas)\n\n✓ percentage of basophils (dBas%)\n\n• Monocytes: change in\n\n✓ monocyte count (dMono)\n\n✓ percentage of monocytes (dMono%)\n\n• Lymphocytes: change in\n\n✓ lymphocyte count (dLy-abs)\n\n✓ percentage of lymphocytes (dLy%)\n\n✓ percentage of large granulated lymphocytes (dLGL%)\n\n✓ percentage of small condensed lymphocytes (dSmallLy%)\n\n✓ percentage of activated lymphocytes (dMiddleLy%)\n\n• Lymphocyte/neutrophil ratio\n\n–change in: (dLy/Neut)\n\n• Platelet count (Plt)\n\n• Interferon-gamma level (IFNγ)\n\n• Immunoglobulin M level (IgM)\n\n• Immunoglobulin A level (IgA)\n\n• Immunoglobulin G level (IgG)\n\n• Complement C3 level (C3)\n\n• Partial thromboplastin time (PTT)\n\n• International normalized ratio (INR)\n\nIn the case of nominal values, non-parametric, associative-tests (i.e., Kolmogorov-Smirnoff) were used; in the case of immunological parameters, a normality testing followed by a parametric, paired-samples t-test was used. For all parameters measured in the study, we performed a network-analysis using two different methods: a Bayesian analyzer developed at UTE Budapest,29 and R package IsingFit [R code used: IsingFit (data, family = ‘binomial’, AND = TRUE, gamma = 0.1, plot = TRUE, progressbar = TRUE, lowerbound.lambda = NA, vsize = 10)],30 followed by a correlation analysis. The usually used p value of 0.05 was divided by the number of comparisons analyzed (Bonferroni correction).\n\nLater, an fMRI examination was carried out, which was contingent upon availability of the fMRI and the capability of the patients to be mobilized. After providing written informed consent, the patients enrolled in the fMRI examination were comforted to prevent any possible anxiety related to the measuring environment (narrowness and loudness often posing a challenge for patients), given instructions on the process, then laid down into the fMRI equipment, where they could hear the reading of the study on audiotape. Patients could stop the exam at any time by pressing a button.\n\nTo examine the regions of the brain that could be impacted by the current measurement, we performed fMRI measurements using a “block-design” technique in three functional states:\n\n1. In the active (“a”) block, patients could listen to the same passage from the Bible that they heard from their hospital bed or in the hospital’s chapel. They could hear the biblical passage once again read by the chaplain, in their native language (Hungarian) and in modern translation (Figure 2).\n\n2. In the control (“s”) block, the stimulus was a scientific text from audiotape, also read by the chaplain (Figure 3). Although this text was intelligible, it contained many difficult scientific words, and complex grammatical structures in Hungarian (a Finno-Ugric language), posing an intellectual challenge for patients.\n\n3. For a reference state, we introduced a block exposed to silence(“c”).\n\nThe MRI examinations were performed using a 1.5T Siemens Magnetom Avanto MR scanner (Syngo software versionVB17/A, Siemens Medical Solutions, Erlangen, Germany); for the timing of the stimulation and synchronization of data collection, Nordic Aktiva v1.1. equipment (Nordic Neurolab, Bergen, Norway) was used. For all patients enrolled, a structural 3D T1-weighted axial MP-RAGE recording (TE = 4.73 ms, TR = 1540 ms, TI = 800 ms, flip angle = 15°, slice-thickness 0.8 mm, 0.9 × 0.9 × 0.9 mm voxel-size) and a 3 sec. repetition time, 145 components’ blood oxygenation level dependent (BOLD) recording sequence (T2* gradient echo, TR = 3000ms, TE = 42 ms, flip angle = 90°, interleaved 4 mm axial slice thickness, 3.6 × 3.6-pixel size) was performed. During the fMRI measurements, the stimulation always started with a 15-second-long block of silence, followed by seven sections of activation blocks for 60 seconds each. The latter constituted of a 30-second-long active, and a 30-second-long control section or silence. During the measurements, the “block design” type stimulation was performed in a “c → as → ac → as → ac → as → ac → as” sequence order for all patients.\n\nIn the first phase of processing the fMRI image database, we assigned the T1-weighted structural images’ transformation into the MNI152 atlas-space using the FSL 5.0 and ANTS 1.9 programs31,32; using the segmentation algorithm of the FreeSurfer 5.0 software package33 in native space, we created the so-called brain-T1 pictures, only containing the images originating from the surface of the brain. With the help of the brain-T1 pictures, we transformed the motion-corrected fMRI picture sequences into the T1-picture corresponding to the person in question, and then with the defined atlas-space transformation we transformed it into the MNI152 atlas-space.31,32 Finally, on all fMRI image sequences, after eliminating the first four recordings containing the T1-effect, we applied an 8 mm isotropic Gaussian filtering. We used the SPM12 software34 to perform the statistical analysis on the created fMRI picture database at individual and population level. During the processing of the individual fMRI image sequences, using the a-c, a-s and s-c contrasts, we generated the statistical image databases (contrasting pictures) showing the differences between the effects of the various stimuli, which we used in the population-level analysis to statistically characterize the effect of the stimuli. Finally, we examined the differences in BOLD-answers linked to the active and control audio-stimuli, and their correlation with concrete clinical data corresponding to each patient. In the SPM analysis, in the comparison of the statistical differences between a-c, c-a, a-s, s-a, c-s and s-c activities, we sorted out the activation clusters containing a minimum of 100 voxels, with a Student-t = 3,58 threshold corresponding to the non-corrected p < 0.001 value from the SPM {T} pictures. We then used the MNI152 spatial coordinates of the cluster maximum, the maximal t-value, the corresponding FWE-corrected probability (peak-level inference), the size of the cluster and the FWE-corrected probability of the occurrence of the cluster (cluster-level inference) to characterize them.34\n\n\nResults\n\nThe enrollment period lasted one and a half years. We analyzed 57 patients in total. The median age of the patients was 64 (Healing I), 65 (Healing II), and 66 years old (control). The only criteria when enrolling patients for the control group was that the patient’s age, type of disease, and days of treatment did not show considerable difference compared with the intervention groups; due to the small number of patients willing to participate, statistical stratification needed to be used with constraints (cf. Table 1, Extended data).\n\nTo the question of whether they believe in God, the majority of patients (Healing I: 65%, Healing II: 77.8%) answered positively. Only 25%-38.9% of the patients responded that they actively practiced their faith. A total of 35% and 44.4% of the patients reported cathartic, or a very positive experience at the end of the measurement (maximal rating of 5/5 at Question “AI” in the HEALING “after” questionnaire, i.e., the patient’s overall satisfaction with the visit, as reported on a single item rating scale). 60% and 66.7% reported the visits to be deeply emotional (rating of minimum 4/5 at Question “AVI” in the HEALING “after” questionnaire, i.e., the patient’s assessment on the emotional depth of the encounter, as reported on a single item rating scale).\n\nAlthough changes in immunological parameters appeared to show tendentious deviations in both groups (bedside and chapel, see Figures 7 and 8), after Bonferroni correction, these changes were not statistically significant. Similarly, we did not find significant changes in immunological changes in the control group, therefore we reported no considerable difference between the intervention and control groups either (changes in IFNγ-levels were not considered to be clinically relevant, because the variance of the values at baseline was too elevated between the control and the intervention groups; we reported a miscalculation error retrospectively identified among PSS-14 scores – they were subsequently corrected in the raw data) (see Tables 2, 3, and 4, Extended data). With the statistical tools we used, we did not find significant correlation between the immunological and the psychological parameters (see Figures 9-10). It is an interesting observation that for the patients who were willing to take part of the communion offered, we measured decrease in lymphocyte counts without exception (see Figure 7).\n\nColumns show the number of patients. 1: lymphocyte count (Ly-abs) and percentage (Ly %) decreased; 2: Ly-abs and Ly % did not change in the same direction; 3: Ly-abs and Ly % increased.\n\n(A) Correlation analyses – Healing I; (B) Correlation analyzes – Healing II.\n\n(A) Analysis of correlations in Healing I with IsingFit. (B) Highlight of correlations in Healing I with a self-developed Bayesian analyzer (UTE Budapest). (C) Analyzis of correlations in Healing II with IsingFit. (D) Highlight of correlations in Healing II with a self-developed Bayesian analyzer (UTE Budapest). It appears the only - and weak - correlation between any psychological factor to any immunological parameter is the answer”b” to question”BI2” (i.e. answer “It is my fault that I became sick. I blame myself …” to the question on whether the patient feels responsible for his chronic illness (es)), correlating with neutrophile counts.\n\nFigures 9-10: Hungarian abbreviations were used. FVS: white blood cells. Lym: lymphocytes. Neut: neutrophils. Eos: eosinophils. Bas: basophils. Mono: monocytes. LymNeut: lymphocyte-neutrophil ratio. Gran_nagy: large granulated lymphocytes (LGL). Kozep: middle-sized lymphocytes. Kis_kond: small condensed lymphocytes. pc: percentage. Plt: thrombocytes. IFNg: interferon gamma. Ig: immunoglobulin. INR: International Normalized Ratio. aPTI: partial thromboplastin time. Fibr: fibrinogen. “elotte”: before, “utana”: after. UTE Budapest = Budapest University of Technology and Economics.\n\nWe obtained evaluable functional Magnetic Resonance Images (fMRIs) from a total of 21 patients in the second part of the study.\n\nThe comparison of the “biblical reading” block with the “silence” block showed significant (p < 0.001) activation in the right- and left BA 22 (Wernicke) and right- and left BA41 (Primary Auditory) areas solely. The comparison of the “control” block with the “silence” block showed significant (p < 0.001) activation in the same areas solely.\n\nAfter that, we performed several subgroup analyses to explore the correlations between the psychological factors or the immunological parameters, and the changes in fMRI activities between the “active” and the “control” blocks. We created the subgroups of patients according to the extent of the change that was measured in the psychological factors (chaplain’s overall satisfaction with the visit – “PI” – and patient’s overall satisfaction with the visit and on the emotional depth of the encounter – “AI”, “AVI” - as reported on the single item rating scales corresponding to the questions of the HEALING “after” questionnaire), or the immunological parameters (changes in the lymphocyte count [dLy-abs], percentage of lymphocytes [dLy%], and lymphocyte/neutrophil ratio [dLy/Neut], values as measured automated laboratory, changes in the percentage of large granulated lymphocytes [dLGL%] as measured with microscopic examination of blood smears). The subgroups contained approximatively similar (half-half) number of patients.\n\nIt was solely among the dLy-abs subgroups that there showed to be a tendency in regards to the change in fMRI activity. We found a weak difference between activity in the area of leftBA39 between the subgroup of patients who showed an increase in lymphocyte counts, versus the subgroup of patients who showed no relevant increase in lymphocyte counts (p = 0.393). No other psychologic or immunologic pair of subgroups showed any difference in regards of their change in fMRI activity.\n\nAfter that, we aimed to correlate the dLy parameters with the areas showing change in the fMRI activity. An invert linear correlation emerged (p = 0.019 with dLy%, p = 0.003 with dLy-abs) between the change in activity of the left BA39 area and the change in lymphocyte counts (see Figures 11-12). Finally, we performed the correlation analysis between the change in fMRI activity between the “active”- “control” periods, and the dNeut, dLy/Neut, AI, AVI, and PI factors or parameters, but we found no significant correlation.\n\nChange in lymphocyte count (“dLy”) versus difference between activation during the active “a” and the control “c” block (“response”) during fMRI at the leftBA39.\n\nChange in lymphocyte count (“dLy”) versus difference between activation during the active “a” and the control “c” block (“response”) during fMRI at the leftBA39.\n\nAccounting for both the correlation analyses and the subgroup analyses, altogether we examined only 12 factors or parameters, and therefore the level of significance was 0.05/12 = 0.00417. The correlation between the left BA39 area and change in lymphocyte count remained significant after the Bonferroni correction.\n\n\nDiscussion\n\nTaking Salopek’s “slow journalism” concept as a model [he makes a 21,000 mile-long journey (33.780 km) by foot, to retrace the pathways of our ancestors, the first humans who migrated from Africa and journeyed around the Earth - he posits that one must devote time to inter-personal connections in order to fully comprehend the human phenomenon - “Out of Eden Walk,”35], we consciously stood for the concept of “slow science” for a slow pace of methodology. The small sample size does not allow to extrapolate far-reaching conclusions; however, it is noteworthy that the sample size reaches or exceeds that of previous basic psycho-neuro-immunological and is standard in basic fMRI studies.20-22 Although patients were being treated for various illnesses while immersed in a clinical environment, the exact goal of the study was to know whether patterns marked enough to overwrite the heterogenicity of diagnoses could be elicited by the meetings. The diversity of the patients’ psychological and somatic conditions was managed by the encounter-centered study design, and the time interval between both data collections was relatively small (two hours), as compared to the length of the patient’s stay in the hospital (ranging from several days, up to weeks). The difference between the control and the intervention groups did not affect the main, significant result found with fMRI examinations, since that part of the study was performed within an auto-control setting.\n\nAlthough the measured immune changes were too small to be clearly distinguishable from other clinical effects, it is noteworthy that the results from the hospital bed show a striking similarity with those of the “ShoRT study”, where the children from whom blood samples were drawn in a non-painful way through branules, were visited by Smiling Hospital artists [SHoRT16]. It was once again the more successful visits that generated more marked changes in lymphocyte counts. However, the growing inconsistency in lymphocyte changes as patients got closer to the chapel, and especially the results of the group receiving communion, could refer to the sense of fascination and admiration mixed with tones of fear, as reflected by the psychological or religious term tremendum (see Rudolf Otto’s terminology of the “numinous” and “mysterium tremendum et fascinans” to describe the experience of the holy36). While the primary purpose of the intervention was to elicit positive emotions, the authors found that the same biblical reading could cause a wide range of thoughts and feelings, and different facets of the same emotional pattern could be amplified; this included fear of God, a recurrent motive of biblical encounters between God and man. For instance, in the Book of Exodus, God says to Moses: “I will make all my goodness pass before thee … Thou canst not see my face: for there shall no man see me, and live.” (Exodus 33, 19-20, KJV). More measurements are needed to clarify the statistical significance of these observations.\n\nFirst and foremost, it is worth noting that the most easily implementable technically, entailing the least possibility of error in the laboratory measurement, and automated lymphocyte count showed significant correlation with the fMRI results. This part of the study was not affected by the any unintended bias in the randomization process, since the fMRI part of the study was performed within an auto-control setting, for visited patients only. Yet, as Lieberman and Cunningham pointed out, whenever fMRI is used as a principal tool in a research setting, the number of measurements performed during each examination are so high that from a statistical point of view, even the use of the most conservative p values cannot rule out the possibility of type I errors, rendering the results of every fMRI study only meaningful following comparison with previous, and verification by subsequent studies, in case these also support the interpretations proposed.37 The current paper discusses a plausible interpretation of the findings while further research is needed to confirm the results.\n\nGiven that we could not rule out potential effects of magnetic resonance on immunological parameters from the fMRI examination, we intentionally separated fMRI measurements from immunological measurements. We laid out the “block-design” setting we used based on a meta-analysis of 48 studies,38 and works by Leff et al.,39 and Beaucousin et al.,40 who described different activation patterns on the fMRI of patients exposed to readings featuring different emotional content.\n\nThe fact that the comparison of the a-c and s-c periods resulted in a significant change in fMRI activity, whereas no difference was detected when comparing a and s, proves that the measurement was physiologically trustworthy: the patients heard the biblical readings, and control text likewise.\n\nThe biblical passage is an ancient, more than two and a half thousand years’ old text with plain words, and simple language structure, and is thought to have originally been intended to offer comfort. In contrast, the control text contained many difficult words for the layman, had long and difficult to follow sentences, and contained several words with potentially fear-inducing connotations. Thus, the result of the correlation analysis suggests the change in lymphocyte counts is related to the subjectively perceived content of the biblical reading as opposed to control text by the patients. The fact that the changes in lymphocyte counts were not significant, despite some widening in the confidence intervals, signaled that these changes were subject to limitations by the circumstances and by the disease; however, the correlation of these changes with the fMRI-s indicated that even when biblical readings did not appear to have a physiological effect, they could have an ordering, arranging effect, along some specific guiding principle, on a key parameter like the lymphocyte counts.\n\nAccording to neurosynth.org, previous scientific publications related to the region in the 2 mm area of the -52, -56, 26 cluster, have linked this area to the tactile and manual reconstruction of shape recognition, the learning of words, emotional speech, and the encoding of belief systems in neural pathways, and their linking with ethical decision making.41-47 It must be highlighted that the only brain area that showed a correlation with any of the immune parameters measured in this study - the left BA39, gyrus angularis - was contralaterally the same that is activated during meditation on/recitation of Buddhist scriptures.20 Although the depth of understanding could only mean cognitive understanding, due to the core nature of the phenomenon observed and the study design, it can also refer to broader spiritual experiences – which, in turn, can only partially be influenced consciously. Thus, the brain area involved in the correlation described above (gyrus angularis) could also be linked to the “Aha! moment”, which contains cognitive and emotional components alike but is not, or only partially, subject to conscious influence.\n\nThe authors would like to warn against interpreting the results of the study solely in terms of healing being accelerated by intimate religious experience. The spiritual, religious nature of the phenomenon observed obliges the integration of the theological viewpoint in the careful interpretation of the results. For centuries in the European tradition, theology – originally in close association with other areas of the basic scholar fileds \"septem artes liberales\" (seven liberal arts) - has been the delegated branch of academic studies as far as any aspect of the Bible was involved. More recently, modern research methodology has been embraced, especially by the reformed theologians of 20-21th centuries’ academic Christian theology, rendering it a branch of science only differing from other specialties by the principal focus of its observations being the “Word of God” instead of the natural world.24 This legitimizes the examination of how findings relate to the relevant theological literature in the discourse of a study involving religion, especially in the case of a study which used a biblical passage at its core.\n\nWhen one is examining the effect of the Word of God on man, trying to correlate it with any human parameter, dialectical theologians immediately emphasize the inherent asymmetry in the relationship between God and man. As Tillich submitted, we cannot control God with our will: “The experience of Spiritual presence does something that the human soul in itself cannot”48 Thus, the theologian points out that the immunological and neurological changes described in the measurement did not happened to the patient’s efforts, but without their knowing it. The content itself of the biblical message does not hold the promise of immediate physical healing. According to the Bible, Jesus’ healings give the impression that those had a signal value. Jesus did not heal everybody (cf. the account of the healing at Lake Bethesda, Jn 5, 1-9), and in a critical moment he himself accepted his own death. There are instances when Jesus’ Gospel has been theorized to give strength not just to overcome the disease, but to endure it. Nevertheless, correlation also exists in theology. Tillich wrote: “The answers emerging from the event of revelation are comprehensible only if they are in correlation with the questions of our whole existence, the existential question.”48 Tillich used the method of correlation mainly in respect of the dialogue between the Christian message and the contemporary society (culture). The present paper describes how the method of correlation can also be used in the dialogue between natural sciences, social sciences and theology. Indeed, in Christian religion, the encounter between God and man can take place within a human relation, or also during a biblical reading, i.e., listening to the “Word of God”.24 In this context, the meeting with the chaplain could trigger the recollection of some genuine, primordial experience of meeting with the transcendent, a phenomenon that could be the expression of ancient, maybe even pre-Christian patterns buried in our collective subconscious, and bringing up ancient, genuine, instinctive reactions, according to Jung’s concept on the working mechanism of “archetypes”, i.e., of inherited inner patterns buried in the collective subconscious.49 The simultaneous change of the nervous and immune systems that was recorded in the present study during repeatedly listening to the Bible, confirms the possibility that in addition of the psychological effects, general biological patterns could also be activated during the meeting of God and man. In line with this concept, beyond the personal healing stories, the Bible’s synoptic contain numerous accounts of mass healings – i.e., Mt 4,24.8,16.12,15.14,14.15,30.19,2.21,14; Mk 6,56; Lk 4,40.9,11 – giving the impression that the meeting with Jesus also brought about general healing effects in people.\n\nThe contradiction presented above – namely, that the Word of God would be healing, whilst the main message of the Word sometimes does not bear healing, but cross – is solved if we put the question and the results of our study in the context of modern theologians’ evolutionary theory, which states that religiousness and life of faith also have developmental aspects, therefore can be understood as having an evolutionary dimension, with a direction of growth, at times including the notion of suffering through the process (see Whitehead50 and “process theology”), and thus cannot be considered as opposed to the natural sciences’ concept of evolution.\n\nAccording to Pannenberg, “at the end of the 19th century in the first half of the 20th, sadly, Christian churches and theologians could not recognize that the teaching of evolution gives an unprecedented possibility for theology in regards of the possibility of its relationship with modern science. The fight against Darwinism was one of the mistakes resulting in the most serious consequences during the history of the relation of theology with sciences.”51 The findings of the current study can be a small contribution to support this position, and put a novel lighting on the fact that, despite the lack of significant and noticeable biological effects, some form of religious belief could so indefatigably spread over and survive in the whole human species up until that day. If indeed, depending on the depth of spiritual understanding, the religious experience could influence the lymphocyte count, then it could contribute to prevent or recover from the diseases, hence provide an evolutionary advantage in the sense the natural sciences use this term. On the other hand, from the theologian’s perspective, the goal of evolution is not the survival and accommodation in the narrow sense of the word. Teilhard de Chardin wrote: “as early as in St. Paul and St. John we read that to create, to fulfill and to purify the world is, for God, to unify it by uniting it organically with himself”, and God is “from this point of vantage in the heart of matter, assuming the control and leadership of what we now call evolution.”52 He states that “through human socialization, whose specific effect is to involute upon itself the whole bundle of reflexive scales and fibers of the earth, it is the very axis of the cosmic vortex of interiorization which is pursuing its course.”52 Pannenberg often alluded to Gods’ appearance in world history, in the person of Jesus, as an event that can be considered the portent, the anticipation of the future.53 In this sense, healings are of signal value because they hint a precursory picture of a harmonious God-man relationship, including all its psychical and physical aspects – as Pannenberg wrote: if, “(like Teilhard de Chardin), we can consider life’s evolution as the process of the creation of life forms of increasing complexity and at the same time becoming increasingly introspective, then we can also state, that in the succession of different forms of life by the creatures, is expressed the increase in the shareholding of the divine Spirit, of life’s Spirit.”51,52\n\nFaith is an evolutionary advantage, in the theological sense because the goal of evolution is the increase in the shareholding of the divine Spirit.52 This is the end towards which the result of our measurement converges.\n\n\nData availability\n\nFigshare: Healing Study Beres et al. - Part 1: Psychological and Immunological Changes after meeting a Chaplain coupled with Biblical Readings among Hospitalized Patients, https://doi.org/10.6084/m9.figshare.16750384.v154\n\nFigshare: Healing Study Beres et al. - Part 2: fMRI Changes after meeting a Chaplain coupled with Biblical Readings and Recalling the Visits with Audiotapes among Hospitalized Patients, https://doi.org/10.6084/m9.figshare.16751851.v155\n\nFigshare: HEALING Study Beres et al. - F1000Research - extended data, https://doi.org/10.6084/m9.figshare.17029715.v156\n\nFigshare: CONSORT checklist for “Healing through faith: meeting a chaplain coupled with biblical readings could produce lymphocyte changes that correlate with brain activity (HEALING study)”, https://doi.org/10.6084/m9.figshare.17029715.v156\n\nData are available under the terms of the “figshare” repository (licence CC BY 4.0).\n\nData generated from the above raw data are included in this article.",
"appendix": "Acknowledgements\n\nWe thank all patients who participated in this study for their engagement.\n\nWe thank András Falus MD, PhD, DSc, for his inestimable help in making this study possible.\n\nWe thank Péter Antal, PhD and Bence Bruncsics for their invaluable help in the statistical analysis of Part 1 (Psycho-immunological changes measured after the experience of the meeting) of this study.\n\nWe thank Tamás Szelestei, MD, PhD, and Josef Fuisz, ThD, their suggestions were instrumental for the final version of this article.\n\nFor English consultation, we would like to express our profound gratitude to Tricia Garrison, creative collaborator on the “Happiness Helps Healing” initiative.\n\nWe thank Andrea Varga, MPharm, mother of Dr. Béres, for having taken the risk to substantially sponsor the study.\n\nWith this study, the Kaposi Mór Teaching Hospital pays tribute to the 500th anniversary of the Reformation.\n\n\nReferences\n\nSelye J: Életünk és a stress. 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PubMed Abstract | Publisher Full Text\n\nBuhle JT, Silvers JA, Wager TD, et al.: Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cereb. Cortex. 2013 Jun 13; 24: 2981–2990. Publisher Full Text\n\nLeff AP, Iverson P, Schofield TM, et al.: Vowel-specific mismatch responses in the anterior superior temporal gyrus: an fMRI study. Cortex. 2009 Apr; 45(4): 517–526. Epub 2008 Feb 7. PubMed Abstract | Publisher Full Text\n\nBeaucousin V, Lacheret A, Turbelin MR, et al.: FMRI study of emotional speech comprehension. Cereb. Cortex. 2007 Feb; 17(2): 339–352. Epub 2006 Mar 8. PubMed Abstract | Publisher Full Text\n\nYarkoni T: Studies reporting activation within 2 mm of (-52, -56, 26). Neurosynth. Reference Source\n\nJäncke L, Kleinschmidt A, Mirzazade S, et al.: The role of the inferior parietal cortex in linking the tactile perception and manual construction of object shapes. Cereb. Cortex. 2001 Feb; 11(2): 114–121. Publisher Full Text\n\nWoodruff CC, Johnson JD, Uncapher MR, et al.: Content-specificity of the neural correlates of recollection. Neuropsychologia. 2005; 43(7): 1022–1032. Epub 2005 Jan 24. PubMed Abstract | Publisher Full Text\n\nYoung L, Saxe R: The neural basis of belief encoding and integration in moral judgment. NeuroImage. 2008 May 1; 40(4): 1912–1920. Epub 2008 Feb 14. PubMed Abstract | Publisher Full Text\n\nCooper EA, Hasson U, Small SL: Interpretation-mediated changes in neural activity during language comprehension. NeuroImage. 2011 Apr 1; 55(3): 1314–1323.Epub 2011 Jan 11. PubMed Abstract | Publisher Full Text\n\nDrolet M, Schubotz RI, Fischer J: Explicit authenticity and stimulus features interact to modulate BOLD response induced by emotional speech. Cogn. Affect. Behav. Neurosci. 2013 Jun; 13(2): 318–329. PubMed Abstract | Publisher Full Text\n\nFerreira RA, Göbel SM, Hymers M, et al.: The neural correlates of semantic richness: evidence from an fMRI study of word learning. Brain Lang. 2015 Apr; 143: 69–80. Epub 2015 Mar 19. PubMed Abstract | Publisher Full Text\n\nTillich P: Rendszeres teológia [Systematic Theology]. István S, translator. Budapest: Osiris; 2003.\n\nJung CG: The Archetypes and the Collective Unconscious. Princeton: Princeton University Press; 1959.\n\nWhitehead AN: Process and Reality. New York: The Free Press; 1978; pp. 347–348. 351.\n\nPannenberg W: Rendszeres teológia II. kötet [Systematic Theology, Volume 2]. Görföl T, translator. Budapest: Osiris; 2006; pp. 39. 99.\n\nde Chardin PT : The Phenomenon of Man. New York: Harper Perennial Modern Thought; 2008; pp. 293–294. 302, 306.\n\nPannenberg W: Systematic Theology. Michigan: Wm. B. Eerdmans Publishing Co.; 1997; Volume 3. : p. 335. (Chapter 13, III., § 2., “The Lord’s Supper and Christian Worship”)\n\nBéres A, Szabó P, Petőfalviné Á, et al.: Healing Study Beres et al. - Part 1: Psychological and Immunological Changes after meeting a Chaplain coupled with Biblical Readings among Hospitalized Patients. figshare. Dataset. 2021. Publisher Full Text\n\nBéres A, Emri M, Aranyi C, et al.: Healing Study Beres et al. - Part 2: fMRI Changes after meeting a Chaplain coupled with Biblical Readings and Recalling the Visits with Audiotapes among Hospitalized Patients. figshare. Dataset. 2021. Publisher Full Text\n\nBéres A, Emri M, Aranyi C, et al.: HEALING Study Beres et al - F1000Research - extended data. figshare. Dataset. 2021. Publisher Full Text"
}
|
[
{
"id": "120035",
"date": "21 Feb 2022",
"name": "Andrew B. Newberg",
"expertise": [
"Reviewer Expertise Neuroimaging",
"meditation"
],
"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\nRegarding the article entitled, “Healing through faith: meeting a chaplain coupled with biblical readings could produce lymphocyte changes that correlate with brain activity (HEALING study)”, overall, this study is potentially quite interesting and would be of interest. However, the lack of positive results and the confusing presentation with heavy reliance on religious and theological discussion substantially limits the value of this article from a scientific perspective.\nIntroduction The introduction needs to clearly state what the authors’ hypotheses were. Without this, it is difficult to understand what they are trying to accomplish in their study. Do they think that lymphocyte counts will increase or decrease? What correlations are they expecting? What parts of the brain are they anticipating will be involved. They should consider elaborating on studies of mindfulness and other meditation practices on immune function.\nMethods The authors should clarify how subjects were allocated since they were not truly randomized, but allocated by convenience. The authors state: The decision was based on the patient’s degree of need and willingness, as assessed by, and at the discretion of, the chaplain… What does this sentence mean? Is the chaplain deciding who is included in the study? This seems highly problematic.\nThe authors state: The randomized control group consisted of patients who knew the goal of the measurement but were explicitly asked to help with their participating in the control group, i.e., they knew they weren’t going to meet the chaplain (by request, the encounter could be scheduled for a later occasion). Does this mean that they knew they were controls or just that they weren’t meeting with the chaplain?\nThe authors state blood collections occurred 30 minutes prior to and 60 minutes after the spiritual intervention. Can they provide an explanation as to why this particular timing? Is this based upon any data regarding the speed with which these serum markers can change?\nRegarding the passages read to the subjects, is it possible that the Isiah chapter is something that the participants know well? Would it have been better to have read from some other passage of the bible such as a listing of names which has a potential neutral effect rather than something that is medically oriented?\nPart I Results This comes across as a very confusing section. The tables and figures are very confusing and in the end, it seems that no results were significant. Perhaps this section can be substantially altered to state that there were no significant findings. If there was a trend towards significance in any of the values, perhaps the authors can use this information to provide an effect size that might be useful for developing future studies. But otherwise, it does not seem appropriate to include tables and complex figures on data that is non-significant.\nPart II Results:\nPerhaps this was not clear, but were there differences between the active prayer block and the control block or just between prayer and silence? This might be particularly relevant and interesting in that hearing a religious recitation affects the brain differently than a neutral/scientific recitation. This might also be more relevant in terms of other physiological and psychospiritual measures. Otherwise, as with the section above, the authors should really only show the significant results and can delete Figure 11.\nIn the text, the authors state: After that, we aimed to correlate the dLy parameters with the areas showing change in the fMRI activity. An invert linear correlation emerged (p = 0.019 with dLy%, p = 0.003 with dLy-abs) between the change in activity of the left BA39 area and the change in lymphocyte counts Can they clarify that this refers to the active minus silence condition? Again though, perhaps it would be more interesting to see correlations between the active and scientific control?\n\nDiscussion:\nThe first few sentences of the Discussion do not seem to be relevant to the main discussion and should be deleted: Taking Salopek’s “slow journalism” concept as a model [he makes a 21,000 mile-long journey (33.780 km) by foot, to retrace the pathways of our ancestors, the first humans who migrated from Africa and journeyed around the Earth - he posits that one must devote time to inter-personal connections in order to fully comprehend the human phenomenon - “Out of Eden Walk,”35], we consciously stood for the concept of “slow science” for a slow pace of methodology. In the Discussion, the authors refer to the auto-control setting. Can the authors clarify what they mean by this? It is not clear why the SHoRT trial is being used for comparison since this was a study of children. It seems that the design is completely different as well focusing on artistic components rather than spiritual. This should either be deleted or expanded more to clarify why this is an appropriate study for comparison. The authors state that the intervention was designed to elicit positive emotions, but may have resulted in other emotions as well. The authors should review articles on positive emotions and immune function. In addition, there should be greater clarification of what other emotions were elicited. Did they acquire data for this?\nCan the authors clarify the following passage? What do they mean by a “guiding principle”? however, the correlation of these changes with the fMRI-s indicated that even when biblical readings did not appear to have a physiological effect, they could have an ordering, arranging effect, along some specific guiding principle, on a key parameter like the lymphocyte counts.\nIt is appreciated that the authors try to connect the angular gyrus to spiritual aspects of the experience, but this needs to be clarified in the Introduction as well. On the other hand, the authors state: Thus, the brain area involved in the correlation described above (gyrus angularis) could also be linked to the “Aha! moment”. Why is there suddenly discussion about an Aha moment when this has not been discussed before and there is no mention of it in the methods or results? This should probably be deleted. Can the authors clarify why there were few significant findings? Perhaps it would be better to discuss the meaning of the lack of significant findings. The entire last part of the Discussion beginning with the paragraph that starts: “When one is examining the effect of the Word of God on man,…” seems to be speculation, theology, and not based on the scientific results presented. This whole section should be deleted. While the goal of the authors is appreciated, it seems that the limitations of the article described above are substantial.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "7851",
"date": "23 Feb 2022",
"name": "András Béres",
"role": "Author Response",
"response": "First of all, thank you Andrew Newberg for accepting our invitation and becoming the first to openly peer-review this paper. Thank you for going through the article so thoroughly with us. This is to confirm that yes, it is the correlation between change in lymphocytes, and difference in activation between the active and the scientific control block that was significant (not between the active and the silence block; the abbreviation \"s\" refers to the \"scientific text\" 's block). This is also to clarify that main purpose of the study was to measure the potential immunological effects of personal interventions that are primarily intended to elicit positive emotions at the bedside, among patients lying in the hospital. In the everyday practice of a hospital, this practically translates to visits by artists for the child-, and by chaplains for the adult population. This explains why we can refer to these two, seemingly different interventions on the same page in this study. \"SHoRT\" Study examined the effect of artists among sick children, \"HEALING\" Study examined the effect of a chaplain among sick adults. The methodological challenge was that genuine meetings with chaplains in hospitals always contain a spontaneous (\"inspired\") element, the very creation of such authentic meetings is always based on the chaplain's intuition, and this spontaneous element has a major effect on the whole meeting - and hence on any immunological imprint, would there be any. This spontaneity and the large room left for the chaplain's inspiration reflects the original setting of the biblical times in which the \"Word of God\" was firstly said, when such meetings happened as a spontaneous act of the participants - i.e., this is how Jesus met people. Had we taken this spontaneous element out, we would have suffocated the very phenomenon of which we were trying to estimate the potential immunological imprint. This methodological decision to leave the spontaneous element in, does not affect the reproducibility of the study - to the contrary, by proposing the possibility of the meeting for EVERY patient available on a ward on the day of the measurement, by establishing a rough order for the visits (\"HEAL Score\") to help manage the time available, but by always leaving to the chaplain the final choice of the patient she intends to visit, and only asking the chaplain to include the same biblical passage in every spontaneous meeting: these are the ways this study proposes to be reproducible anytime and anywhere in the world. The question raised was whether meetings with a chaplain can elicit immunological changes in patients, IF these meetings are left as authentical, as spontaneous as they originally are. It is the determination of a concrete group of patients among which to choose, the instruction for the chaplain to remain spontaneous and the permanence of the concrete biblical passage read that are fixed. In contrast to the previous studies on praying and meditation, the main phenomenon that this study was focused on was the effect of a spiritual meeting - a meeting with the chaplain and through her, with the \"Word of God\". Thus, the phenomenon in focus in this study was not praying, but meeting. It is the religious sensibilities raised by the topic touched by this measurement, and to avoid any potential distorsions in the interpretation of the results that we found, that we felt obliged to include the theological viewpoint in the discussion of the results. I.e. the reader - believer or atheist - could later ask: WHY have we not measured more immunological changes, if the \"Word of God\" is believed to heal? And, if lymphocyte counts are correlated with an area of the brain involved in understanding words, does that mean that those who TRY to understand the biblical passage better, will have more healing lymphocytes? These are theological questions. Thank you for being with us on this journey. We hope that these clarifications will prove to be meaningful for you. We believe these are also the main topics the readers will possibly face while summing the article up in themselves. Based on the Editorial Team's suggestion, we will be waiting for additional peer review reports before starting on the article revisions, in which we will address all the issues raised in full detail. We hope these improvements will render the article acceptable for you."
},
{
"c_id": "7976",
"date": "21 Mar 2022",
"name": "András Béres",
"role": "Author Response",
"response": "We are now publishing a revised version (v3) of our article, in order to address your report in full detail. To this we would add that the Isaiah chapter was expected to be less known by the participants, since it is seldom quoted and most of the enrolled patients were not actively practicing their faith; the proposition raised in your report, to use a different control as neutral, and to read from some other passage of the Bible such as a listing of names, is very interesting. A potentially surprising twist to this idea is that such a list of names, as neutral as it seems to be from a grammatical point of view, is not neutral from a spiritual point of view. Indeed, central in Judaism and in Christian piety is the assumption that the whole Bible - and not just parts of it - is sacred, the emotionally exuberant and the less spectacular verses alike. Interestingly, then, even the listing of names could hold a deeper meaning in this context: in line with Hellinger's theory stating that our \"self\" cannot be conceived as an individual being, but our subconscious is deeply rooted in the soul of our family, that of our ancestors, in the wider sense of the whole family of mankind (1, 2), the recitation of ancient names is portent of deep memories, thus can be evocative, and has the potential to move the deepest layers of the collective subconscious. The interesting question is whether these potential effects can be measured with fMRI, and whether this additional spiritual content would only be perceived by the religious participants, or some unintended imprints would also be detectable among the atheists. What do you think? In the current measurement, the usage of a text without any spiritual content as control seemed more appropriate, to maximally differentiate it from the biblical reading used in the active block. The comparison of biblical passages with different emotional content during fMRI, as well as the more sensitive measurement of the immunological parameters (by means of flow-cytometry for example, a tool that we could not afford due to financial constraints) are lines along which further research could develop - but this already paves the way for a series of completely new measurements. References (1) Hellinger B: Rachel Weeping for Her Children: Family Constellations in Israel. Heidelberg, Germany: Carl-Auer-International; 2003. (2) Hellinger B: Peace begins in the soul: Family constellations in the service of reconciliation (C. Beaumont, Trans.). Heidelberg, Germany: Carl-Auer-Systeme Verlag; 2003."
},
{
"c_id": "8386",
"date": "23 Jun 2022",
"name": "András Béres",
"role": "Author Response",
"response": "Dear Andrew B. Newberg, We are now publishing a further revised version of the article \"Healing through faith: meeting a chaplain coupled with biblical readings could produce lymphocyte changes that correlate with brain activity (HEALING study)”, in order to fully address the concerns you articulated regarding Version1. Introduction Based on your advice, we have now clarified what our hypotheses were, what we were expecting to find in regards of changes in the immune response and the involvement of which brain areas could be anticipated. The truth is we intentionally started this clinical trial with as few preconceptions as possible, to remain open to any significant correlation that could emerge between the parameters we could afford to measure in a clinical setting – some of which are traditionally considered to correspond to the body, some others to the soul. Our measurement is a pilot study in this respect. Methods We have further clarified why the subjects were not randomized by chance, but by convenience i.e., depending on the availability of the chaplain on the days of the measurement (when the laboratory staff was available for the extra measurements and when the fMRI equipment could be used for the study). Allocating by chance would not have been a difficult option technically but could have resulted in significant distortions in the supposed psycho-immunological effects. Indeed, by the time the patients were classified as eligible and randomizable in this study, they represented this tiny portion of patients who were truly in need of a visit by the chaplain. The cancellation/postponement of the visit could have resulted in significant stress, disappointments, by which means the measurement method would have disproportionately influenced the parameters measured in the control group. In the intervention group, it was the chaplain who decided whom she wanted to visit among the patients who were randomizable. In the Discussion, we explain in detail why we opted for this methodological decision – the main goal was not to interfere with the genuine, authentic character of the chaplain-patient relationship that we were aiming to understand, and that always contains such a spontaneous element. The timing of the blood collections (30 minutes prior, and 60 minutes after the meeting) is now explained, it was based on the similar intervals used by previous, basic psycho-immunological studies that served as our starting point and that are mentioned in the Introduction (especially Berk et al., Bennett et al., Matsuzaki et al.). We believe the Isaiah chapter we used is, although not an entirely neglected, but a rarely used passage in religious practice, moreover, most of the patients enrolled were not actively practicing their faith. As to the usage of another biblical passage such as a listing of names for neutral control, we refer you back to our response in Version3 – even “neutral” passages can be portent of a “numinous” component. The contrast between a sacred passage intended to offer comfort, and a medical text with potentially fearful connotations was more marked, and therefore helped bring out the potential differences better. Part I Results Based on your suggestions, we have now significantly simplified this section and moved all the figures and tables containing null-results to the Extended data, so as not to overwhelm the reader with data that is non-significant. Also based on your suggestions we added data on effect size when there seemed to be a trend towards significance that might help developing further studies. Part II Results We have unambiguously clarified the meaning of the “a”, “s” and “c” abbreviations. There were no general differences that could be unanimously detected among all the patients, between the active prayer block and the control block, so hearing a religious recitation did not affect the brain differently than a neutral/scientific recitation, unanimously for all the patients enrolled in this study – but the main finding of the study is that a significant correlation between lymphocytes and brain activity emerged with the active minus scientific control block. This finding totally echoed previous psycho-immunological findings and is now highlighted in the Discussion. We hope your assessment of the statistical analysis being not appropriate was related to the confusing presentation of the null results, and that this issue is now fixed. The statistical tools used for interpretation, especially for fMRI evaluation are detailed in the Methods section and the Results part now is now limited to the precise description of the positive findings with some careful allusion to possible trends. We added the r value for the main correlation found. Discussion We left the reference to Salopek’s “Out of Eden Walk” in the Discussion but put it to the end of the first part, to show that this reference is meant to clarify the methodological decisions of the authors – a constant effort to produce authentic encounters at the bedside or in the chapel, even at the cost of a very slow pace of enrollment. We further illustrate this concept with the example of two patients whom we enrolled by proactively trying to overcome the special difficulties raised by their disabilities. Only a very personified study design could allow for this. Also, the term” auto-control” setting is now clarified in the text. It is particularly important that patients’ individual results are first compared to their own baseline values (difference in their own activation patterns during intervention and silence; difference in their own lymphocyte counts), in the context of a study using a cohort design, with many different patients enrolled. The SHoRT trial is used for comparison in the Discussion because either the artistic interventions for hospitalized children or the spiritual interventions for hospitalized adults were originally implemented in clinical practice with the implicit intent to elicit positive emotions among patients, to alleviate the burden caused by the disease. This is now explained in the Introduction, and based on your suggestion, the revised Introduction has been considerably enriched with additional key articles on positive emotions and immune function. These additional references help understand why the current study needed to put so much emphasis on proper patient selection, authenticity of the interventions; they also put the current study’s sample size, measured immune parameters, obtained p values, direction of change (increase or decrease) in perspective, as compared with similar basic studies. The revised Introduction also points towards a more nuanced approach to the visits by a person of faith, with a highlight on the religious undertones, and the revised Discussion also elaborates on that the intervention originally designed to elicit positive emotions, may have resulted in other emotions as well. The lymphocyte changes in the subgroup who received communion gives a striking example. The „Healing questionnaire” designed to record rough psychological aspects of the meetings, like emotional depth, perceived turmoil, correspondence with the chaplain as assessed by the participants… shows lines for further research, but the amount and length of questionnaires needed to be considerably restrained in the current setting, so as not to overwhelm the patients with documents to be completed - that could have interfered with the meetings themselves. As the Discussion acknowledges, the different emotional aspects of the spiritual experience in hospitals will need further research. The concept of a “guiding principle” having an arranging effect on the lymphocyte counts is now clarified in the Discussion. Based on your suggestion, we clarified in the Introduction how the angular gyrus could be involved in the spiritual experience, so that its appearance in the Discussion does not come across as a totally unexpected finding. Also based on your suggestion we deleted the allusion to the ‘Aha moment’ from the Discussion (correlations are possible but seem too remote to be dealt in detail in the Discussion of this study). Finally, although we keep the final part of the Discussion for the theological perspectives, we’d like to highlight that this section is called “Excursus”. We think it is always interesting to see how empiric observations relate to the way theology thinks about God. This is not meant as a substitute to replace the scientific discussion, but a way to complement it. We hope that with these significant revisions in the Discussion, your assessment regarding the conclusions as not having been drawn as adequately supported by the results is now changed. We are honored by your accepting to review this study. We honestly appreciate your reviewing it so thoroughly and hope our revisions have sufficiently addressed your concerns so that you now find the article acceptable from a scientific perspective."
}
]
}
] | 1
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https://f1000research.com/articles/10-1295
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https://f1000research.com/articles/13-864/v1
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01 Aug 24
|
{
"type": "Case Report",
"title": "Case Report: A male newborn with occipital horn syndrome",
"authors": [
"Marian K. H. Georgeos",
"Engy M. Hanna",
"Engy M. Hanna"
],
"abstract": "Occipital horn syndrome (OHS) is a rare genetic disease and copper transport disorder caused by a faulty ATP7A gene with multisystemic presentations, most originally related to musculoskeletal and connective tissue affections. In our case, a male neonate with OHS presented soon after birth with pathognomonic occipital exostosis, cutis laxa at the nape region, and widely opened skull sutures and fontanels. A skeletal survey showed occipital exostosis projecting from the line of insertion of the trapezius muscle and wide fontanels on skull X-ray films with no exostoses or deformities elsewhere. In addition to our case report being the second reported case for the condition detected early in the neonatal period, it also emphasizes the importance of investigating any sign thoroughly, as it may be an early alarming sign of a progressive disease that may affect the patient’s quality of life. In addition, it highlights the value of early diagnosis and multidisciplinary management of these patients.",
"keywords": [
"Occipital horn syndrome",
"ATP7A gene",
"cutis laxa",
"copper transport disorders",
"occipital exostosis",
"Menkes disease."
],
"content": "Introduction\n\nDespite the fact that copper is an element needed only for our body in minute amounts, any imbalance in its homeostasis will affect nearly all of our body systems. The entity “Copper transport disorders” comprises a disparate number of diseases including occipital horn syndrome (OHS, OMIM#304150) formerly called Ehler Danlos syndrome type IX or X-linked cutis laxa, and initially mentioned in the medical literature in 1975,1 beside classical Menkes disease (CMD), ATP7A-related distal motor neuropathy (DMN), and Wilson disease. The first three conditions result from a faulty ATP7A gene and lead to copper deficiency, while the latter is caused by ATP7B gene defects and leads to copper overload. The ATP7A gene is present on the long arm of the X-chromosome, band 13.3 (Xq13.3), extends for 140 kilobases, encodes a protein built up of 1500 amino acids, and weighs approximately 165 kDa. This gene is expressed in nearly all cell types, except hepatocytes.2\n\nMutations in this gene lead to either the formation of a distorted form of transmembrane copper transporting P-type ATPase protein or the cessation of its synthesis. ATPase plays a crucial role in copper homeostasis. Being a part of the trans-Golgi network (TGN), it helps to bring copper inside the Golgi network to be incorporated with copper-dependent enzymes; however, in cases of increased intracellular copper, this protein is mobilized to the cell membrane to help discard the excess. Copper-dependent enzymes include lysyl oxidase (LOX), which catalyzes the initial step of collagen synthesis. It also comprises the dopamine-β hydroxylase enzyme, which plays a role in the neurological and autonomic systems and helps form norepinephrine out of dopamine. Furthermore, it includes cytochrome C oxidase, superoxide dismutase, ascorbic acid oxidase, and tyrosinase.3\n\nAccordingly, a significant ATPase deficiency gives rise to Menkes disease, characterized by severe neurodevelopmental delay, but occipital horn syndrome occurs in the presence of a considerable amount of functioning protein. Despite being genetically related to the previous two diseases, ATP7A distal motor neuropathy, the third member of the ATP7A gene-dependent disease family, does not exhibit any similar biochemical or clinical manifestations besides neurological effects in the form of motor neuron disease.4\n\n\nCase report\n\nOur case report describes a male full-term neonate born at 39 weeks of gestation by spontaneous vaginal delivery to non-consanguineous parents. The APGAR scores were 8 and 9 in 1st and 5th minutes, respectively. The mother was 25 years old primi gravida. She attended antenatal visits regularly, and nothing was relevant to her medical history. Antenatal scans showed mild ventriculomegaly in the fetal brain.\n\nOn admission, the baby’s vital signs were stable, aside from being tachypneic (RR, 68). On plotting the body measurements on the growth chart, the weight was 2950 g (17th percentile), length was 50 cm (47th percentile), and head circumference was 32.5 cm (6th percentile).\n\nOn systematic head-to-toe review, multiple abnormal features were noted as follows: head inspection and palpation revealed bone protrusion projecting from the occipital area, roughly at the insertion of the trapezius muscle (Figure 1A), a widely opened anterior fontanel, sagittal suture, and metopic suture, even though the head circumference was on the lower side of the normal. Additionally, complete ankyloglossia and lax redundant skin folds of the nape were observed (Figure 2C).\n\n(a) shows the bony prominence projecting from the middle area of the occipital bone at the insertion site of the trapezius muscle. (b) the right hand of the patient shows a single transverse palmar (simian) crease. (c) shows lax redundant skin fold of the nape.\n\n(a) anteroposterior view showing widely opened anterior fontanel, sagittal suture, and metopic suture. (b) lateral view showing a bony prominence protruding from the occipital bone at the insertion site of the trapezius muscle (indicated by the white arrow) and redundant soft tissue at the nape.\n\nOn chest examination, the patient was tachypneic and could not maintain normal oxygen saturation without oxygen support. Regarding heart auscultation, normal heart sounds were heard in addition to a grade I diastolic murmur. Abdominal and limb assessments were normal, except for a single transverse palmar (simian) crease on the right hand (Figure 1B).\n\nThe baby was admitted to the SCBU for investigation of the multiple special features mentioned before, and because of respiratory distress, he received oxygen via a nasal cannula. The cause of respiratory distress was speculated to be transient tachypnea of the newborn (TTN), as the baby was successfully weaned to room air in less than 24 h, and the sepsis work-up did not show any positive markers of infection. In addition, the baby developed neonatal jaundice on day one of life, which was mostly due to ABO incompatibility and received phototherapy. On day three of life, the baby was discharged, and the family was referred to a genetic center for counseling.\n\nThe anteroposterior view of the skull radiograph showed widely opened sagittal and metopic sutures and fontanels (Figure 2A). Furthermore, a bony prominence protruding from the occipital bone was observed in the lateral view of the skull radiograph (Figure 2B). Moreover, cranial ultrasound revealed cerebral asymmetry, with the right hemisphere being slightly larger than the left hemisphere. In addition, a tiny patent ductus arteriosus (PDA) and a small atrial septal defect (ASD) were reported by echocardiography. Routine laboratory blood tests including sepsis work-up and kidney and liver functions were performed, all of which were normal except for high indirect hyperbilirubinemia. No genetic tests were performed on the patient because of the lack of resources in our facility.\n\nOn follow-up visits at the pediatric outpatient clinic, the mother reported recurrent attacks of bronchiolitis over the baby’s first six months of life.\n\n\nDiscussion\n\nThis is a noteworthy case report, as it is an extremely uncommon illness. To our knowledge, only 34 cases have been reported. Moreover, it is the first case diagnosed with occipital horn syndrome (OHS) in the Middle East, drawing the condition into the focus of healthcare personnel in this area and adding to the already known information worldwide.\n\nSymptoms and signs of OHS are not readily apparent at an early age. This was concluded from the diagnosis age of the previously reported cases, as only one case, other than ours, was identified in the neonatal period. The hallmark observed in our patient was the occipital horn, a bony prominence projecting from the occiput at the insertion area of the trapezius muscle. This resembles what was mentioned by Beyens et al. in their review of cases in which almost all cases had this sign.3 Fortunately, the mentality was mildly affected or unaffected at all, but this was very early to judge in our patient. In contrast to our patient, who had no obvious neurological problems, some reported cases exhibited hypotonia, developmental delay, and convulsions. In this context, most of the symptoms are related to connective tissue and musculoskeletal systems, which may progress to the extent of joint degeneration and movement difficulties. Regarding connective tissue manifestations, the majority of reported cases, including our case, presented with cutis laxa. Our patient had redundant skin folds in the nape region, which were suggested to be the remnants of the nuchal skin fold seen in antenatal ultrasound scans, although cutis laxa can occur in other places such as the face, chest, abdomen, or limbs. In agreement with Bonati et al., our baby had very wide sutures and fontanels.5 This could be explained by the presence of abnormalities in the formation of collagen and elastin. Similarly, patients can present with coarse hair, joint hypermobility and dislocations, pes planus, inguinal hernias, and large cephalohematoma. As for skeletal problems, patients can have bone aches, kyphoscoliosis, thoracic cavity deformities, genu valgum, and long bone deformities, in addition to restrictive elbow movement and these signs seem to worsen by time. Fortunately, our baby had nothing of the previously mentioned skeletal problems and this might be due to the early age of diagnosis. In addition, urological manifestations are widely recognized in OHS, such as recurrent urinary tract infections, which may be due to bladder diverticula or hydronephrosis. Furthermore, dysautonomia problems frequently occur, such as hypothermia and orthostatic hypotension, which may be severe enough to cause syncope and chronic diarrhea, resulting in failure to thrive. Less commonly, patients can exhibit the following life-threatening conditions: intestinal obstruction, arrhythmia, and apnea attacks.6–8 Moreover, our patient had signs that were not mentioned in any of the previously published cases as ankyloglossia and a single palmar crease.\n\nOn the other hand, most female members of the patients’ families are generally asymptomatic, apart from the pili torti reported in some cases.9\n\nA wide range of tests can be performed, including laboratory, imaging, molecular, and genetic tests. In terms of laboratory blood tests, patients with OHS are characterized by low serum levels of copper and ceruloplasmin. These tests are not very helpful in diagnosis at an early age because these levels are low by default in this period.9 CSF examination revealed high catecholamine levels.7 Fibroblast cultures exhibit increased intracellular copper.2\n\nImaging can aid in the diagnosis and follow-up of patients. In our case, skeletal survey revealed occipital exostosis. Bone exostosis may also exist in long bones near the joints, which may limit joint movement. Furthermore, osteopenia, osteoporosis, fractures, bowing of long bones, widening of the metaphysis and diaphysis, flat vertebra, and short clavicles have been reported.3 Pelvic and abdominal ultrasound should be performed annually to screen for bladder diverticula and hydronephrosis.9 Assessment of lung function clinically and by spirometry plays an important role in these patients for many reasons: first, for the early detection of asthma. Second, these patients may have a higher risk of developing chest infections, as highlighted by our patient’s mother, over the first few months of our patient’s life, and may have a higher incidence of obstructive and restrictive lung diseases, as reported by studies conducted for other types of cutis laxa patients.10 Cardiac investigations, including ECG, echocardiography, and MR angiography, are performed starting from puberty onwards, which may detect prolonged QT interval, mitral valve prolapse, and tortuous arteries such as hepatic, splenic, and cervical arteries, respectively. Predictably, echocardiography performed in our patient did not show any of these but only an ASD and a tiny PDA. Brain MRI may display cerebellar atrophy, delayed myelination, mild cortical atrophy, and convoluted intracranial arteries.3 In the same context, cranial ultrasound showed asymmetrical cerebral hemispheres in our baby. This could be due to mild cortical atrophy, but we suggest that this should be confirmed using MRI.\n\nExploring the root of the disease, genetically, the ATP7A gene is located on the X chromosome (Xq13.3), and it is an x-linked recessive disease, consequently affecting mainly male patients. ATP7A gene mutations leading to OHS were mostly splice-site and missense, and to a lesser extent frameshift, deletion, and deep intronic mutations (existing in a region more than 100 base pairs away from the intron-exon junction).3 Nonsense mutations were not found to be associated with this condition, and this may support the suggestion that the presence of 3-5% of wild-type transcripts may lead the patient to develop OHS rather than the more severe form of ATP7A mutations in classical Menkes disease.2 Unfortunately, genetic analysis was not performed in our patient because of unavailability at our facility. Genetic tests should be performed not only for the patient but also for his close relatives, especially the mother determining her carrier status, which may help to estimate the recurrence rate in future pregnancies.9\n\nOccipital horn syndrome partially shares some manifestations with other diseases included in its differential diagnosis. First, other copper transport diseases, especially Menkes disease, which is considered to be more severe genetic variant of OHS. The main point of distinction is that Menkes disease and ATP7A-related DMN manifest themselves with obvious neurological symptoms; the former leads to severe neurodevelopmental delay emerges at a young age while the latter appears in adulthood with a picture very similar to Charcot-Marie-Tooth disease, conversely, OHS shows mild neurological affection if any.9 Other forms of connective tissue diseases are added to the list of differentials, for example, FBLN5- and LTBP4-related cutis laxa, which share signs of redundant skin, urinary abnormalities such as bladder diverticula, and normal mentality; however, OHS is not associated with early onset emphysema, which is common with cutis laxa conditions. Furthermore, OHS has skin laxity in common with dermatosparaxis-type Ehler-Danlos syndrome (dEDS), but it lacks easy bruising, which is characteristic of dEDS. In addition, multiple congenital exostoses can be confused with OHS, whereas multiple exostoses manifest exclusively with skeletal problems due to the development of bone protrusions, which may turn into osteosarcomas. In addition, it is autosomal dominant and affects both males and females equally.3\n\nThe management of OHS is not a straightforward task because of the wide range of systems affected in OHS and the unfamiliarity with the condition; hence, it is predictable that the management needs the cooperation of a multidisciplinary team and to be tailored individually. In fact, most of the trials of medication were performed on patients with Menkes disease, the severe genetic allele of OHS. The main goal is close follow-up and early detection of new presentations and complications and to address them properly. The main areas that should be covered at each follow-up visit are the assessment of the patient for dysautonomia symptoms, including blood pressure measurement to exclude orthostatic hypotension, history of fainting attacks, and dizziness. Furthermore, follow-up visits should include screening for urinary anomalies, and educational and developmental assessments. The team of healthcare professionals may include developmental pediatricians to customize an educational strategy, urosurgeons for dealing with bladder diverticula, and physiotherapists and orthopedists to provide medical care to improve musculoskeletal problems. Within the same frame, medicines can be administered to ease the patient’s life, first, antibiotic prophylaxis for urinary tract infection, and second, droxidopa, which is a synthetic precursor for norepinephrine and dopamine, which is proposed to help with dysautonomia symptoms. In addition, copper histidine can also aid in management, with the condition that it should be started well before the age of 3 years; thus, it is important to screen newborn babies for this condition. Kaler et al. suggested that copper histidine showed some benefit in improving neurodevelopmental outcome at the expense of connective tissue-related signs. This could be due to the difficulty of copper histidine joining the TGN to be integrated with cuproenzymes such as the LOX enzyme.2,9 In fact, none of the previous management methods were initiated at our facility with the expectation that it would be planned for the baby at the genetic center where we referred the case, and hopefully, it would be effective for our baby as he was diagnosed at a very early age.\n\nIn accordance with the information provided above, coping with OHS may be quite challenging without early diagnosis and proper management, and unfortunately, can lead to death. In the same context, Beyens et al., in their review of cases, suggested that the mortality rate was 14.7% and the mean age of demise was as early as 19.5 years old. The main causes of fatality were post-surgery apnea attacks, perforated guts, and complicated cephalohematomas with disseminated intravascular coagulopathy.4\n\nDespite all the available knowledge about the condition, many questions have yet to be answered. For instance, are the severity of the symptoms and the age of their onset related to the type of gene mutation or the level of the wild transcript of the protein? Can we use either of them as predictors of disease progression? We hope that more reports and research will be conducted in the future to resolve these issues.\n\n\nConclusion\n\nHere, we report the 35th case of occipital horn syndrome, a rare genetic entity in the medical literature. Subtle early presentations, which usually develop with age, may make diagnosis very challenging in early life. Reporting more cases, in addition to genetic counseling and screening for families with already diagnosed members, may encourage a better understanding of the syndrome, expeditious diagnosis, and prompt management.\n\n\nConsent\n\nWritten informed consent for the publication of clinical data and images was obtained from the patient’s parents.\n\n\nList of contributors\n\nEngy M. Hanna, Neonatal intensive care unit (NICU), King Fahad Medical City, Riyadh, KSA. Engymaher230276@gmail.com",
"appendix": "Data and Software availability\n\nNo data are associated with this article.\n\n\nAcknowledgment\n\nThe author deeply appreciates the parents’ collaboration.\n\n\nReferences\n\nPalmer CA, Percy AK: Neuropathology of occipital horn syndrome. J. Child Neurol. 2001 Oct; 16(10): 764–766. PubMed Abstract | Publisher Full Text\n\nKodama H, Fujisawa C, Bhadhprasit W: Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment. Curr. Drug Metab. 2012 Mar; 13(3): 237–250. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBeyens A, Van Meensel K, Pottie L, et al.: Defining the Clinical, Molecular and Ultrastructural Characteristics in Occipital Horn Syndrome: Two New Cases and Review of the Literature. Genes (Basel). 2019 Jul 12; 10(7): 528. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKaler SG, Packman S: Inherited Disorders of Human Copper Metabolism. Emery and Rimoin’s Principles and Practice of Medical Genetics. 2013; P. 1–21. Elsevier. Publisher Full Text\n\nBonati MT, Verde F, Hladnik U, et al.: A novel nonsense ATP7A pathogenic variant in a family exhibiting a variable occipital horn syndrome phenotype. Mol. Genet. Metab. Rep. 2017 Jul 13; 13: 14–17. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYasmeen S, Lund K, De Paepe A, et al.: Occipital horn syndrome and classical Menkes Syndrome caused by deep intronic mutations, leading to the activation of ATP7A pseudo-exon. Eur. J. Hum. Genet. 2014 Apr; 22(4): 517–21. Epub 2013 Sep 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZeid CA, Yi L, Kaler SG: Menkes disease and other disorders related to ATP7A. Clinical and Translational Perspectives on Wilson Disease. 2019; 439–447. Elsevier. Publisher Full Text\n\nKaczmarek A, Kasprzyk M, Koch A, et al.: Orthopaedic interventions in occipital horn syndrome: a rare case of mutation in ATP7A gene. Egypt. J. Med. Hum. Genet. 2022; 23. Springer Science and Business Media LLC. Publisher Full Text\n\nKaler SG, DiStasio AT: ATP7A-Related Copper Transport Disorders.Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 2003 May 9 [updated 2021 Apr 15]; 1993–2024. PubMed Abstract\n\nMutlu-Albayrak H, Emiralioğlu N, Damar Ç: Overview of the Pulmonary Manifestations in Patients with Autosomal Recessive Cutis Laxa Type IC. Pediatr. Allergy Immunol. Pulmonol. 2020 Dec; 33(4): 207–212. Epub 2020 Sep 30. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "314325",
"date": "29 Aug 2024",
"name": "Marwa Elsayed",
"expertise": [
"Reviewer Expertise pediatrics and 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\nThe article was good in many aspects as - It is a case report about one of the uncommon pediatric disorders Occipital horn syndrome (OHS) which is rarely seen all over the world. - The history was brief but included all the important details , examination findings were systematic and investigations including imaging scans were very demonstrative . However there are some incomplete details such as : - treatment and outcomes are not available as the patient was transferred to specialized center for treatment and follow up . - Genetic testing was not done due to unavailability at the facility Overall , the article is very beneficial to me as pediatricians and I think it will be for other pediatricians as it gives us data about one of the rare diseases and how to diagnose and treat\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": []
},
{
"id": "314318",
"date": "03 Sep 2024",
"name": "Małgorzata Lenartowicz",
"expertise": [
"Reviewer Expertise Metabolic disease",
"animal models of metabolic disease",
"copper and iron metabolism"
],
"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 a case of a patient with suspected occipital horn syndrome (OHS) the case is interesting because OHS is an ultra-rare genetic syndrome and the description of each patient here brings information to help build a better clinical picture of the disease. However a lot of clinical symptoms indicated that patient suffer from OHS caused by mutation in ATP7A gene but unfortunately it should be supported by genetical diagnosis. It can be much more interesting because as no case of this disease has been described in the patient's family so far and it can be a new mutation arised de novo.\n\nThe following issues that arose during the evaluation of the manuscript should be addressed.\nIntroduction\nI suggest making small change to this part of the text as follows: “Mutations in this gene lead to either the formation of a distorted form of transmembrane copper transporting P-type ATPase protein or the cessation of its synthesis. ATPase plays a crucial role in copper homeostasis. Being a part of the Golgi network (TGN), it helps to bring copper inside the Golgi network to be incorporated with copper-dependent enzymes include, lysyl oxidase (LOX), which catalyzes the initial step of collagen synthesis. It also comprises the dopamine-β hydroxylase enzyme, which plays a role in the neurological and autonomic systems and helps form norepinephrine out of dopamine. Furthermore, it includes cytochrome C oxidase, superoxide dismutase, ascorbic acid oxidase, and tyrosinase. However, in cases of increased intracellular copper, this protein is mobilized to the cell membrane to help discard the excess.” The case report\nPatient description should be more complete. Please add the information how the child was fed, and whether there were any problems with food intake eg. vomiting. Did the child have diarrhoea? Did the child urinate normally? What was the child's body temperature? Authors state that there was no change in the baby's blood analysis results, which is interesting as neonatal jaundice occurred very early. On which day of the child's life was blood drawn for analysis? Discussion\nInformation regarding familial history of the patients “On the other hand, most female members of the patients’ families are generally asymptomatic, apart from the pili torti reported in some cases” should be included in the chapter “Case report” not in Discussion.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": [
{
"c_id": "12711",
"date": "30 Oct 2024",
"name": "Marian Georgeos",
"role": "Author Response",
"response": "I appreciate the helpful suggestions. In the latest version, I have addressed all the points mentioned, with the exception of the last suggestion regarding relocating the paragraph mentioned in the discussion section (On the other hand, most of female members of the patients' families are generally asymptomatic, apart from the pili torti reported in some cases). I decided to keep it in the discussion section because under the title of the case report introduction, we only discussed the chemical and genetic basis of the disease, without mentioning anything about the symptoms and signs. These were detailed under the discussion section, so I thought it would be less confusing for the reader to keep it there with the rest of the signs and symptoms."
}
]
}
] | 1
|
https://f1000research.com/articles/13-864
|
https://f1000research.com/articles/13-935/v1
|
20 Aug 24
|
{
"type": "Data Note",
"title": "Data on selfـــefficacy and its sources during the COVID-19 crisis: A Saudi auditor’s perspective",
"authors": [
"Ali Ali Al-Ansi",
"Saeed Rabea Baatwah",
"Mahfoudh Hussein Mgammal",
"Ali Ali Al-Ansi",
"Saeed Rabea Baatwah"
],
"abstract": "Background Auditors during COVID-19 experienced an unprecedented situation where normal audit activities became difficult to conduct. Moreover, COVID-19 forced auditors to introduce a new audit approach, “remote auditing,” which was not common in most audit firms and required the adoption of more advanced technologies. Overall, auditors during COVID-19 needed both cognitive and technical factors to deliver high-quality audits. Despite the challenges, research into how auditors dealt with these issues is limited, presenting an intriguing area of study.\n\nMethods This dataset provides insights into the Saudi auditor’s experience and beliefs regarding audit activities during COVID-19. Through an online survey, researchers collected data from 193 out of 417 registered auditors with the Saudi Organization for Chartered and Professional Accountants (SOCPA). The survey assessed the auditors’ self-efficacy in conducting audits during the pandemic, exploring its sources and potential moderating factors. Specifically, the dataset includes responses on eight items related to self-efficacy, 19 items covering the four common sources of self-efficacy (mastery experience, vicarious experience, social persuasion, and physiological/emotional states), and six items assessing virtual audit competency. Additionally, the dataset contains demographic information valuable for researchers analysing the relationship between auditor self-efficacy, its sources, and other influencing factors.\n\nConclusions Overall, the dataset included in this article may serve a broader audience and be useful in improving several stakeholders’ understanding of the effects of COVID-19 on auditors and how auditors assess their ability to adapt to the COVID-19 consequences. This research contributes to the existing body of knowledge by highlighting the need for auditors to adapt to new circumstances and adopt innovative approaches during challenging times, thereby ensuring the delivery of high-quality audits.",
"keywords": [
"COVID-19",
"sources of selfـــefficacy",
"selfـــefficacy",
"virtual audit",
"Saudi Arabia."
],
"content": "Introduction\n\nThe coronavirus of 2019 (COVID-19) is a health pandemic causing disruption in the lives of humans and corporate businesses. In this crisis, auditors were put in an unprecedented situation to deliver their audit activities, as they used to carry out most audit activities in the present, which became impossible during the pandemic due to social distance and homestay requirements (Baatwah & Al-Ansi, 2022). Although the COVID-19 crisis raised concerns about the quality of audits and increased the risk of material misstatement (Kniffin et al., 2020), there has been not much studies addicted to how accounting scholars have collectively contributed to our understanding of the challenges created by the COVID-19 (Mgammal, Al-Matari, & Bardai, 2022; Rinaldi, 2022). This data article describes external auditors’ status during COVID-19 in Saudi Arabia. In particular, this data article elaborates on auditors’ self-efficacy during COVID-19 and its traditional sources and the degree of proficiency in using virtual audits. Several groups, such as regulators, those using financial data, policymakers, and researchers, may be more interested in this data set.\n\n\nMethods\n\nThe Local Committee of Research Ethics at Shaqra University (HAPO- 01-R-128) has reviewed and evaluated this study on Wednesday 08 May 2024 in accordance with “the rules of research ethics on living organisms” and its executive regulations issued by King Abdulaziz City for Science & Technology (KACST) in 1443 AH.\n\nDue to COVID-19, several individuals and corporate businesses have experienced difficulties conducting their activities as they did prior to the crisis. Auditors are professional audit service providers facing greater challenges in conducting their audit activities (Mgammal & Al-Matari, 2021; Baatwah & Al-Ansi, 2022; Rinaldi, 2022). These challenges have raised doubts for several stakeholders about the ability of such professional providers to deliver high-quality services (Arnold, 2020). Thus, this dataset may be used to assess the status and factors that most likely helped the auditors overcome the challenges of COVID-19. In doing so, we surveyed external auditors from Saudi Arabia to assess four constructs related to auditors’ perceptions of the sources of self-efficacy, self-efficacy during COVID-19, and virtual audit proficiency. Specifically, the questionnaire targeted the 417 registered auditors of the 25 audit firms or offices with SOCPA as of April 2021. The questionnaire was shared by email to all registered firms, requesting each firm or office to distribute the questionnaire to all auditors. Between April and August 2021, researchers gathered data from 193 auditors in Saudi Arabia through an online survey, resulting in 193 usable responses.\n\nIn designing the questionnaire, we have extensively reviewed related prior research. For example, we used the social cognitive theory developed by Bandura [4] and adapted items from education studies (e.g. Usher & Pajares, 2009; Peura et al., 2021; Zhang, Zhu, & Su, 2023) to develop items related to self-efficacy and its traditional sources because studies on self-efficacy in the context of auditing are limited (Mohd Sanusi, Iskandar, Monroe, & Saleh, 2018). Furthermore, we referred to the analytical framework of Teeter, Alles, and Vasarhelyi (2010) to create items on virtual audit proficiency. Drawing on existing literature, we identified eight key areas to explore auditor self-efficacy during COVID-19. These areas were measured using eight statements on a five-point Likert scale ranging from “strongly disagree” to “strongly agree.” Similarly, we adapted existing measures for four other factors that influence self-efficacy: mastery experiences (3 items), verbal and social persuasions (4 items), vicarious experiences (3 items), and physiological and emotional states (3 items). These items also used a five-point Likert scale ranging from “strongly disagree” to “strongly agree.” Additionally, we developed six new statements to assess how well auditors can use advanced technologies in their work (virtual audit proficiency). These items were rated on a five-point Likert scale ranging from “rarely” to “always.” The specific wording of all items is provided in Tables 2 and 3. As with any survey study, we included a section providing general information or demographic attributes of the respondents. These include the audit firm’s position, age, education, experiences, the type of affiliated audit firm, and the type of clients. Table 1 reports the demographic attributes of the respondents.\n\nBefore sharing the questionnaire with the auditors, we have taken several steps to improve our instrument’s readability, validity, and reliability. First, we shared the questionnaire with four audit professors, four audit partners, and two senior auditors to measure the reliability and readability of the content. According to the comments and suggestions, we have amended the questionnaire. Second, given that the first draft of the questionnaire is in English, in consultation with experts, we translated the questionnaire into Arabic, as this is the mother tongue of most auditors in Saudi Arabia. Finally, we filled out all questionnaire items in a Google Form and created a Google Form link to be shared with auditors because social distance restrictions and the preference of individuals communicating remotely were common at the time of developing this questionnaire. All 25 registered audit firms in Saudi Arabia received the online questionnaire via email, using contact information obtained from the SOCPA website.1\n\nThis article presents data collected from 193 external auditors in Saudi Arabia between April and August 2021. The data, available as raw and filtered versions in a Microsoft Excel worksheet (.xls) and summarized in tables within this article, explores self-efficacy, its sources, and virtual audit competency during the COVID-19 pandemic. The dataset contains the responses of auditors in four major sections. The first section mainly focuses on the demographic characteristics of respondents, asking them to select one option from the multiple-choice answers. This section asked the respondents to indicate, for example, the type of affiliated audit firm, age, experience, type of auditee, and gender. Table 1 reports these features of the population and distribution of frequencies across the respondents.\n\nThe second section delves into auditors’ self-efficacy (SE) during COVID-19 through eight statements. Using a five-point Likert scale ranging from “strongly disagree” to “strongly agree,” respondents assessed their confidence in performing their duties during the pandemic. The third section explores the traditional sources that influence self-efficacy. Respondents rated their agreement with three statements related to mastery experience (ME), three statements related to vicarious experience (VE), four statements related to social persuasion (SP), and three statements related to physiological and emotional states (PE), all using the same five-point Likert scale. The final section in this dataset includes six items and focuses on auditors’ competency in using advanced auditing technologies (virtual audit proficiency, or VAP). Using a 5-point scale from “rarely” to “always,” respondents indicated how often they employ advanced technologies for financial statement audit activities in the questionnaire. The items of these constructs and the associated frequency distribution across the Likert-scale are reported in Table 2 and Table 3. We also include the overall response for each construct for each respondent in the dataset. Table 4 reports the descriptive statistics for each construct. The questionnaire was uploaded to the Mendeley Data Repository for more details.\n\n\n\n• Capital market authorities, standards-setting authorities, policymakers in firms, and the public can exploit this dataset to assess how external auditors responded to the COVID-19 crisis and how they faced doubts about delivering high-quality audits.\n\n• This dataset will be valuable for researchers interested in studying auditors’ self-efficacy in Saudi Arabia.\n\n• Researchers can use the dataset in this article to provide more insights into how auditors’ demographic attributes can moderate or explain the relationship between self-efficacy and its sources during COVID-19.\n\n• Targeting professional auditors in Saudi Arabia, this dataset provides a unique glimpse into an underexplored environment where socio-economic and cultural factors differ significantly from those prevalent in many other audit markets.\n\n• The dataset can be analyzed and/or compared with data from similar countries as a basis for future comparative studies of auditors’ self-efficacy.\n\nThe Local Committee of Research Ethics at Shaqra University (HAPO- 01-R-128) has reviewed and evaluated this study in accordance with “the rules of research ethics on living organisms” and its executive regulations issued by King Abdulaziz City for Science & Technology (KACST) in 1443 AH.\n\nConsent: Verbal informed consent was obtained from all participants due to the need for flexibility during the COVID-19 pandemic when face-to-face interactions were limited. The consent process, including the study’s purpose, voluntary participation, and confidentiality measures, was clearly explained to participants. This approach was approved by the Local Committee of Research Ethics at Shaqra University (HAPO-01-R-128) to ensure ethical standards. Participants were informed that they could withdraw from the study at any time without consequences.\n\n\nCredit author statement\n\nBaatwah, Saeed was responsible for the research methodology, data curation, and writing of the results and discussion sections. Al-Ansi, Ali contributed to the initial draft and provided review and editing support. Mgammal, Mahfoudh Hussein played a key role in conceptualizing the research, conducting the investigation, and editing the final manuscript.",
"appendix": "Data availability\n\nMendeley Data: Data on self-efficacy and its sources during the COVID-19 crisis: A Saudi auditor’s perspective, 10.17632/x92c46n2fw.4\n\nThe project contains the following underlying data:\n\n• Excel file 1 consists of filtered data for the variables for the questionnaire data sample.\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nMendeley Data: Data on self-efficacy and its sources during the COVID-19 crisis: A Saudi auditor’s perspective, 10.17632/x92c46n2fw.4\n\nThe project contains the following underlying data:\n\n• 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\nAcknowledgments\n\nWe express our heartfelt gratitude to the audit experts who provided valuable feedback on the questionnaire, including audit professors and experienced auditors. We are particularly indebted to Prof. Ehsan Almoataz for his generous assistance in sharing the questionnaire and actively promoting participation among auditors. Finally, we extend our sincerest thanks to all the auditors who participated in this study, as well as those who kindly assisted in its distribution. Your contributions have been instrumental in this research endeavor.\n\n\nReferences\n\nArnold C: Summary of COVID-19 audit considerations. International Federation of Accountants.2020. Retrieved March 1. Reference Source\n\nBaatwah SR, Al-Ansi AA: Dataset for understanding the effort and performance of external auditors during the COVID-19 crisis: A remote audit analysis. Data Brief. 2022; 42: 108119. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKniffin KM, Narayanan J, Anseel F, et al.: COVID-19 and the Workplace: Implications, Issues, and Insights for Future Research and Action.2020.\n\nMgammal MH, Al-Matari EM: Survey data of coronavirus (COVID-19) thought concern, employees’ work performance, employees background, feeling about job, work motivation, job satisfaction, psychological state of mind and family commitment in two middle east countries. Data Brief. 2021; 34: 106661. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMgammal MH, Al-Matari EM, Bardai B: How coronavirus (COVID-19) pandemic thought concern affects employees’ work performance: evidence from real time survey. Cogent Business & Management. 2022; 9(1): 2064707. Publisher Full Text\n\nMohd Sanusi Z, Iskandar TM, Monroe GS, et al.: Effects of goal orientation, self-efficacy and task complexity on the audit judgement performance of Malaysian auditors. Account. Audit. Account. J. 2018; 31(1): 75–95. Publisher Full Text\n\nPeura P, Aro T, Räikkönen E, et al.: Trajectories of change in reading self-efficacy: A longitudinal analysis of self-efficacy and its sources. Contemp. Educ. Psychol. 2021; 64: 101947. Publisher Full Text\n\nRinaldi L: Accounting and the COVID-19 pandemic two years on: insights, gaps, and an agenda for future research.2022.\n\nTeeter RA, Alles MG, Vasarhelyi MA: The remote audit. J. Emerging Technol. Account. 2010; 7(1): 73–88. Publisher Full Text\n\nUsher EL, Pajares F: Sources of self-efficacy in mathematics: A validation study. Contemp. Educ. Psychol. 2009; 34(1): 89–101. Publisher Full Text\n\nZhang B, Zhu J, Su H: Toward the third generation artificial intelligence. SCIENCE CHINA Inf. Sci. 2023; 66(2): 1–19. Publisher Full Text\n\n\nFootnotes\n\n1 The following Google Form link was shared with the auditors: https://forms.gle/ZB9Pw1GoTJjNY3uo9."
}
|
[
{
"id": "317075",
"date": "10 Sep 2024",
"name": "Che Siti Lazrina Md Lazim",
"expertise": [
"Reviewer Expertise Accounting and Education Technology",
"Small Medium Enterprises"
],
"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 detailed overview of the study on external auditors in Saudi Arabia during the COVID-19 pandemic. The study addresses a critical issue—how the COVID-19 pandemic impacted auditing practices and is highly relevant to the ongoing disruptions caused by the pandemic. The introduction clearly states the purpose of the study, which is to understand auditors' self-efficacy and proficiency with virtual audits during the pandemic. So, the introduction is well articulated. Then, the methods section demonstrates a thoughtful approach to designing the survey, including reviewing existing literature and adapting validated measures. The steps taken to ensure the validity and reliability of the questionnaire, such as consultations with experts and translation into Arabic, are commendable. The data description section is thorough, detailing the structure of the dataset and the types of information collected. The inclusion of demographic data and various constructs related to self-efficacy and virtual audit proficiency adds depth to the analysis. However, the phrase “there has been not much studies addicted to” should be revised to “there have not been many studies addressing.” Another issue to be suggested is to provide a brief overview of the impact of COVID-19 on auditing practices globally before focusing on Saudi Arabia. This would offer readers a broader context. While, the methods section could benefit from a clearer explanation of the survey's development process, including how the items were selected and validated to enhance transparency. There are some minor language inconsistencies and awkward phrasing that could be improved for clarity. For instance, “The Local Committee of Research Ethics at Shaqra University (HAPO- 01-R-128)” could be more seamlessly integrated into the text. Overall, this article is well-structured and provides valuable insights into the challenges faced by auditors during the COVID-19 pandemic. By addressing the minor issues related to clarity, detailed presentation of results, and ensuring all tables are properly included, the article would be even more effective in communicating its findings.\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": [
{
"c_id": "12520",
"date": "30 Oct 2024",
"name": "Mahfoudh Mgammal",
"role": "Author Response",
"response": "We are very grateful for the suggestions and concerns that we believe are insightful and will contribute to the quality of our data note. We are grateful for your appreciation of the potential value of our dataset. Thus, we are grateful to address your comments/suggestions as follows: Comment 1 However, the phrase “there has been not much studies addicted to” should be revised to “there have not been many studies addressing”. Response We are grateful for your insightful comment. To address this comment, we have revised this phrase as suggested (second paragraph in the introduction) as follows: Although the COVID-19 crisis raised concerns about the quality of audits and increased the risk of material misstatement, there have not been many studies addressing how accounting scholars have collectively contributed to our understanding of the challenges created by the COVID-19 (Mgammal, Al-Matari, & Bardai, 2022; Rinaldi, 2022). Comment 2 Another issue to be suggested is to provide a brief overview of the impact of COVID-19 on auditing practices globally before focusing on Saudi Arabia. This would offer readers a broader context. Response Thank you for pointing this out. As suggested, we have highlighted the impact of COVID-19 on auditing practices by sharing the concerns of auditing regulatory authorities, audit practitioners, and audit scholars (first paragraph in the introduction) as follows: The coronavirus disease 2019 (COVID-19) is a health pandemic that disrupts the lives of humans and corporate businesses. Hay, Shires, and Dyk (2021) advocate that the COVID-19 crisis is more likely to affect the auditing profession. In this crisis, auditors were put in an unprecedented situation to deliver their audit activities, as they used to carry out most audit activities in the present, which became impossible during the pandemic due to social distancing and homestay requirements (Baatwah & Al-Ansi, 2022). Furthermore, the COVID-19 pandemic requires audit firms across the world to revise their assessment of material misstatement risks (Al-Qadasi, Baatwah, & Omer, 2023). According to the International Auditing and Assurance Standards Board (IAASB) and the Financial Reporting Council (FRC), the COVID-19 pandemic has introduced new risks of material misstatements that require auditors to redesign their audit approaches and execute extensive efforts to reduce these risks (IAASB, 2020; FRC, 2020). Audit practitioners have also acknowledged several difficulties in conducting audit activities during the COVID-19 pandemic (PwC, 2020; KPMG, 2020). We have also added discussions highlighting more information on the Saudi setting that will enrich the suitability of using this setting (second paragraph in the introduction) as follows: The accounting and audit profession in Saudi Arabia has recently witnessed considerable development in regulatory frameworks and practices. For example, international accounting standards and international audit standards are references for firms and auditors to practice auditing and accounting activities. It also formulated an independent regulatory body, SCOPA, to develop and monitor auditing accounting practices in Saudi Arabia. However, similar to auditors in other countries, Saudi auditors experienced anomalies in conducting audit activities during the pandemic. Thus, several groups, such as regulators, those using financial data, policymakers, and researchers may be more interested in this dataset. Comment 3 While, the methods section could benefit from a clearer explanation of the survey's development process, including how the items were selected and validated to enhance transparency. Response We appreciate this insightful comment because we believe it adds value to our research. We have clearly indicated discretions on how the items of the instruments are developed (third and fourth paragraphs in the methods) as follows: In designing the questionnaire, we extensively reviewed the related prior research. For example, we used the social cognitive theory developed by Bandura [4] and adapted items from education studies (e.g. Usher & Pajares, 2009; Peura et al., 2021; Zhang, Zhu, & Su, 2023) to develop items related to selfـــefficacy and its traditional sources because studies on selfـــefficacy in the context of auditing are limited (Mohd Sanusi, Iskandar, Monroe, & Saleh, 2018). Furthermore, we referred to Teeter et al.’s (2010) analytical framework to create items on virtual audit proficiency. Given that the questionnaire items are used in prior literature from other domains, the adaption of these items involves wording modifications to fit the auditing context. However, the adaptation of these items was shared with professors and experienced audit partners. Drawing on existing literature, we identified eight key items to explore auditor selfـــefficacy during COVID-19. These items are measured using eight statements on a five-point Likert scale ranging from \"strongly disagree\" to \"strongly agree.\" Similarly, we adapted existing measures for the four factors that influence self-efficacy: mastery experiences (3 items), verbal and social persuasion (4 items), vicarious experiences (3 items), and physiological and emotional states (3 items). These items also used a five-point Likert scale, ranging from \"strongly disagree\" to \"strongly agree.\" In addition, we developed six new statements to assess how well auditors can use advanced technologies in their work (virtual audit proficiency). These items were rated on a five-point Likert scale ranging from \"rarely\" to \"always.\" The specific wording of all the items is provided in Tables 2 and 3. As in any survey study, we included a section providing general information or demographic attributes of the respondents. These include the audit firm's position, age, education, experience, type of affiliated audit firm, and client type. Table 1 presents the respondents’ demographic attributes. We have also added more elaboration on the process of collecting the data (second paragraph in the methods) as follows: We identified all registered Saudi auditors as our population framework. SOCPA, the accounting and audit profession regulatory body in Saudi Arabia, provides a list of registered auditors and their information. As of April 2021, the list of registered auditors includes 25 audit firms/offices associated with 417 auditors, including audit partners and audit managers. Thus, all registered Saudi auditors were our population in this study, and they all had the chance to participate in this study. Specifically, the questionnaire targeted 417 registered auditors of 25 audit firms or offices with SOCPA as of April 2021. The online questionnaire was shared by email with all registered firms requesting each firm or office to distribute the questionnaire to all auditors. To increase the number of participants, we emailed audit firms and offices with two gentle reminders. Between April and August 2021, researchers gathered data from 193 auditors in Saudi Arabia, comprising 46% of the entire population. We assigned two researchers to review all responses for incompleteness and for inappropriateness of answers. This review concluded that 193 responses were usable for analysis. Furthermore, the researchers verified the potential non-response bias issue by comparing the responses received in April with those received in August. Using a two-tailed t-test, the researchers found no variation in the responses across the two groups, suggesting the absence of this issue. Comment 4 There are some minor language inconsistencies and awkward phrasing that could be improved for clarity. For instance, “The Local Committee of Research Ethics at Shaqra University (HAPO- 01-R-128)” could be more seamlessly integrated into the text. Response Thank you for highlighting this concern. To address this comment, we have moved this statement to the end parts of this paper under section “Ethics and Consent Statement”. Furthermore, we have proofread the paper to improve the language and presentation (please check throughout the paper). Once again, we would like to thank you for your thoughtful and insightful comments and suggestions and hope that the current version of the manuscript meets your expectations."
}
]
},
{
"id": "317069",
"date": "13 Sep 2024",
"name": "Ines Kateb",
"expertise": [
"Reviewer Expertise Accounting",
"Auditing",
"IFRS",
"Governance",
"Financial reporting",
"CSR and Sustainability."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article explores Saudi auditors' self-efficacy during the COVID-19 pandemic, specifically focusing on their proficiency with virtual audits. The dataset includes responses from 193 auditors on self-efficacy, its sources (mastery experience, vicarious experience, social persuasion, and physiological/emotional states), and virtual audit skills. The article provides valuable insights into how auditors adapted to pandemic-related challenges, offering a unique dataset for researchers, policymakers, and capital market authorities.\nThe authors clearly justify the creation of the dataset by highlighting the unprecedented challenges auditors faced during COVID-19. The rationale is well-grounded, as the study addresses how auditors adapted to remote audits, a practice not commonly used before the pandemic. The study's focus on self-efficacy and virtual audit proficiency fills a gap in the literature.\nWhile the methods are generally appropriate, the article could improve by providing more detail on how the survey items were selected and validated. Additionally, more clarity on the statistical methods used for data analysis would strengthen the paper's technical soundness. The language inconsistencies also suggest that minor revisions could improve overall clarity. Recommendation: Provide more explicit details about the selection and validation of survey items. Clarify the methodology used for analyzing the dataset, including any statistical tests. Address minor language inconsistencies to improve readability.\nWhile the survey design is well-explained, further details are needed for full replication. Specifically, more information about the survey's development process, including how items were adapted from previous research and validated, would be beneficial. Additionally, details about how the data was processed post-collection are lacking. Recommendation: Expand on the survey development and validation process to enhance transparency. Include more specifics on data processing steps to facilitate replication.\nThe dataset is clearly presented and accessible. It is stored in a public repository, and the article provides a detailed breakdown of the variables, making it easy for other researchers to use. The accompanying tables and descriptive statistics further enhance the dataset's usability.\nTo make the article scientifically sound, the authors must address the lack of clarity in the survey's development and validation process, as well as improve the technical details surrounding the analysis methods. Minor language corrections would also enhance clarity.\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": [
{
"c_id": "12521",
"date": "30 Oct 2024",
"name": "Mahfoudh Mgammal",
"role": "Author Response",
"response": "We are very grateful for the suggestions and concerns that we believe are insightful and will contribute to the quality of our data note. We are grateful for your appreciation of the potential value of our dataset. Thus, we are grateful to address your comments/suggestions as follows: Comment 1 While the methods are generally appropriate, the article could improve by providing more detail on how the survey items were selected and validated. Response We are grateful for your insightful comment. To address this comment, we have improved our discussion on the development of the items and the process of data collection. For example, we have highlighted how the items are developed by documenting the main theory and the related literature (third and fourth paragraphs in the methods) and elaborated more discussion on the process of data collection (second paragraph in the methods) as follows: We identified all registered Saudi auditors as our population framework. SOCPA, the accounting and audit profession regulatory body in Saudi Arabia, provides a list of registered auditors and their information. As of April 2021, the list of registered auditors includes 25 audit firms/offices associated with 417 auditors, including audit partners and audit managers. Thus, all registered Saudi auditors were our population in this study, and they all had the chance to participate in this study. Specifically, the questionnaire targeted 417 registered auditors of 25 audit firms or offices with SOCPA as of April 2021. The online questionnaire was shared by email with all registered firms requesting each firm or office to distribute the questionnaire to all auditors. To increase the number of participants, we emailed audit firms and offices with two gentle reminders. Between April and August 2021, researchers gathered data from 193 auditors in Saudi Arabia, comprising 46% of the entire population. We assigned two researchers to review all responses for incompleteness and for inappropriateness of answers. This review concluded that 193 responses were usable for analysis. Furthermore, the researchers verified the potential non-response bias issue by comparing the responses received in April with those received in August. Using a two-tailed t-test, the researchers found no variation in the responses across the two groups, suggesting the absence of this issue. In designing the questionnaire, we extensively reviewed the related prior research. For example, we used the social cognitive theory developed by Bandura [4] and adapted items from education studies (e.g. Usher & Pajares, 2009; Peura et al., 2021; Zhang, Zhu, & Su, 2023) to develop items related to selfـــefficacy and its traditional sources because studies on selfـــefficacy in the context of auditing are limited (Mohd Sanusi, Iskandar, Monroe, & Saleh, 2018). Furthermore, we referred to Teeter et al.’s (2010) analytical framework to create items on virtual audit proficiency. Given that the questionnaire items are used in prior literature from other domains, the adaption of these items involves wording modifications to fit the auditing context. However, the adaptation of these items was shared with professors and experienced audit partners. Drawing on existing literature, we identified eight key items to explore auditor selfـــefficacy during COVID-19. These items are measured using eight statements on a five-point Likert scale ranging from \"strongly disagree\" to \"strongly agree.\" Similarly, we adapted existing measures for the four factors that influence self-efficacy: mastery experiences (3 items), verbal and social persuasion (4 items), vicarious experiences (3 items), and physiological and emotional states (3 items). These items also used a five-point Likert scale, ranging from \"strongly disagree\" to \"strongly agree.\" In addition, we developed six new statements to assess how well auditors can use advanced technologies in their work (virtual audit proficiency). These items were rated on a five-point Likert scale ranging from \"rarely\" to \"always.\" The specific wording of all the items is provided in Tables 2 and 3. As in any survey study, we included a section providing general information or demographic attributes of the respondents. These include the audit firm's position, age, education, experience, type of affiliated audit firm, and client type. Table 1 presents the respondents’ demographic attributes. Comment 2 Additionally, more clarity on the statistical methods used for data analysis would strengthen the paper's technical soundness. Response Many thanks for suggesting this to us. With due respect, we would like to note that this study reports more discerptions on the data by focusing on methods of collecting the data and the measurements of key variables. We have used basic statistical methods such as mean, standards deviation, max, and min statistics. Thus, given this nature, we do not use more advance statistics that are common in testing hypothesis. Nonetheless, we have now clearly articulate these statistics in addition to any relevant statistics for descripting the data (second paragraph in the Data Description and second paragraph in the Methods) Table 4 reports the descriptive statistics for each construct using basic statistics such as the mean, standard deviation, maximum, and minimum. Using a two-tailed t-test, the researchers found no variation in the responses across the two groups, suggesting the absence of this issue. Comment 3 The language inconsistencies also suggest that minor revisions could improve overall clarity. Response We really appreciate this insightful comment. To address this comment, we have proofread the paper and improve the presentation of the paper. We believe that the paper is now much improved. Comment 4 While the survey design is well-explained, further details are needed for full replication. Specifically, more information about the survey's development process, including how items were adapted from previous research and validated, would be beneficial. Additionally, details about how the data was processed post-collection are lacking. Response Thank you for pointing out this interesting comment because it is important to clarify the methods for replication this dataset. With due respect, we would like to note that we have improved our discussion on the development of the items and the process of data collection. As you can see in our response for the comment 1, we reported how this improvement is incorporated in the paper (please refer to our response for comment 1). Comment 5 To make the article scientifically sound, the authors must address the lack of clarity in the survey's development and validation process, as well as improve the technical details surrounding the analysis methods. Minor language corrections would also enhance clarity. Response Thank you for pointing this out interesting comment to us. With due respect, we would like to note that this comment summarized all comments/suggestions that raised before. In previous comments, we have tried our best to address these concerns and incorporated all these amendments in the paper. Thus, we will be grateful if you can refer to these previous comments and our responses. Once again, we would like to thank you for your thoughtful and insightful comments and suggestions and hope that the current version of the manuscript meets your expectations."
}
]
},
{
"id": "317074",
"date": "16 Sep 2024",
"name": "Jaizah Othman",
"expertise": [
"Reviewer Expertise Islamic banking and finance",
"credit risk",
"corporate governance",
"audit quality",
"financial reporting",
"financial derivatives",
"financial inclusion",
"risk management",
"behavioural finance",
"sustainability"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis study addresses a timely and relevant topic by examining Saudi auditors’ self-efficacy and proficiency in conducting virtual audits during the COVID-19 pandemic. This research provides valuable insights into how auditors in Saudi Arabia have adapted to the unprecedented challenges of the pandemic and thus fit well into global discussions on the disruption of professional practice. The aim of this study is clearly outlined and focuses on developing auditors' self-efficacy and remote auditing capabilities during this time. The data collection process has been clearly described. An online survey was conducted to obtain responses from 193 auditors registered with the Saudi Organization for Chartered and Professional Accountants (SOCPA). The inclusion of demographic data enriches the analysis and provides a deeper understanding of accountants' profiles and how these characteristics may influence their responses. In addition, the study complied with the ethical guidelines and was approved by the local research ethics committee at Shaqra University, and appropriate consent procedures were followed.\n\nHowever, there are some areas in which the study could be improved. An important improvement is to provide more details regarding the sampling method. It is unclear whether the 193 respondents were selected through random sampling or other methods. Clarifying this issue would improve the technical rigor and replicability of this study. The study also benefits from a broader contextualization of its findings. A brief discussion of the global impact of COVID-19 on audit practice before narrowing the focus to Saudi Arabia would help international readers better understand the relevance of the study in a broader context. In terms of replicability, although the methods are adequately described, additional details about the recruitment process and sample selection would help future researchers replicate the study. More transparency in these steps would increase the usefulness of this study for comparative research.\n\nFinally, the dataset is presented in a clear and accessible format. The tables summarizing the demographic data and key constructs are well-organized, and the availability of the dataset in a public repository (Mendeley Data Repository) adds significant value by enabling further research and comparative analysis. To summarize, while the study addresses an important and timely topic, it could be improved by methodological clarifications and a broader global context for its findings. These improvements would enhance the study's contribution to the understanding of the evolving role of auditors during the COVID-19 pandemic.\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": [
{
"c_id": "12522",
"date": "30 Oct 2024",
"name": "Mahfoudh Mgammal",
"role": "Author Response",
"response": "We are very grateful for the suggestions and concerns that we believe are insightful and will contribute to the quality of our data note. We are grateful for your appreciation of the potential value of our dataset. Thus, we are grateful to address your comments/suggestions as follows: Comment 1: It is unclear whether the 193 respondents were selected through random sampling or other methods. Clarifying this issue would improve the technical rigor and replicability of this study. Response: Thank you for pointing out this interesting comment because it is important to clarify the methods used for collecting the data. To address this comment, we have clearly articulated what is our population and how we reached the final number of participants (second paragraph in the Methods) as follows: We identified all registered Saudi auditors as our population framework. SOCPA, the accounting and audit profession regulatory body in Saudi Arabia, provides a list of registered auditors and their information. As of April 2021, the list of registered auditors includes 25 audit firms/offices associated with 417 auditors, including audit partners and audit managers. Thus, all registered Saudi auditors were our population in this study, and they all had the chance to participate in this study. Specifically, the questionnaire targeted 417 registered auditors of 25 audit firms or offices with SOCPA as of April 2021. The online questionnaire was shared by email with all registered firms requesting each firm or office to distribute the questionnaire to all auditors. To increase the number of participants, we emailed audit firms and offices with two gentle reminders. Between April and August 2021, researchers gathered data from 193 auditors in Saudi Arabia, comprising 46% of the entire population. We assigned two researchers to review all responses for incompleteness and for inappropriateness of answers. This review concluded that 193 responses were usable for analysis. Furthermore, the researchers verified the potential non-response bias issue by comparing the responses received in April with those received in August. Using a two-tailed t-test, the researchers found no variation in the responses across the two groups, suggesting the absence of this issue. Comment 2: The study also benefits from a broader contextualization of its findings. A brief discussion of the global impact of COVID-19 on audit practice before narrowing the focus to Saudi Arabia would help international readers better understand the relevance of the study in a broader context. Response: We thank you for commenting on this, and we are aware of the importance of adding more clarifications on the impact of COVID-19 on audit profession. To address this concern, we have added more discussions on the effect of COVID-19 on the audit (first paragraph in the introduction) as follows: The coronavirus disease 2019 (COVID-19) is a health pandemic that disrupts the lives of humans and corporate businesses. Hay, Shires, and Dyk (2021) advocate that the COVID-19 crisis is more likely to affect the auditing profession. In this crisis, auditors were put in an unprecedented situation to deliver their audit activities, as they used to carry out most audit activities in the present, which became impossible during the pandemic due to social distancing and homestay requirements (Baatwah & Al-Ansi, 2022). Furthermore, the COVID-19 pandemic requires audit firms across the world to revise their assessment of material misstatement risks (Al-Qadasi, Baatwah, & Omer, 2023). According to the International Auditing and Assurance Standards Board (IAASB) and the Financial Reporting Council (FRC), the COVID-19 pandemic has introduced new risks of material misstatements that require auditors to redesign their audit approaches and execute extensive efforts to reduce these risks (IAASB, 2020; FRC, 2020). Audit practitioners have also acknowledged several difficulties in conducting audit activities during the COVID-19 pandemic (PwC, 2020; KPMG, 2020). Comment 3: Additional details about the recruitment process and sample selection would help future researchers replicate the study. More transparency in these steps would increase the usefulness of this study for comparative research. Response: We thank you for pointing out this interesting comment, because it is important to add more validation to the dataset. To address this concern, we have expended the discussion on how the researchers recruit the data and describe the sample selection process (second and fifth paragraphs in the methods) as follows: We identified all registered Saudi auditors as our population framework. SOCPA, the accounting and audit profession regulatory body in Saudi Arabia, provides a list of registered auditors and their information. As of April 2021, the list of registered auditors includes 25 audit firms/offices associated with 417 auditors, including audit partners and audit managers. Thus, all registered Saudi auditors were our population in this study, and they all had the chance to participate in this study. Specifically, the questionnaire targeted 417 registered auditors of 25 audit firms or offices with SOCPA as of April 2021. The online questionnaire was shared by email with all registered firms requesting each firm or office to distribute the questionnaire to all auditors. To increase the number of participants, we emailed audit firms and offices with two gentle reminders. Between April and August 2021, researchers gathered data from 193 auditors in Saudi Arabia, comprising 46% of the entire population. We assigned two researchers to review all responses for incompleteness and for inappropriateness of answers. This review concluded that 193 responses were usable for analysis. Furthermore, the researchers verified the potential non-response bias issue by comparing the responses received in April with those received in August. Using a two-tailed t-test, the researchers found no variation in the responses across the two groups, suggesting the absence of this issue. Before sharing the questionnaire with auditors, we took several steps to improve our instrument's readability, validity, and reliability. First, the questionnaire was shared with four audit professors, four audit partners, and two senior auditors to measure the reliability and readability of the content. Based on these comments and suggestions, we amended the questionnaire. Second, given that the first draft of the questionnaire was in English, in consultation with experts, we translated the questionnaire into Arabic, as this is the native language of most auditors in Saudi Arabia. Finally, we filled out all questionnaire items in a Google Form and created a Google Form link to be shared with auditors because social distance restrictions and the preferences of individuals communicating remotely were common at the time of developing this questionnaire. Furthermore, using a Google Form link is a common method for collecting data in survey-based studies as it is associated with less effort and fewer errors. Thus, all 25 registered audit firms in Saudi Arabia received an online questionnaire via email using contact information obtained from the SOCPA website. Once again, we would like to thank you for your thoughtful and insightful comments and suggestions and hope that the current version of the manuscript meets your expectations."
}
]
}
] | 1
|
https://f1000research.com/articles/13-935
|
https://f1000research.com/articles/13-1299/v1
|
30 Oct 24
|
{
"type": "Research Article",
"title": "A causality investigation into stock prices and macroeconomic indicators in the Indian stock market",
"authors": [
"Sanjay Singh Chauhan",
"Pradeep Suri",
"Debapriyo Nag",
"Farman Ali",
"Pradeep Suri",
"Debapriyo Nag",
"Farman Ali"
],
"abstract": "Background of the study The systematic impact of macroeconomic variables on stock market returns makes it crucial to comprehend the link between macroeconomic variables and the stock market. Stock prices are closely linked to macroeconomic indicators, a crucial aspect for investors, policymakers, and researchers in emerging markets like India, influencing investment decisions and policy formulation.\n\nMethods The autoregressive distributed lag (ARDL) model was used in this study to examine the causal links between specific macroeconomic factors and Indian stock prices from April 2009 to March 2023.\n\nResults The outcomes of the research suggest that macroeconomic variables exert influence on the Indian stock market, across the short and long term. Moreover, the results of the paired Granger causality test suggest that the domestic macroeconomic variables possess predictive significance for stock prices in the Indian stock market.\n\nConclusion The study reveals that macroeconomic variables significantly impact the Indian stock market, highlighting the need for investors and portfolio managers to monitor these conditions to optimize returns and mitigate risks. The Reserve Bank of India should maintain an optimal money supply to prevent inflation and exchange rate fluctuations, while bolstering the export sector and facilitating imports through initiatives like Atma-nirbhar Bharat Abhiyan and Make in India. Policies focusing on productivity, infrastructure, and a favourable business environment are also crucial. Therefore, it is crucial for investors and portfolio managers to consistently analyse the current macroeconomic conditions in order to maximize their profits and minimize risks. This research has extensive significance for comprehending the intricate connections between the stock market and macroeconomic issues.",
"keywords": [
"Indian Stock markets",
"Macroeconomic variables",
"Causal relationships",
"Stock prices",
"ARDL"
],
"content": "Introduction\n\nThe Indian economy is ranked tenth in terms of nominal gross domestic product (GDP), and the International Monetary Fund (IMF) reports that it is the third largest economy in the world in terms of purchasing power parity (PPP). Kumar et al. (2023) have observed a significant increase in the quantity and volume of investments made in the Indian stock market both domestic and foreign investors in the past two decades. One of the key elements of an economy is the stock market. Its significance lies in its ability to propel a nation’s economy forward. The stock market serves as a gauge of the health of the economy and a vehicle for capital formation. An efficient economy can be inferred from the presence of a robust banking system and a stock market that is consistently increasing in value (Kumari, 2011). The two primary functions of the stock markets are aiding in price discovery and offering liquidity. They facilitate firms in undertaking large-scale initiatives by enhancing the primary market. A strong stock market helps to stimulate the economy by facilitating efficient growth and saving, wise investment allocation, and the draw of foreign direct investment (FDI). Nevertheless, for the stock market to fulfil its vital role, it is imperative that it maintains a robust interaction with macroeconomic forces (Tripathi, V., & Seth, R. 2014).\n\nThe impact of economic fundamentals on stock returns or prices has been a topic of much discussion among experts and scholars. The Efficient Market Hypothesis, initially introduced by Fama in 1970, asserts that in a market that operates efficiently, investors would not achieve exceptional profits as stock prices fully incorporate all pertinent information regarding fluctuations in macroeconomic variables. If the Efficient Market Hypothesis is assumed to be valid, any fluctuations in macroeconomic indicators should not exert a substantial influence on stock returns. Nevertheless, subsequent studies conducted by Fama and Schwert (1977), Nelson (1976), and other researchers have conducted a thorough assessment of the findings derived from the Efficient Market Hypothesis. These studies have verified that macroeconomic factors do indeed have an impact on stock prices, consequently influencing stock returns. A further theoretical contribution to the link between stock prices and the fundamentals of the economy is the Arbitrage Pricing Theory (APT) (Ross, S.A. 1976; Chen et al., 1986).\n\nThe link between macroeconomic variables and the stock market has been extensively studied in recent studies, building on previously established theoretical groundwork. The relationship between macroeconomic variables, stock market returns, and development in Ghana was assessed by Asravor, R. K., and Fonu, P. D. D. (2021), offering insights that might be useful for developing nations like India. Luo, C., Qu, Y., Su, Y., and Dong, L. (2024) examine the transmission of risks from crude oil markets to China’s financial market, emphasizing the importance of crude oil prices, which are equally relevant for the Indian stock market.\n\nPrevious research highlights the significance of GDP, inflation, crude oil prices, exchange rates, industrial production, and interest rates as key macroeconomic factors that impact the stock market. Fromentin, V. (2022), Bildirici et al. (2022), Ediriweera and Dissanayake (2022), and Katmas and Indarningsih (2022) documented the importance of macroeconomic forces in international markets over time, whereas Yadav et al. (2022), Shadab, A., and Sinha, A. K. (2022), Rao, V., and Jyotreddy, K. (2022), or Kumar et al., (2023) provide evidence from the Indian market. The hypothesis that portfolio holder expectations about the future values of macroeconomic variables can impact stock prices and that these variables become risk factors when stocks are substituted for other assets in the portfolio is supported by the studies listed above. So, it is very important to look into how much macroeconomic indicator affect the stock markets.\n\n\nReview of literature\n\nMany studies have looked at how the stock market is connected to macroeconomic elements. Previous studies indicate that macroeconomic variables and the stock market have an association. Fama (1981) sought to examine the link between stock returns, economic activity, inflation, and money in order to question preconceptions and offer new viewpoints on the dynamics of equities markets. While stock returns and real factors including output, capital expenditures, and the actual rate of return on capital show a positive link, the research results show a negative link between money growth rate and inflation.\n\nNeifar et al. (2021) studied the relationship between macroeconomic indicators (currency rate, consumer price index, and interest rate) and the stock market in the United Kingdom. The ARDL model shows that there is a long-term symmetric link between macroeconomic data and the price of stocks. Conversely, the ECM representation’s results indicate that the UK stock price is rapidly advancing toward long-term equilibrium as a result of all of the macroeconomic variables that were assessed. According to Pole, H., and Cavusoglu, B. (2021), money supply and aggregate industrial output positively and significantly affect stock return volatility, whereas inflation and currency rates negatively affect it. This study used ARDL bonds to investigate the impact of macroeconomic variables on Nigerian stock market returns. Asravor, R. K., and Fonu, P. D. D. (2021) examined the connection between Ghana’s macroeconomic variables, stock market returns, and development revealed that interest rates and foreign direct investment were favourable to S.M. Development, but human capital, inflation, and money supply were awful. Using Jordan and Philips’ dynamic ARDL simulation model, Khan et al. (2021) studied exchange rate, gold, oil, and Shanghai stock exchange return effects. Although gold and oil prices positively affected return, the exchange rate negatively affected it. Chinese stock exchange rate fluctuations do not, in the long term, have a Granger-cause on stock returns, but they do have a substantial spillover effect, according to research by Cuestas and Tang (2021). Okorie et al. (2021) investigated the correlation between Nigerian inflation, currency rates, and stock market returns by employing copulas. It has been determined that there is a minor positive correlation between Nigerian inflation and stock market returns, as well as a positive association between Nigerian inflation and the exchange rate of the Nigerian Naira against the US dollar. Hung (2022c) investigates the dynamic connectedness between macroeconomic data and the Chinese stock market through wavelet coherence analysis. Short-term macroeconomic variables affect the stock market, whereas long-term stock gains improve macroeconomic conditions. Javangwe and Takawira (2022) examined the South African stock market and currency rates using ARDL. The stock market is found to be adversely affected by exchange rate fluctuations in the long term. Using ECM, Katmas and Indarningsih (2022) investigated at how inflation, interest rates, and foreign exchange rates impacted the Indonesian Sharia Stock Index (ISSI) and found that BI interest has a long-term effect on the index, exchange rates have both short- and long-term effects, and inflation has no effect. Economic growth variables and the time valve of money were the two components identified by Ediriweera and Dissanayake (2022) using factor analysis. The Time Value of Money component substantially affects the Colombo Stock Exchange, but Economic Growth has little effect. Bildirici et al. established a complex link between VIX investor mood, gold prices, currency rates, oil prices, and stock market returns in 2022. Nevertheless, the Turkish lira and energy prices have a significant influence on stock market returns. Fromentin (2022) employed the time-varying Granger causality framework to identify asymmetric bidirectional causation, which implies that the lead-lag relationship between macroeconomic variables and US stock price is subject to change over time.\n\nGay (2008) concluded that no significant link exists between exchange rates, oil prices, and stock market index prices in any BRIC country, so implying a weak form of market efficiency in Brazil, Russia, India, and China by using the Box-Jenkins ARIMA model to investigate the correlation between macroeconomic variables and stock market index prices in BRIC nations. Salisu et al. (2021) investigated the potential of stock return differentials to anticipate exchange rate fluctuations in the BRICS countries, thereby evaluating the validity of the uncovered equity parity (UEP) theory for these countries. For three BRICS countries—Brazil, India, and South Africa—the research found a positive association between stock return differentials and exchange rate returns; results for China and Russia were opposite. Hung (2022b) using the MGARCH-DCC and Wavelet Coherence Transform approaches investigated the temporal and frequency link between worldwide crude oil, gold prices, and financial markets in the BRICS countries. The BRICS stock and exchange markets have long-term influence on crude oil and gold variables; yet, in the immediate term, the international commodities market greatly influences the BRICS financial markets. Hung (2022a) investigated the dynamic relationship and volatility spillover effects between exchange rates and stock returns in five Central and Eastern European (CEE) countries (Hung Hungary, Poland, the Czech Republic, Romania, and Croatia) and identified bidirectional volatility spillovers between the two financial markets in Hungary, the Czech Republic, and Croatia during the pre-crisis period; a unidirectional spillover of volatility from the stock market to the foreign exchange market was observed. Atif et al. (2022) evaluated the correlation between stock returns, exchange rates, and crude oil in emerging markets. Panel Granger causality revealed that the relationship between stock returns and oil prices has grown stronger since COVID-19 was designated a pandemic. The oil market and currency rates are two other factors that have a beneficial impact on stock performance. Hashmi, S. M., and Chang, B. H. (2023) discovered the positive relationship between E7 stock market and macroeconomic variables. Lone et al. (2023) found that selected macroeconomic variables affect the stock markets of all BRICS nations except Brazil in the long term.\n\nPal, K., and Mittal, R. (2011) examined the relationship between Indian capital markets and macroeconomic indicators. The analysis found that inflation has a major impact on both the S&P CNX Nifty and the BSE Sensex, although only the former affects interest rates and the latter foreign currency rates. Kalra (2012) documented the Sensex and macroeconomic data link. The gold price, inflation rate, and foreign exchange rate have been regarded as the most important components in the development of Sensex forecast models. Singh (2014) found that while money supply and foreign investment favourably influence the Indian stock market, gold prices and currency values have a negative impact there. Gurloveleen and Bhatia (2015) discovered that the exchange rate and foreign institutional investors were significant factors after doing multiple regression analyses. Furthermore, there is no causal association between relevant factors and the average closing prices of BSE 500 manufacturing enterprises, according to the Granger causality test. Kotha and Bhawna (2016) found that money supply and inflation positively affect the Indian stock market return, whereas interest rates negatively affect it. Misra (2018) employed the Vector Error Correction Model (VECM) to analyse the BSE Sensex’s relationship with various macroeconomic variables, concluding that these variables, including money supply, inflation, interest rates, gold prices, foreign institutional investment, exchange rate, and the Index of Industrial Production, exhibited a long-term causal relationship with the Sensex. Mohanty et al. (2021) used the Auto Regressive Distributed Lag (ARDL) model to look into how macroeconomic factors affect stock market returns. While the unemployment rate and inflation have a negative effect, the Sensex is favourably influenced by the manufacturing to GDP ratio, debt to GDP ratio, US dollar, and GDP growth. Interest has a negative effect on share prices but a positive effect on consumer prices and industrial output, according to Syed (2021), who looked at how macroeconomic events affect Bombay Stock Exchange share prices. Bhattacharjee, A., and Das, J. (2021) employed the autoregressive distributed lag (ARDL) bounds testing approach and the pair-wise Granger causality test to examine the long- and short-term relationships between domestic macroeconomic variables and the equities market. The exchange rate, wholesale price index, and money supply lag exert a considerable short-term effect, while the money supply and foreign currency exchange rate significantly influence the Indian stock market in the long run. Yadav et al. (2022) identified a substantial relationship between macroeconomic factors and the Indian stock market price using Johansen cointegration and sought long-run equilibrium using VECM. Using the GARCH model, Shadab, A., and Sinha, A. K. (2022) found a positive link between exchange rate and BSE Sensex. Rao, V., and Jyotreddy, K. (2022) investigated the relationship between stock price and macroeconomic variables using the ARDL model and found that, in the long run, the relationship is negligible; but, in the short run, foreign institutional investment and inflation positively influence stock prices while exchange rate has negative influence. Kumar et al. (2023) used the NARDL model to find that crude oil prices positively affect the Indian stock market and negatively affect the exchange rate, but gold prices had no effect.\n\nThough past studies have examined the relationship, opinions and clarity on how macroeconomic events influence the market are lacking. Previous studies yield contradicting findings; some revealed positive associations while others revealed negative or none at all. Bhattacharjee, A., and Das, J. (2021) discovered no correlation. Although Tripathi, V., and Seth, R. (2014) discovered that the Wholesale Price Index had a favourable effect on the Indian stock market. While Syed, A. A. (2021) found negative influence of interest rate, further Bhattacharjee, A., and Das, J. (2021) reported no association. Furthermore, displaying varying results is the gold price; Bhattacharjee, A., and Das, J. (2020) found negative influence and later in 2021 found no correlation. Studies on exchange rates yield inconsistent results with Ratanapakorn, O., and Sharma, S. C. (2007) noting positive influence while Syed, A. A. (2021) recorded negative impact. Different conclusions highlight the complexity of the link between macroeconomic factors and stock market.\n\nIt is necessary to offer unambiguous understanding on the link between macroeconomic variables and stock market. Few chosen variables have been used in past research at a time combined effect of all these variables is not investigated. Using ARDL bonds test, we have investigated the link between macroeconomic variables and stock market to close these discrepancies. Using monthly data from April 2009 to March 2023, the influence and most important macroeconomic factors influencing the stock market return in India are investigated and identified.\n\n\nMethods\n\nIn this paper we have used monthly data from April 2009 to March 2023 to study the impact of Wholesale price index (WPI), Consumer price index (CPI), Index of Industrial Production (IIP), Gross Domestic Product (GDP), Foreign Exchange Reserve (FER), Exchange Rate (ER), Silver Price (SP), Gold Prices (GP), Brent Crude Oil Prices (COP), Gross Fiscal Deficit (GFD), Value of Imports (IMP), Value of Exports (EXP), Foreign Institutional Investors (FII), Repo rate (REPO), Interest Rate (Long Term 10 yr) (INT), Call Money Rate (CMR), Balance of Payment (BOP), Broad Money (M3) on National Stock Exchange returns (RNSE) (Table 1). The autoregressive distributed lag (ARDL) bounds testing approach is used to investigate long-term correlations between variables. Pesaran et al. created it in 2001. Time series that are neither stationary nor have a fixed order of integration can be fitted using the ARDL model, which is based on ordinary least squares (OLS).\n\nThe current study applied Pesaran et al. (2001) Autoregressive Distributed Lag (ARDL) model. This method is applied since it provides strong findings when the dataset is small and the variables show a mix of integration orders, that is, I(0) and I(1) variables. We must first make sure none of the variables are stationary at second difference before using the ARDL model. We investigate at which level variables are stationary using the Augmented Dickey-Fuller (Phillips & Perron, 1988). The null hypothesis posits the existence of a unit root, while the alternative hypothesis suggests stationarity.\n\nThe augmented Dickey-Fuller test conducts the regression analysis described below.\n\nFundamentally, it has a similar null hypothesis as the unit root test. That is, the coefficient of Y(t-1) is 1, implying the presence of a unit root. If not rejected, the series is taken to be non-stationary.\n\nADF test results assist ARDL application to investigate co-integration among the variables. If the variables are stationery at level Johansen cointegration test is appropriate to investigate the long-term relationship among the variables. The equation used in the present study to specify the ARDL model is as follows:\n\nWhere xtvector of regressors, yt dependent variable; α0 intercept; Δ is the first difference operator; αi represent short-run coefficient; δi represent long-run coefficient; p and q represent restricted lags and εt shows error term. The estimated F-statistic indicates that the variables are cointegrated, therefore assuming a long-term link between them, if it surpasses the upper bound critical value. The test is said to be inconclusive, on the other hand, if the F-statistic goes below the upper bound critical value but stays above the lower bound critical value. It follows from an F-statistic smaller than the lower bound critical value that the variables are not cointegrated. Should the ARDL limits test verify cointegration, the long-run coefficients and short-run parameters including the error correction term are next to be estimated (Shrestha, M. B. & Bhatta, G. R., 2018). We then evaluate the model’s dependability with several diagnostic tests. The functional form of the model is checked using Ramsey’s RESET test; heteroscedasticity is tested using Breusch-Pagan–Godfrey test; serial correlation between the residuals is tested using Breusch-Godfrey serial correlation lag range multiplier (LM); and CUSUM test checks the stability of the coefficients. We investigated the direction of short-term causality using the pairwise Granger causality test (Granger, C. W., 1969).\n\n\nAnalysis and Discussion\n\ntime series analysis, ascertaining the stationarity status is a crucial step. This study employed the Augmented Dickey-Fuller test to ascertain the stationarity status (Table 2). The ADF test results demonstrate that LnIIP, LnGDP, and LnFII are stationary at level, but the remaining variables in the study are stationary at first difference. At the level, the null hypothesis that the series possesses a unit root is rejected for LnIIP, LnGDP, and LnFII, while it cannot be rejected for the remaining variables in the study. Upon the initial differencing, all non-stationary series attain stationarity.\n\nSubsequent to establishing the stationarity of the variables, we employed the ARDL bounds test to investigate the presence of a long-run relationship among the variables.\n\nTable 3 presents the findings of the Autoregressive Distributed Lag Bounds Test for cointegration, indicating a significant long-term equilibrium link among the variables. The F-statistic of 7.117339, obtained from the test, exceeds the upper bound critical values at all conventional significance levels: 2.77 at 10%, 3.04 at 5%, 3.28 at 2.50%, and 3.61 at 1%. The null hypothesis of no cointegration is rejected, confirming a long-term link between the examined variables.\n\nThe long-run ARDL results shown in Table 4 show that money supply (M3), GDP, foreign institutional investment (FII), exports (EXP), exchange rates (ER), and crude oil prices (COP) has statistically significant effect on the stock price. LnM3, LnGDP, LnFII, andLnCOP have positive coefficients indicating that stock price rises follow from changes in these variables. Should M3, GDP, FII, and COP rise by 1% stock price, the respective increases will be 1.37%, 0.12%, 0.09% and 0.30%. By contrast, LnEXP and LnER have negative coefficients, meaning a negative effect on stock price. Regarding the money supply, the outcomes contradict Asravor, R. K., & Fonu, P. D. D. (2021) and line Pole, H., and Cavusoglu, B. (2021). For GDP results match Parab, N., and Reddy, Y. V. (2020) and Abu-Libdeh, H., and Harasheh, M. (2011). Further crude oil price results contradict (Abuoliem et al., 2019) but support Jain, A., and Biswal, P. C. (2016).\n\nWith coefficients of -0.306743, -0.7189 and -0.1094, respectively, the Silver Price (SP), repo rate (REPO) and consumer price index (CPI) show negative associations, significant at the 10% level. Other variables, such as the wholesale price index, long-term interest rates, imports, industrial production index, gold price, gross fiscal deficit, foreign currency reserves, call money rate, and balance of payments, do not have statistically significant long-term effects. The model’s constant term is significant, as indicated by its coefficient of -12.5241. These findings emphasize the significant influences on the future behaviour of the dependent variable, which include money supply, GDP, foreign institutional investment, exports, currency rates, and crude oil prices.\n\nThe error correction model results (Table 5) reveal the short-term dynamics and the pace of adjustment towards the long-run equilibrium. The highly significant and negative error correction coefficient implies that approximately 22.74% of the deviation from the long-run equilibrium is rectified within one month. Lag of stock price, value of import, and exchange rate has significant negative impact on stock price. Impact of foreign exchange reserve is positive and significant. Furthermore, the model demonstrates strong explanatory power, with an R-squared value of 0.677981, highlighting its robustness in capturing the interrelationships among the variables.\n\nTo check reliability of the short run estimates Ramsey RESET and Breusch–Pagan–Godfrey Heteroskedasticity Test to check the reliability the short run estimates and CUSUM plot to test stability of the model. The Ramsey RESET test yields an F-statistic of 0.075087 with a p-value of 0.7845, indicating no evidence of model misspecification. The Breusch-Pagan-Godfrey test for heteroskedasticity provided an F-statistic of 0.953374 with a p-value of 0.5367, suggesting the residuals exhibit homoscedasticity (Table 6). CUSUM plot presented in Figure 2 indicate that the model is stable and outcomes are reliable.\n\nGranger causality examined the significance of the coefficients of lagged yt, which are used as the explanatory variables for xt in the regression context. For a simple bivariate model, one can test the following equation:\n\nWhere Ho: y does not Granger causes x in the first regression equation and x does not Granger causes y in the second regression equation.\n\nResults of pairwise Granger causality test (Table 7) Indicate that there is bidirectional causality between IMP and NSE, FII and NSE, FER and NSE, COP and NSE signifying the presence of feedback mechanism between the variables. Unidirectional causality is identified between WIP and NSE, SP and NSE, GDP and NSE, EXP and NSE, ER and NSE. Result indicates No causality between REPO and NSE, M3 and NSE, INT and NSE, IIP and NSE, GP and NSE, GFD and NSE, CPI and NSE, CMR and NSE, BOP and NSE. Pairwise Granger Causality Test findings suggest that IMP, FII, FER, COP, WIP, SP, GDP, EXP and ER are helpful in stock price prediction in Indian stock market.\n\n\nConclusion and Recommendations\n\nThe ARDL bonds test validates the presence of an enduring connection between the variables. The ARDL model demonstrates that over a long period of time, the money supply (M3), gross domestic product (GDP), foreign institutional investment (FII), and crude oil prices (COP) have a substantial positive influence on the stock price. Conversely, exchange rates (ER) and exports (EXP) have a major negative impact. In the near term, there is a large negative correlation between the lag of stock price, value of imports, and exchange rate with stock price. However, the influence of foreign exchange reserves on stock price is positive. The diagnostic tests performed on the residuals to confirm the accuracy and consistency of the short-run parameters indicated no signs of serial correlation, heteroscedasticity, or misspecification. The findings of the paired Granger causality test indicate that the domestic macroeconomic variables have predictive value for stock prices in the Indian stock market. Therefore, it is important to closely watch these variables.\n\nThe study’s findings suggest that macroeconomic variables have an impact on the Indian stock market both in the short term and the long term. Hence, it is imperative for investors and portfolio managers to regularly monitor the prevailing macroeconomic conditions in order to optimize their returns and mitigate potential risks. Furthermore, the finding has significant policy consequences. A rise in the money supply has a beneficial impact on the Indian stock market by enhancing a firm’s capacity to produce and borrow. The Reserve Bank of India (RBI) should strive to maintain an optimal level of money supply by utilizing open market operations and monetary policy. This is crucial because an excessive amount of money in circulation can lead to inflation, which has a detrimental impact on the Indian stock market. Furthermore, the exchange rate has a detrimental effect on the Indian stock market. The Reserve Bank of India (RBI) should implement measures to mitigate fluctuations in the exchange rate. The Indian government should formulate policies to bolster the export sector and facilitate the import of diverse items. The Atmanirbhar Bharat Abhiyan and Make in India initiatives are remarkable endeavours in this context; yet, the effectiveness of these initiatives relies on meticulous execution. The positive impact of GDP underscores the significance of continuous economic expansion, necessitating policies that focus on improving productivity, developing infrastructure, and creating a favourable business environment. Enhancing the inflow of Foreign Direct Investment (FDI) and Foreign Institutional Investment (FII) can significantly enhance economic performance. This necessitates the establishment of a stable and conducive regulatory framework that is attractive to investors.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability statement\n\nThe underlying data related to the paper are available in figshare with the following citation and DOI: https://doi.org/10.6084/m9.figshare.27044473 (Sanjay Singh Chauhan et al., 2024)\n\nA causality investigation into stock prices and macroeconomic indicators in the Indian stock market © 2024 by Sanjay Singh Chauhan, Dr. Pradeep Suri, Dr. Debapriyo Nag, Dr. Farman Ali is licensed under CC BY 4.0 Attribution 4.0 International.\n\n\nReferences\n\nAbu-Libdeh H, Harasheh M: Testing for correl--ation and causality relationships between stock prices and macroeconomic variables the case of Palestine Securities Exchange. Int. Rev. Bus. Res. Pap. 2011; 7(5): 141–154.\n\nAbuoliem N, Nor SM, Matar A, et al.: Crude oil prices, macroeconomic indicators, and the financial sector in Jordan: Dynamic causes and responses. J. Int. Stud. 2019; 12(3): 131–146. 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Empirical Economics Letters. 2021; 20: 27–36.\n\nNeifar M, Dhouib S, Bouhamed J, et al.: The impact of macroeconomic variables on Stock market in United Kingdom.2021.\n\nNelson CR: Inflation and rates of return on Common Stocks. J. Financ. 1976; 31(2): 471–483. Publisher Full Text\n\nOkorie IE, Akpanta AC, Ohakwe J, et al.: Modeling the relationships across Nigeria inflation, exchange rate, and stock market returns and further analysis. Ann. Data Sci. 2021; 8: 295–329. Publisher Full Text\n\nPal K, Mittal R: Impact of macroeconomic indicators on Indian capital markets. J. Risk Financ. 2011; 12(2): 84–97. Publisher Full Text\n\nPal K, Mittal R: Impact of macroeconomic indicators on Indian capital markets. J. Risk Financ. 2011; 12(2): 84–97. Publisher Full Text\n\nParab N, Reddy YV: The dynamics of macroeconomic variables in Indian stock market: a Bai–Perron approach. Macroeconomics and Finance in Emerging Market Economies. 2020; 13(1): 89–113. 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Publisher Full Text\n\nSalisu AA, Cuñado J, Isah K, et al.: Stock markets and exchange rate behavior of the BRICS. J. Forecast. 2021; 40(8): 1581–1595. Publisher Full Text\n\nShadab A, Sinha AK: Return and Volatility Spillover Effects between the INR-USD Exchange Rate and BSE Sensex. Finance India. 2022; 36(3).\n\nShrestha MB, Bhatta GR: Selecting appropriate methodological framework for time series data analysis. J. Financ. Data Sci. 2018; 4(2): 71–89. Publisher Full Text\n\nSingh P: Indian stock market and macroeconomic factors in current scenario. Int. J. Res. Bus. Manag. 2014; 2(11): 43–54.\n\nSyed AA: Symmetric and asymmetric influence of macroeconomic variables on stock prices movement: study of Indian stock market. New Challenges for Future Sustainability and Wellbeing. Emerald Publishing Limited; 2021; pp. 319–339. Publisher Full Text\n\nTripathi V, Seth R: Stock market performance and macroeconomic factors: The study of Indian equity market. Glob. Bus. Rev. 2014; 15(2): 291–316. Publisher Full Text\n\nYadav MP, Khera A, Mishra N: Empirical relationship between macroeconomic variables and stock market: Evidence from India. Manag. Labour Stud. 2022; 47(1): 119–129. Publisher Full Text"
}
|
[
{
"id": "337233",
"date": "07 Nov 2024",
"name": "Baranidharan Subburayan",
"expertise": [
"Reviewer Expertise Dr. S. Baranidharan specializes in financial analytics",
"with a focus on stock market analysis",
"financial econometrics",
"and economic modeling. His expertise includes hedging strategies",
"derivative markets",
"and the application of econometric methods for financial risk management. Dr. Baranidharan is also well-versed in analyzing macroeconomic variables affecting financial markets",
"particularly within the Indian context. His research contributes to understanding asset pricing",
"market efficiency",
"and the practical applications of quantitative finance. With extensive publications",
"he actively explores innovations in finance education and data-driven decision-making."
],
"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\nYour analysis provides a strong foundation, examining both short-term and long-term impacts of macroeconomic variables on the Indian stock market. The findings hold significance for investors and policymakers, and you present a clear framework for policy recommendations. However, to further enhance the rigour, clarity, and scientific soundness of your study, consider the following constructive suggestions\n1. Clarify the Methodological Approach\nWhile using the ARDL model is appropriate, it would be beneficial to justify why this model was selected over other econometric techniques, especially for readers less familiar with time-series methodologies. Could you briefly discuss why ARDL is suitable for analyzing the relationships between non-stationary variables?\nThe diagnostic tests ensure the robustness of the model, yet further clarification on which specific tests (e.g., Breusch-Godfrey for serial correlation or Breusch-Pagan for heteroscedasticity) were used would enhance transparency. Detail the results and thresholds applied to interpret the presence or absence of statistical issues.\n2. Strengthen the Discussion on Causality and Interpretation While the Granger causality test is a useful tool for examining predictiveness, it does not confirm causation. A brief statement on this limitation would enhance scientific accuracy, as it would clarify that observed relationships may not imply a causal impact.\nThe findings suggest differing influences of variables like FII and COP in the short vs. long term. A deeper exploration of why these factors have opposing impacts over different time horizons could improve interpretative depth.\n3. Expand the Literature Review and Comparison Comparing your findings to those of similar studies in emerging markets or other Asian economies can underscore the unique or common effects of macroeconomic variables in the Indian context. Specifically, mention studies on how money supply, exchange rates, and FII impact stock prices in comparable economies, discussing any consistencies or contradictions.\n\nMany of the policy recommendations align with existing government initiatives. Strengthen this section by drawing connections with specific studies or historical examples where similar macroeconomic interventions (e.g., exchange rate management or increased FII) led to observable outcomes.\n4. Improve the Presentation of Results Visual representations (e.g., impulse response functions or time-series graphs of each variable’s impact over time) could improve the clarity of your results, especially for capturing short-run vs. long-run effects. Ensure that the significance levels (p-values) of each coefficient in the ARDL model are explicitly reported. This will allow readers to gauge the reliability of the findings on variables with high and low significance.\n5. Recommendations Section Greater Specificity The recommendation for RBI to control money supply is insightful but could be more actionable. Suggest specific measures that RBI could adopt to balance money supply without triggering inflation, perhaps by referencing open market operations or reserve requirements. Expand on your recommendation for export support by discussing concrete steps, such as incentivizing export-oriented sectors or adopting trade policies aligned with ‘Make in India’ and ‘Atmanirbhar Bharat’ initiatives.\n6. Address Potential Limitation Variable Selection and Omitted Variables: Mention any limitations related to variable selection, such as the exclusion of additional external factors like global economic events or investor sentiment, which could influence the stock market. Additionally, a brief statement on potential multicollinearity concerns would reassure readers of the model’s robustness. Acknowledge if there are any limitations in the data period that might affect generalizability, especially if there were any structural changes in the economy (e.g., policy changes, COVID-19). Essential Revisions for Scientific Soundness\nJustify the choice of the ARDL model, including brief references to other possible models. Provide precise details on the diagnostic tests and their results. Expand on limitations related to causality and variable selection. Include significance levels for ARDL coefficients in tables for transparency.\nImplementing these points will improve the article’s scientific rigour, ensuring that its findings and recommendations are well-supported and its limitations are transparently addressed.\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? No\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12810",
"date": "12 Nov 2024",
"name": "Sanjay Chauhan",
"role": "Author Response",
"response": "Respected Sir, With due respect I would like to thank you for your valuable suggestions which I will be incorporating once get access by F1000. Thanks and regards Sanjay Singh Chauhan"
}
]
}
] | 1
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https://f1000research.com/articles/13-1299
|
https://f1000research.com/articles/11-107/v1
|
27 Jan 22
|
{
"type": "Research Article",
"title": "Does the impact of medical publications vary by disease indication and publication type? An exploration using a novel, value-based, publication metric framework: the EMPIRE Index",
"authors": [
"Tomas Rees",
"Avishek Pal",
"Avishek Pal"
],
"abstract": "Background: The EMPIRE (EMpirical Publication Impact and Reach Evaluation) Index is a value-based, multi-component metric framework to assess the impact of medical publications in terms of relevance to different stakeholders. It comprises three component scores (social, scholarly and societal impact), each incorporating related altmetrics that indicate a different aspect of engagement with the publication. Here, we present an exploratory investigation of whether publication types or disease indications influence EMPIRE Index scores. Methods: Article-level metrics were extracted and EMPIRE Index scores were calculated for 5825 journal articles published from 1 May 2017 to 1 May 2018, representing 12 disease indications (chosen to reflect a wide variety of common and rare diseases with a variety of aetiologies) and five publication types. Results: There were significant differences in scores between article types and disease indications. Median (95% CI) social and scholarly impact scores ranged from 1.2 (0.3–1.6) to 4.8 (3.1–6.6), respectively, for phase 3 clinical trials, and from 0.3 (0.3–0.4) to 2.3 (1.9–2.6), respectively, for observational studies. Social and scholarly impact scores were highest for multiple sclerosis publications and lowest for non-small cell lung cancer publications. Systematic reviews achieved greater impact than regular reviews. Median trends in the social impact of different disease areas matched the level of public interest as assessed through Google search interest. Although most articles did not register societal impact, mean societal impact scores were highest for migraine publications. Conclusions: The EMPIRE Index successfully identified differences in impact by disease area and publication type, which supports the notion that the impact of each publication needs to be evaluated in the context of these factors, and potentially others. These findings should be considered when using the EMPIRE Index to assess publication impact.",
"keywords": [
"Altmetrics",
"bibliometrics",
"publication impact"
],
"content": "Introduction\n\nArticle-level measures of publication impact (alternative metrics or altmetrics) can help to inform the impact of a publication among different audiences and in different contexts. Although the journal impact factor (JIF) may help to identify journals with a high readership, it is widely recognised as being a poor indicator of the quality or impact of individual research articles1,2. We have previously described a novel approach to summarising altmetrics, the EMPIRE (EMpirical Publication Impact and Reach Evaluation) Index, which uses article-level metrics to assess the impact of medical publications in terms relevant to different stakeholders3. The EMPIRE Index provides component scores for scholarly, social and societal impact, as well as a total impact score and predictive reach metrics. It provides richer information than other commonly used metrics such as the Altmetric Attention Score or JIF, with societal impact being the most distinct component score.\n\nIt is widely recognised that publication metrics vary by discipline; to facilitate the comparison of publication impact across different disciplines, field-normalised citation impacts are frequently calculated4. Metrics also vary by publication type. For example, a study found that review articles in pharmacology journals received twice as many citations as original articles5. Here, we present an exploratory investigation of whether disease indications and publication types influence the average EMPIRE Index scores.\n\n\nMethods\n\nThis exploratory study investigated 12 disease indications, chosen to reflect a variety of common and rare diseases with a variety of aetiologies. Six of these were rare diseases, selected as a convenience sample of disease indications with which the authors were most familiar. No formal statistical power analysis was undertaken. However, we aimed for disease samples from approximately 1000 publications, which would enable publication type sub-analyses. The six rare disease samples were, therefore, pooled.\n\nRelevant publications were identified for each disease by the appearance of the disease name in the publication title. We limited the search period to items with publication dates between 1 May 2017 and 1 May 2018, to give sufficient time for metrics to accumulate while also minimising the time-dependent variation in metrics.\n\nThe searches were conducted on PubMed between 22 June 2020 and 3 July 2020, using the following search string:\n\n\"(2017/05/01\"[Date - Publication] : \"2018/05/01\"[Date - Publication]) AND \"<disease name>\"[TI]\n\nFor each disease, we conducted secondary searches for each publication type using PubMed tags for those of interest (i.e. the search string above and either “review”, \"systematic review\", \"clinical trial, phase iii\", “clinical trial” or \"observational study\"). Altmetrics were obtained for all publications from Altmetric Explorer and PlumX over the period 23 June 2020 to 11 July 2020. Altmetrics were assumed to be zero for any publication for which Altmetric Explorer did not return a result. We also obtained the journal CiteScore for all publications6.\n\nEMPIRE Index scores were calculated for all publications as described previously3. Briefly, selected altmetrics that compose the EMPIRE Index were weighted and aggregated to form three component scores (social impact, scholarly impact and societal impact), which were then summed to form a total impact score.\n\nEach disease area comprised a different mixture of publication types, which we expected could confound the analysis; multivariate analysis on such a heterogenous, non-normal and zero-inflated data set is problematic. Therefore, we opted to create standardised samples through random polling.\n\nA sample was created for each disease area with a standardised mix of publication types chosen to maximise the total number of publications retained (the standardised publication types [SPT] set). First, the two least common publication types (phase 3 clinical trials and systematic reviews) were excluded because of the high variation between disease areas and because they are largely subsets of other publication types (clinical trials and reviews, respectively). Although the observational studies publication type was only slightly more common than systematic reviews, it was retained as it was considered to be functionally very different from clinical trials and reviews. The proportions of each of the remaining three publication types were calculated for each disease set, as well as for the overall set. Publications were then trimmed from each disease set by random sampling, as needed, to match the proportions in the overall set. The trimmed publication sets formed the SPT set.\n\nSimilarly, each publication type comprised a different mix of diseases. A standardised disease areas (SDA) set was created by random sampling using a similar approach that ensured each publication type included the same mix of diseases, while maximising the total number of publications retained.\n\nTo provide an indication of public interest in each of these diseases, we downloaded weekly Google Trends data on relative interest over time for the period of interest for these diseases (May 1 2017 to May 1 2018). A score of 100 indicates the maximum interest in any week over the search period and across any of the search terms of interest. The year averages presented here are expressed relative to that maximum score.\n\nAs these analyses were exploratory, we primarily provide descriptive statistics and only minimal statistical analysis was undertaken. Intra-group differences were assessed using Kruskal-Wallis one-way analysis of variance, a non-parametric test for equality of population means (a significant result indicates that that at least one population median of one group is different from the population median of at least one other group).\n\n\nResults\n\nIn total, 20 577 publications were identified across the 12 disease areas7, of which 5825 (28%) were tagged with one of the publication types of interest (Table 1). Table 1 also shows the Google search interest for each of these diseases.\n\nGoogle search interest is the average weekly interest across the search period, and is a relative score 0–100 where 100 is the maximum score for any disease in any individual week.\n\nDLBLC, diffuse large B-cell lymphoma; MS, multiple sclerosis; NASH, non-alcoholic steatohepatitis; NET, neuroendocrine tumour; NSCLC, non-small cell lung cancer; SMA, spinal muscular atrophy; T2D, type 2 diabetes; TNBC, triple-negative breast cancer; TSC, tuberous sclerosis complex.\n\nThe numbers of publications retained in the SDA set used for publication type comparisons (i.e. with the same disease indication composition for each publication type) are shown in Table 2.\n\nMS, multiple sclerosis; NSCLC, non-small cell lung cancer; T2D, type 2 diabetes.\n\nMedian EMPIRE Index scores and CiteScores for each disease in the SDA set are shown in Figure 1 and Table 3. Mean EMPIRE Index scores, shown in Figure 2, broadly reflect the median scores. Statistical analysis indicated that there was some significant variation in the medians of each component as well as the total impact score and journal CiteScore. In general, the ranking of publication type is relatively consistent across different types of impact. Notably, phase 3 clinical trials had the highest median and mean scores, while observational studies had the lowest. Systematic reviews had higher impact than reviews. Most articles across all publication types had no societal impact, and significant differences in societal impact were driven by outliers. Of note, eight of the ten publications with the highest societal impact were clinical trials, and six of those were in non-small cell lung cancer (NSCLC).\n\nCI, confidence interval.\n\nCI, confidence interval.\n\nThe interactive version (online only, accessible here: https://s3.eu-west-2.amazonaws.com/ox.em/webflow/p29ieu21/chart1.html) also shows mean EMPIRE Index scores for each disease by publication type (full set).\n\nThe numbers of publications retained in the SPT set used for disease comparisons (i.e. with the same publication type composition for each disease indication) are shown in Table 4.\n\nMS, multiple sclerosis; NSCLC, non-small cell lung cancer; SPT, standardised publication types; T2D, type 2 diabetes.\n\nMedian EMPIRE Index scores and journal CiteScores for each disease in the SPT set are shown in Figure 3 and Table 5. Kruskall–Wallis testing indicated at least one significant pairwise difference in the total scores, each component score and journal CiteScore. Migraine and multiple sclerosis (MS) had the highest impact across social and scholarly component scores as well as the total impact score, while NSCLC and psoriasis had the lowest. Most articles across all diseases had no societal impact, with significant differences in societal impact driven by outliers. The eight publications with the highest societal impact were all important clinical outcomes trials (three in type 2 diabetes, three in NSCLC and one each in migraine and asthma).\n\nMS, multiple sclerosis; NSCLC, non-small cell lung cancer; T2D, type 2 diabetes.\n\nCI, confidence interval; MS, multiple sclerosis; NSCLC, non-small cell lung cancer; T2D, type 2 diabetes.\n\nMean EMPIRE Index scores for each disease in the SPT set are shown in Figure 4. The interactive version of Figure 4 (online publication only) also shows the mean EMPIRE Index scores by disease for each publication type (full data set). Mean scores do not show clear trends for differences between disease indications, although societal impact appears to be lower for asthma and MS, and higher for migraine than other diseases. The high societal impact for migraine was driven by review articles; 16 of the 23 migraine articles with societal impact scores above zero were review articles. The scholarly impact for rare diseases appears to be higher than for other disease areas, albeit with low confidence owing to small numbers of publications included.\n\nThe interactive version (online only, accessible here: https://s3.eu-west-2.amazonaws.com/ox.em/webflow/p29ieu21/chart2.html) also shows mean EMPIRE Index scores for each disease by publication type (full set). MS, multiple sclerosis; NSCLC, non-small cell lung cancer; T2D, type 2 diabetes.\n\n\nDiscussion\n\nThis analysis found that typical EMPIRE Index scores vary across both disease indications and publication types. These results provide valuable contextual information for interpreting EMPIRE Index scores and publication metric findings in general, for individual publications. For example, these findings can be used to help to understand whether a particular publication has notably high (or low) metrics.\n\nWe found considerable differences between disease areas, which broadly reflected public interest in the disease (as assessed through Google search interest). For example, the three diseases with the highest median EMPIRE Index scores, especially social impact, were migraine, MS and asthma; these also had the highest public interest. These differences were not observed in journal CiteScores, meaning that the disease areas with higher EMPIRE Index impact were not necessarily published in ‘high impact’ journals. NSCLC had low public interest (‘lung cancer’ as a general term was higher, but still lower than any of the other five major disease areas examined). Publications in NSCLC also had low median total impact scores, particularly in terms of social impact, despite being published in journals with higher median CiteScores.\n\nAlthough this suggests distinct differences between diseases in terms of publication impact, it should be noted that the period of interest was only a single year. The findings could therefore have been influenced by the completion of important clinical studies, which can vary from year to year across disease areas.\n\nA clear picture is seen for publication types, with phase 3 trials demonstrating much higher metrics than other types. The high impact of phase 3 clinical trials is to be expected, given that they are intended to provide practice-changing information. Systematic reviews had higher impact than general reviews; interestingly, this was despite being published in journals with similar median CiteScores. This likely reflects that the methodological approach to synthesising systematic literature reviews makes them more impactful. Observational studies had the lowest impact, suggesting observational analyses are still generally regarded as having lower interest.\n\nIn general, across both publication types and disease indications, median scores were higher for scholarly impact than for social or societal impact, while mean and maximal scores were broadly similar (or lower). This suggests that score distribution is more skewed for social and societal impact, with many papers generating little interest despite some scholarly impact.\n\nA key strength of this study is the use of an automated approach to identify a large pool of publications for analysis. However, the automated process used depends on the reliability of the underlying data. For example, disease areas were identified through a PubMed search on article titles, which may have excluded some relevant articles or included irrelevant ones. The PubMed search engine uses automatic term mapping, which usually makes the search more inclusive but can introduce inconsistencies8. Publication types were identified by metadata tags, but these can often be inconsistently applied or missing. It can also result in duplication; for example, some phase 3 clinical trial publications in our sample were also classified as clinical trials.\n\nIn conclusion, the EMPIRE Index successfully identified differences in impact by disease indication and publication type. This supports the notion that there is no universal gold standard metric for publications, and instead the impact of each publication needs to be evaluated in the context of the type of publication, disease area and potentially other factors. These findings should be considered when using the EMPIRE Index to assess publication impact.\n\n\nData availability\n\nFigshare: EMPIRE Index disease and publication type analysis. https://doi.org/10.6084/m9.figshare.17072435.v17\n\nThis project contains the following underlying data:\n\nSMA metrics unlinked 11Jul20.xlsx\n\nPsoriasis metrics unlinked 11Jul20.xlsx\n\nNSCLC metrics unlinked 5Jul20.xlsx\n\nNET metrics unlinked 11Jul20.xlsx\n\nNASH metrics unlinked 11Jul20.xlsx\n\nMS metrics unlinked 5Jul20.xlsx\n\nMigraine metrics unlinked 5Jul20.xlsx\n\nGoogle search interest (30Jul21).xlsx\n\nDLBCL metrics unlinked 11Jul20.xlsx\n\nAsthma metrics unlinked 5Jul20.xlsx\n\nTSC metrics unlinked 11Jul20.xlsx\n\nTNBC metrics unlinked 11Jul20.xlsx\n\nT2DM metrics unlinked 5Jul20.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "References\n\nHaustein S, Larivière V: The use of bibliometrics for assessing research: possibilities, limitations and adverse effects. In Incentives and performance: governance of research organizations. (eds. Welpe, I., Wollersheim, J., Ringelhan, S. & Osterloh, M.) Springer, Cham, 2015; 121–139. Publisher Full Text\n\nRaff JW: The San Francisco declaration on research assessment. Biol Open. 2013; 2(6): 533–534. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPal A, Rees T: Introducing the EMPIRE Index: A novel, value-based metric framework to measure the impact of medical publications. medRxiv. 2021. Publisher Full Text\n\nRuiz-Castillo J, Waltman L: Field-normalized citation impact indicators using algorithmically constructed classification systems of science. J Informetr. 2015; 9(1): 102–117. Publisher Full Text\n\nAmiri M, Michel MC: Do review articles boost journal impact factors? A longitudinal analysis for five pharmacology journals. Naunyn Schmiedebergs Arch Pharmacol. 2018; 391(9): 1033–1035. PubMed Abstract | Publisher Full Text\n\nScopus Citescore. Reference Source\n\nRees T: EMPIRE Index disease and publication type analysis. figshare. Dataset. 2021. http://www.doi.org/10.6084/m9.figshare.17072435.v1\n\nKang P, Kalloniatis M, Doig GS: Using Updated PubMed: New Features and Functions to Enhance Literature Searches. JAMA. 2021; 326(6): 479–480. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "121444",
"date": "10 Feb 2022",
"name": "José Luis Ortega",
"expertise": [
"Reviewer Expertise Bibliometrics",
"altmetrics",
"academic search engines",
"scholarly social networks"
],
"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 attempts to find impact differences between medical publications according to diseases and publication types. These differences are calculated according to a new indicator, EMPIRE Index. More than 20k publications were retrieved from PubMed about 12 diseases areas. The resulting publications were also grouped by publication type. Using the Kruskal-Wallis test, authors found that the EMPIRE Indicator produces some differences between publications according to diseases and type of documents. These results allow them to justify the utility of this indicator and its power to identify different types of impacts.\nHowever, the paper presents several weaknesses that impede my recommendation for approval. Next, I detail some problem points by section:\nIntroduction\nThe introduction is poor because it does not introduce the research problem properly. An introduction should explain why the research is necessary and what the problem is that the paper wants to address. Why is important to know that impact varies by disease or by publication type? Why is an indicator such as EMPIRE Index necessary?\nAuthors confound article-level with altmetrics. Many altmetric measures could be article-level metrics, but there are other article-level metrics (i.e. citations) that are not altmetrics. Author should revise the text and correct these statements.\nI do not see a key section in a scientific article: a literature review. Authors should include a section where they contextualize the research, explaining previous studies that had deal with this problem. Studies about new indicators, differences in the impact by subject or document type, different types of impacts, etc. Overall, authors should present other studies in the introduction that show why is important to know that a disease has more social or scholarly impact, or why some document types attract more citations or tweets. In short, more conceptual background. The paper includes only eight references, which illustrates the poor context of this research.\n\nObjective\nI think this section is the most important in a paper and it is missing in this manuscript. If there are not objectives, there are not research goals and a paper lacks sense. The final line of Introduction says: “Here, we present an exploratory investigation of whether disease indications and publication types influence the average EMPIRE Index scores.” Why do you want to know this? Why is important to know this? Authors should introduce a section for objectives where they explain the main objectives and secondary ones. It could be interesting to include some research questions that specify the aim of the paper.\nMethods\nAuthors should include more detail about the data extraction process in Altmetric and PlumX. Authors claim that they used Altmetric Explorer to retrieve 20k publications. How did you exactly retrieve the data from this site? Do you use the API endpoint? How do you obtain the data from PlumX?\nA key element in the paper is to test differences according to diseases and document types, but there is not any explanation about these typologies. For example, and about document types, what is the difference between “review” and “systematic review”? This part is key because the definition of groups and types influences the results, so it is very important to define the diseases and the typology of documents.\nAll the analysis relies on a new indicator, EMPIRE Index. In spite of the importance of this indicator in the paper, there is not any information about how it is calculated and conceptualized. We have to read a non-peer reviewed pre-print deposited in a repository to know what it is. I do not see this way to do science as correct. Authors have to explain how this indicator is calculated in this paper; how the three component scores are defined; what is the difference between “social impact” and “societal impact”, mainly from a conceptual point of view; likewise how do you find three components and not two or four; which metrics take part in each component and why?\nCiteScore is an indicator for journals, not for articles. How it is used and why? The same for Google Trends - how they are used in the study, and why?\nResults\nTables 3 and 5 use CiteScore median for valuing articles by diseases. I recall that it is not correct to use journal indicators for research articles, and the use of median or mean from a ratio (CiteScore is the ratio of citations by publications) is a mathematical artifact, and the results are spurious.\nDiscussion\nThis paper lacks of any substantial discussion about the results. Sometimes the interpretation is obvious and it does not contribute valuable information. For example, the first paragraph ends: “For example, these findings can be used to help to understand whether a particular publication has notably high (or low) metrics.” This is obvious and It is not necessary to do this study to reach that conclusion. Every publication has high or low metrics. Another example: “Observational studies had the lowest impact, suggesting observational analyses are still generally regarded as having lower interest.” If they have low impact, then they have low interest.\nIt is interesting that the results from the EMPIRE index are not interpreted. For example, migraine, MS and asthma are the diseases with more social impact. Why? Is this positive or negative? Is there any evidence in other studies that confirm that these pathologies are more interesting for public audiences? For example, is there any correlation between these scores and Google Trends? Is there any survey that explore the public opinion about diseases? Etc.\nThis part should include the interpretation of the results according to the previous knowledge. It is interesting that this section only includes one citation (about using PubMed), but there is not any reference to previous results to discuss the validity of the findings or to explain the meaning of the results. For example, “The high impact of phase 3 clinical trials is to be expected, given that they are intended to provide practice-changing information.” Why is it that papers which provide practice-changing information should have more impact?\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "9407",
"date": "28 Apr 2023",
"name": "Tomas Rees",
"role": "Author Response",
"response": "We thank the reviewer for the commentary and perspective, and we have made numerous clarifications and additions to the manuscript to address these. One important caveat is that this is a F1000 Brief Report (https://f1000research.com/for-authors/article-guidelines/brief-report), and so is limited by the journal style template (no ‘Objectives’ section) and word count limit (2,500 words). It follows on from the full publication detailing the background and rationale of the EMPIRE Index published in PLOS ONE, which covers how it was developed and what the component scores signify. The current report is intended to provide some useful additional investigation of the properties of the EMPIRE index and its underlying article-level metrics. It is for these reasons that this report does not include a full literature review and does not go into the details of the EMPIRE Index that are covered in the PLOS ONE paper. We originally referenced the preprint in the current submission (the primary publication had been approved but publication was delayed) but have updated the reference now that the original article is fully published. We have addressed the reviewer’s other comments, as follows: We expanded the introduction to provide greater clarity of the objectives and purpose of this analysis – including why we have used CiteScore and Google Trends. We have added information on data extraction from Altmetrics Explorer and PlumX. We have also added information on the definition of the publication types (these are defined by PubMed). While most of the component metrics of the EMPIRE Index are altmetrics, article citations are not and we agree that using altmetrics as an umbrella term is therefore inappropriate: we have changed to article-level metrics (ALMs) throughout. We agree that computing an average CiteScore would be inappropriate, because such an average would not indicate the average number of citations per paper across the set of journals and so could be misleading. However, in our analysis we use the median, which is robust in this case since it does not transform the underlying data. We do not believe that it is obvious whether the metrics for a given paper are notably high or low. This can only be understood by understanding the typical metrics of comparable publications, which is the objective of this report. We note in the discussion that the higher scores of migraine publications, in particular social scores, may be linked to higher public interest as evidence by higher Google Trends interest. However, we acknowledge that the analyses presented do not and cannot explain the differences in typical scores seen across therapy areas and publication types. Therefore, any such discussion must necessarily be speculative and as such we keep it to a minimum. The sole purpose of this report is to demonstrate that these variations exist and to explore the magnitude of these variations. The analyses presented are robust and do provide meaningful results that address the objective. We therefore believe that the current, amended report is worthy of publication despite its brief nature."
}
]
}
] | 1
|
https://f1000research.com/articles/11-107
|
https://f1000research.com/articles/11-801/v1
|
18 Jul 22
|
{
"type": "Case Report",
"title": "Case Report: Smoking as the risk factor of persistent STEMI after primary percutaneous coronary intervention: how it could be happen?",
"authors": [
"Yusra Pintaningrum",
"Ricky Setiadi Yusuf",
"Baiq Hanida Aolia Ramdani",
"Shadiqa Rana Putri",
"Dwi Astuti Wulandari",
"Baiq Hanida Aolia Ramdani",
"Shadiqa Rana Putri",
"Dwi Astuti Wulandari"
],
"abstract": "Background Acute coronary syndrome (ACS) is a common disease. Smoking may increase the risk of ACS. The most advantageous therapy is percutaneous coronary intervention. This therapy may fail which is no-reflow phenomenon as the result.\n\nTotal occlusion may increase the risk of no-reflow phenomenon which it could be worse with smoking as the habits. ST-elevation myocardial infarction (STEMI) may show in electrocardiogram (ECG).\nCase description A 37-year-old male came to the hospital with chest pain as the main complaint. ECG examination showed that there was wide anterior STEMI. Coronary angiography was then done and confirmed that there was total occlusion in left anterior descending artery. After two days hospitalization, the patient developed to cardiogenic shock and lead to acute decompensated heart failure. An ECG showed there was STEMI anterior after primary PCI.\nDiscussion Many chemicals agent contain in cigarette smoking and it may induce the lipid oxidation which leads to plaque deposits. Plaque that deposits in coronary artery may rupture and make thrombus occlusion. This occlusion may partial or total, when there is total occlusion, STEMI was the result. Then, releasing the occlusion is needed for this situation ant PCI may be chosen as the therapy. Patient with wide ischemia may result the no-reflow phenomenon which may lead to heart failure and shock cardiogenic as the complication.\nConclusion Smoking may induce ACS which leads to STEMI and may increase the failure of PCI therapy. No-reflow phenomenon is the evidence of miscarriage in therapy which it may increase because of smoking.",
"keywords": [
"Smoking",
"no-reflow phenomenon",
"STEMI"
],
"content": "Introduction\n\nSince the early 1960s, the association between smoking and cardiovascular disease (CVD) has been explored in the Framingham Heart and the Seven Countries studies.1 About 26% of ACS patients were active in smoking at hospital administration until one year forward follow-up.1 Acute coronary syndrome (ACS) is one of many CVDs that commonly happens.2 Patients with ACS may develop total occlusion in coronary artery, so ST-elevation myocardial infarction (STEMI) as a result in ECG (Electrocradiogram).3 Percutaneous coronary intervention (PCI) is considered the most promising and rewarding reperfusion strategy.2 The failure in restoring myocardial reperfusion is mostly because of the no-reflow phenomenon.2 The incidence of this phenomenon is about 10–54% of procedures.2 This case report will discuss the correlation between smoking and the no-reflow phenomenon and how it can occur.\n\n\nCase report\n\nA 37-year-old male came to the hospital with severe chest pain as the main complaint. He is a high school teacher with no same medical or familial, or psychosocial history before. The patient said chest pain had occurred for about 3 hours before going to the hospital. He said that the pain was only in the middle of the chest, and was not reduced when resting. There are no other complaints besides chest pain. The patient said that he was a heavy smoker. In the hospital, we measured his vital signs: his temperature was 36.8°C, heart rate was 69 beats/minute, respiration rate was 23 breaths/minute, and blood pressure was 65/30 mmHg. The first electrocardiogram (ECG) was done in the hospital (Figure 1), and there was a wide anterior acute myocardial infarction (AMI). We gave oxygenation, Ringer Lactate infusion 250 mL, dopamine 4.2 mL/hour morphine 1 mg/hours, aspirin 400 mg, clopidogrel 300 mg, and omeprazole one ampule as the first treatment for the patient. After several hours, his blood pressure increased to 130/80 mmHg. Then, the patient was transferred to perform coronary angiography, which showed total occlusion in the proximal left anterior descending artery (LAD). Also, we inserted a stent to reflow vascularization of the heart. Chest radiography was also performed, and it did not show any abnormality (Figure 2). Blood examination was measured, and there was no abnormality.\n\nTwo days after percutaneous coronary intervention (PCI), the patient complained of chest pain again, the same as when he came to the hospital. Then, we performed ECG, which showed wide anterior AMI (Figure 3). After several hours the patient was unstable and fell into acute decompensated heart failure (ADHF) with cardiogenic shock. As the therapy, we combined dopamine and dobutamine five μg/kg/minute each to increase the patient’s blood pressure. Other supporting therapy was bisoprolol 2.5 mg/day, ramipril 2.5 mg/day, furosemide 20 mg/day, spironolactone 25 mg/day, atorvastatin 40 mg/day, aspirin 80 mg/day, nitroglycerin 20 μg/minute, and we changed clopidogrel to ticagrelor 90 mg/12 hours. Other supporting therapies were infusion with normal saline 500 mL/day, alprazolam 0.5 mg/day, Ivabradine 5 mg/12 hours, and ondansetron 4 mg/day. Thus, we also restricted water intake to between 1000–1200 cc/day. The echocardiography of the patient showed coronary artery disease (CAD) (Figure 4). After two days, the patient was in better condition, and the next day the patient was discharged from the hospital.\n\n\nDiscussion\n\nCigarette smoke contains about 4,000 different chemical agents considered the most complex and the least understood among cardiovascular risk factors of cardiovascular disease.3 Smoking-related cardiovascular dysfunction caused by toxic components in cigarette smoke has multiple mechanisms, including increased inflammation, oxidation of low-density lipoprotein cholesterol, platelet aggregability, thromboxane production, plasma viscosity, and fibrinogen levels. Smoking also causes alteration of the function of endothelial cells and reduces oxygen supply.4,5\n\nAs well as directly damaging coronary arteries, smoking also raises levels of harmful oxidized low-density lipoprotein and reduces beneficial high-density lipoprotein, thereby contributing to an increase in fatty deposits (plaque) at the site of the injury in the arteries. Smokers have higher extracellular lipid content in their plaque, which renders the plaque vulnerable to rupture. Endothelial injury and dysfunction promote platelet adhesion and lead to the formation of a blood clot: a process known as thrombosis. Tobacco smoking also induces a hypercoagulable state, increasing the risk of acute thrombosis. Smoking-mediated thrombosis appears to be a significant factor in the pathogenesis of critical cardiovascular events.4\n\nThe pathogenesis and risk factors of no-reflow are still incompletely understood. Several risk factors have been associated with the risk of a no-reflow phenomenon. Smoking is one of the risk factors for the incidence of the no-reflow phenomenon.6,7 However, several recent studies have shown that smokers have less reflow phenomenon after PCI. Data from Shemirani et al., showed that the incidence of the no-reflow phenomenon was not significantly different between smokers and non-smoker.2 This finding is still controversial. Theoretically, smoking is associated with the risk of CAD and endothelial dysfunction. Nevertheless, it has been described that the causes of no-reflow are multifactorial. Therefore, smoking cannot be judged as the only factor influencing no-reflow.6\n\nNo-reflow phenomenon (NRP) is the hypoperfusion of myocardial tissue after an occlusion is removed even though the epicardial coronary arteries are open and patent. NRP is quite common in patients who experience acute ST-elevation myocardial infarction (STEMI) and then receive primary percutaneous coronary intervention (PPCI).8–10 The process of how NRP happens has not been clearly described. It is said that many factors influence it, such as smoking, as in our case. In addition, the presence of leukocyte infiltration, vasoconstriction, activation of inflammatory pathways, and cellular edema is associated with the phenomenon of the occurrence of NRP.9,10\n\nBased on a study by Pantea et al., one-third of patients with NRP experience various complications.8,9 The presence of anterior STEMI and lesions in the left anterior descending artery (LAD) is associated with a high incidence of complications in these patients.8 Complications include hemodynamics disturbance, cardiogenic shock, myocardial rupture, pulmonary edema, heart failure, arrhythmias, and others.8,9 In this case, the patients develop cardiogenic shock and acute decompensated heart failure (ADHF). Cardiogenic shock results from long-term myocardial necrosis and secondary rupture of the free myocardial wall or interventricular septum.8 In addition, in NRP, heart rhythm disturbances occur, which cause ischemia in the long term, resulting in extensive necrosis of the heart myocardium. Furthermore, changes in myocardial function can occur, where ejection fraction decreases due to modification of left ventricle (LV) function.8,9 This will reduce contractility function, increasing the risk of acute pulmonary edema and acute heart failure.\n\n\nConclusion\n\nSmoking is one of the most common habits in people all over the world. Many adverse effects may occur because of smoking. One of them is ACS which STEMI is one of the diseases included. One of many therapies that may be done to reflow the blood’s obstruction. Percutaneous coronary intervention (PCI) is one of them, and now it is claimed as the most advantageous to reperfuse the coronary artery. Failure of this therapy may happen, and the no-reflow phenomenon is the most common. Smoking may induce the no-reflow phenomenon and may lead to heart failure, increasing the risk of cardiogenic shock.\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\nOral informed consent for publication of their clinical details and/or clinical images was obtained from the patient. Oral rather than written consent was obtained because of the patient’s condition and education level of the family, and was approved by the ethical review board of West Nusa Tenggara Province hospital.",
"appendix": "References\n\nNotara V, Panagiotakos DB, Kouroupi S, et al.: Smoking determines the 10-year (2004-2014) prognosis in patients with Acute Coronary Syndrome: The GREECS observational study. Tob. Induc. Dis. 2015; 13(1): 38–39. PubMed Abstract | Publisher Full Text\n\nShemirani H, Tafti FD, Amirpour A: Comparison of no-reflow phenomenon after percutaneous coronary intervention for acute myocardial infarction between smokers and nonsmokers. J. Res. Med. Sci. 2014; 19(11): 1068–1073. PubMed Abstract\n\nMessner B, Bernhard D: Smoking and cardiovascular disease: Mechanisms of endothelial dysfunction and early atherogenesis. Arterioscler. Thromb. Vasc. Biol. 2014; 34(3): 509–515. Publisher Full Text\n\nBarua RS, Ambrose JA: Mechanisms of coronary thrombosis in cigarette smoke exposure. Arterioscler. Thromb. Vasc. Biol. 2013; 33(7): 1460–1467. PubMed Abstract | Publisher Full Text\n\nGuelker JE, Blockhaus C, Jansen R, et al.: Influence of smoking habits on acute outcome of revascularization of chronic total occlusion. Turk. Kardiyol. Dern. Ars. 2018; 46(6): 439–445. PubMed Abstract | Publisher Full Text\n\nFajar JK, Heriansyah T, Rohman MS: The predictors of no reflow phenomenon after percutaneous coronary intervention in patients with ST elevation myocardial infarction: A meta-analysis. Indian Heart J. 2018; 70: S406–S418. PubMed Abstract | Publisher Full Text\n\nKarimianpour A, Maran A: Advances in Coronary No-Reflow Phenomenon—a Contemporary Review. Curr. Atheroscler. Rep. 2018; 20(9): 44. PubMed Abstract | Publisher Full Text\n\nPantea-Roșan LR, Pantea VA, Bungau S, et al.: No-reflow after ppci—a predictor of short-term outcomes in stemi patients. J. Clin. Med. 2020; 9(9): 1–16.\n\nGalasso G, Schiekofer S, D’Anna C, et al.: No-reflow phenomenon: Pathophysiology, diagnosis, prevention, and treatment. a review of the current literature and future perspectives. Angiology. 2014; 65(3): 180–189. Publisher Full Text\n\nBouleti C, Mewton N, Germain S: The no-reflow phenomenon: State of the art. Arch. Cardiovasc. Dis. 2015; 108(12): 661–674. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "148891",
"date": "13 Sep 2022",
"name": "Cut Aryfa Andra",
"expertise": [
"Reviewer Expertise Cardiovascular intervention"
],
"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 case report is interesting and deserves to be studied, where it is said that many chemicals in cigarettes can cause lipid oxidation so that plaque deposits. The article explained that there can be a no-reflow phenomenon (NRP), where there is no return of coronary flow after percutaneous coronary intervention, in patients with smoking habits. Smoking can cause hypercoagulable states, decreased endothelial function, decreased oxygen supply, increased inflammation, platelet aggregation, thromboxane production, plasma thickening, and the amount of fibrinogen, thereby increasing the risk of plaque formation.\nThe author adds insight to us that smoking is one of the important risk factors for heart attacks, both in the case of no backflow or no reflow phenomena. We need to realize that both in developing and developed countries, there are still many people who smoke and we should provide education about the dangers of smoking.\nIn addition, some words may need to be revised.\nIn the introduction session, there was a typo in the lack of \"Electrocradiogram\"\n\nIn case report section, “…..He is a high school teacher with no same medical or familial, or psychosocial history before….” It appears that before may be unnecessary in this sentence, consider removing it.\n\nIn case report section , ‘’…Blood examination was measured, and there was no abnormality..’’ It seems that you should add finding after the word abnormality\n\nIn case report section , “..Coronary angiography was then done and confirmed that there was total occlusion in left anterior descending artery…” It appears that then may be unnecessary in this sentence, consider removing it.\n\nIn case report description, please add the picture of angiography result\n\nIn the case description “…After two days hospitalization, the patient developed to cardiogenic shock and lead to acute decompensated heart failure. It seem that you are missing preposition “the “. It’s considered to add the before hospitalization..”\n\nIn the case description “Two days after PCI, the patient complained of chest pain again. It seem that better to use recurrent chest pain”\n\nIn Discussion , last sentence”….This will reduce contractility function, increasing the risk of acute pulmonary edema and acute heart failure…” It seem that you are missing preposition “the “. It’s considered to add the before contractility.\n\nIn the discussion session, data from Shemirani et al., showed that the incidence of the no-reflow phenomenon was not significantly different between smokers and non-smokers, it could be revised by adding \"s\" to be non smokers.\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": []
},
{
"id": "153430",
"date": "08 Nov 2022",
"name": "Mario Enrico Canonico",
"expertise": [
"Reviewer Expertise Clinical Cardiology"
],
"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 show the manuscript entitled \"Case Report: Smoking as the risk factor of persistent STEMI after primary percutaneous coronary intervention: how it could be happen?\"\nSome comments:\nHow did the Authors assessed the no-reflow? Echocardiography is not useful for this purpose. Moreover, echocardiography can't make coronary artery disease diagnosis\n\nNo-reflow depends by several factors (e.g. platelet reactivity, comorbidities)\n\nWhy didn't the Authors perform a second coronary angiography? In order to assess acute complications as stent thrombosis.\n\nImages quality on EKG and Echo should be improved\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": []
}
] | 1
|
https://f1000research.com/articles/11-801
|
https://f1000research.com/articles/12-1484/v1
|
20 Nov 23
|
{
"type": "Research Article",
"title": "Digital teaching competence of higher education professors: self-perception study in an Ecuadorian university",
"authors": [
"Jenniffer Sobeida Moreira-Choez",
"Jimmy Manuel Zambrano-Acosta",
"Alexander López-Padrón",
"Jimmy Manuel Zambrano-Acosta",
"Alexander López-Padrón"
],
"abstract": "Background Teaching professionalization aimed at the digital transformation of educational scenarios and training processes for students in contemporary higher education requires the mastery of digital competence by the teaching staff. The objectives of the study were to analyze the self-perceived level of digital teaching competence (DTC) of the faculty of the Technical University of Manabí (UTM), Ecuador, and to establish the relationship between age, sex, and academic profile variables with digital teaching competence.\n\nMethods A quantitative methodological approach was adopted to develop a descriptive-correlational field study with a non-experimental design. The participants were 277 professors, selected through non-probabilistic and voluntary sampling, who completed the DigCompEdu Check-In questionnaire sent by e-mail.\n\nResults The data showed that the integrator and expert categories obtained high levels in all competencies. There is also a difference in the pedagogy variable by the interaction of sex and academic profile.\n\nConclusions It is concluded that the competences self-perceived by the professors are within the intermediate categories such as integrator and expert. Likewise, the age, sex, and academic profile variables differ in the digital pedagogy level, which produces an inconsistent relationship, with the exception of the variable evaluates and provides feedback, where it was significant.",
"keywords": [
"Digital competences",
"university professors",
"self perception",
"educational modality",
"information and Communication Technologies"
],
"content": "Introduction\n\nTechnology plays a crucial role in contemporary and future society, with significant implications for the educational field.1 The rapid pace of technological change has introduced profound challenges in teaching and learning.2 As a result, educators must recognize the necessity of self-directed professional development to enhance their expertise, including achieving an adequate level of digital literacy. This proficiency is essential for success across various dimensions of education and training.3\n\nAs key institutions responsible for fostering the development of professional competence, universities must possess qualified resources, both in terms of materials and human capital, to prepare well-rounded professionals.4–6 These professionals should be equipped with problem-solving skills, critical thinking abilities, and the right attitudinal disposition necessary to navigate the complexities of the digital age. However, despite the acknowledged importance of technology in education, there are significant gaps in research regarding how educators can effectively select and utilize technological tools within their teaching practices.\n\nTherefore, it becomes crucial for educators to develop proficiency in selecting appropriate technological tools and seamlessly integrating them into their instructional approaches. By doing so, they can plan and implement activities that foster learning environments conducive to student success.7 Unfortunately, there is a dearth of comprehensive research that explores how educators can fully leverage the potential of technology to enhance teaching and learning in the classroom.\n\nHence, this study aims to address these research gaps by examining educators' self-perception of their digital competences and their capacity to effectively select and utilize technological tools in their teaching practice. By gaining a better understanding of the challenges and needs faced by educators in this context, more effective training and support strategies can be developed to foster their professional development and enhance the quality of education in the digital age.\n\nThe findings of this study will have significant implications for educational institutions, policymakers, and educators themselves. Understanding educators' self-perception of their digital competences will shed light on their level of confidence and awareness regarding the use of technology in education. Furthermore, identifying the challenges they face in selecting and utilizing technological tools will provide valuable insights into the barriers they encounter in integrating technology effectively into their teaching practice.\n\nBased on these insights, tailored training programs can be developed to address the specific needs of educators, helping them acquire the necessary skills and knowledge to make informed decisions about technology integration. Additionally, the study will contribute to the development of guidelines and best practices for selecting and utilizing technological tools, benefiting both novice and experienced educators in their pedagogical endeavors.\n\nUltimately, the aim of this study is to improve the educational landscape by equipping educators with the tools and resources they need to navigate the ever-evolving digital terrain. By enhancing educators' digital competences and supporting their professional growth, the quality of education can be elevated, ensuring that students receive an education that prepares them for the challenges and opportunities of the digital age.\n\nDigital Teaching Competence (DTC) encompasses the knowledge, skills, and abilities required for effectively utilizing digital media.8 It enables individuals to achieve various life goals through the use of technology. Consequently, the design, implementation, and execution of training initiatives for incorporating digital tools and pedagogical approaches in academic practice are considered essential professional requirements.9\n\nFurthermore, the integration of technology in education effectively depends on various factors related to the environment.10 Therefore, it is crucial to acknowledge that DTC is a constantly evolving competence, parallel to the advancements in technology itself.11 It is evident that DTC promotes learning when applied with interactive pedagogical tools, enhancing the efficiency of the theoretical model.12\n\nWithin the framework of DTC, different dimensions are identified, categorized by models and standards established for its evaluation. The International Society for Technology in Education (ISTE) and the National Institute of Educational Technologies and Teacher Education (INTEF) propose five areas of digital competences for educators: information and information literacy, communication and collaboration, digital content creation, security, and problem-solving.13–15 These competencies are further divided into three levels: Basic, Intermediate, and Advanced, which are classified as A1, A2, B1, B2, C1, and C2 based on the individual's level of proficiency.\n\nIt is worth noting that several studies conducted on DTC in the context of higher education reveal its transformative nature. The integration of digitalization in education presents two key tasks for professors: the development of their own digital skills and the cultivation of skills necessary for students to adapt to the digital world16,17\n\nMoreover, it is essential to recognize that digital competencies play a significant role in achieving the Sustainable Development Goals outlined in the United Nations' 2030 agenda. These competencies represent a set of skills that contribute to the pursuit of equality and social improvement.\n\nConsidering the aforementioned factors, it is important to highlight the assumed definitions of Digital Teaching Competence (DTC). It is described as the ability to develop operational capabilities with the support of various technological devices, enabling access to the internet for information retrieval. Consequently, the apprehension of DTC has emerged as a flexible and critical approach, adapting its use to the realities of the social environment, and evolving, expanding, and deepening its integration in all areas, including education.17\n\nBased on the literature reviewed, it is evident that the importance of DTC is recognized through the development of frameworks and self-evaluation instruments aimed at measuring the level of DTC appropriation by professors and educational managers, along with the integration and utilization of information and communication technology (ICT).18,19 These frameworks and instruments align closely with educational policies and strategies proposed by Digitally Competent Educational Organizations, the European Framework for Digital Competence of Educators (DigCompEdu), the Mentoring Technology-Enhanced Pedagogy (MENTEP) project, and the United Nations Educational, Scientific and Cultural Organization (UNESCO).10\n\nOn the other hand, UNESCO's Mentoring Technology-Enhanced Pedagogy Project (MENTEP) aims to incorporate the technical model of information and communication technologies (ICT) into the pedagogical environment to enhance teaching through technology, specifically through Massive Open Online Courses (MOOCs). This project also offers professors the opportunity to self-assess their digital competences and identify their areas of improvement through the TET-SAT standardized test20\n\nAdditionally, the European Framework for Digital Competence of Educators (DigCompEdu) provides a reference for the development of digital competences at all educational levels. Based on a scientific foundation, DigCompEdu helps identify needs, deepen knowledge, expand skills, and promote professional development. It encompasses six competence areas: professional commitment, digital resources, teaching and learning, assessment and feedback, student empowerment, and development of students' digital competence.21,22\n\nWithin the broad spectrum of instruments available to measure digital technological competencies (DTC), the selection of an appropriate tool is a critical process. This choice should not be based solely on criteria of robustness and reliability but must also consider its relevance to the specific research context. For this research, the DigCompEdu Check-in instrument was chosen. Originally designed by Ghomi and Redecker, this tool has undergone a rigorous translation and adaptation process led by Cabero-Almenara and Palacios-Rodríguez, thereby ensuring its applicability and relevance across various cultural and linguistic contexts.\n\nWhat makes the DigCompEdu Check-in even more special, in addition to its meticulously standardized structure, is its open-access nature. This feature makes it a highly versatile tool that can be used in various studies and research contexts. It facilitates the assessment of a wide range of competencies and skills associated with the digital realm in education. Given its inherent robustness, reliability, and validity, it stands as a paramount choice in the research field, especially for studies centered on the deep understanding and analysis of educational digital competencies.\n\nThe decision to use this questionnaire is not based only on its outstanding intrinsic features but also on the significant recognition and trust it has accumulated within the scientific community.19,23 Its open-access status not only underscores its adaptability but also highlights its contribution and value in the academic world, allowing for greater collaboration and consistency in research surrounding digital competencies.\n\nIn the current educational model, young people are immersed and actively engaged in the digital world. Therefore, ICTs serve as essential tools for their social and academic development. However, the use of technological devices, the internet, and social networks also exposes them to new challenges, dangers, threats, and electronic risks, such as harassment, identity theft, and scams.\n\nFurthermore, the coronavirus disease 2019 (COVID-19) pandemic and the rapid transition to online learning worldwide have brought about significant transformations in teaching practices.24 This situation raises questions about the preparedness of professionals for such changes and the digital capabilities of participants in the digitization process.\n\nGiven these considerations, it becomes necessary for professors to continuously update their knowledge regarding educational methods, pedagogical techniques, and technological advancements. Technology is recognized as one of the most influential tools across various domains, including social, educational, and professional spheres. Therefore, the teaching staff at the Technical University of Manabí (UTM) should actively engage in technological innovations, considering their direct and indirect involvement and commitment to society based on current educational realities.\n\nIt is noteworthy that while technologies continue to advance rapidly, professors often lag behind in keeping pace. This misalignment suggests that their actions may not always meet the demands of the globalized world. To address this, professors should actively seek ongoing training and development opportunities to cultivate broader capabilities. They should embrace new and motivating tools that facilitate different and innovative ways of learning for their students.25 This involves employing teaching and learning methods and techniques that promote meaningful learning experiences.\n\nBased on the aforementioned considerations, this study aims to achieve two objectives. Firstly, to analyze the self-perceived level of digital competence among professors at UTM in Ecuador. Secondly, to establish the relationship between age, sex, and academic profile variables and the digital competence of professors. The study adopts a quantitative approach, employing surveys to collect data based on sex, age, and level of academic training variables.\n\n\nMethods\n\nTo explore the proposed objectives, a descriptive correlational study was designed, supported by a quantitative approach and a non-experimental design structure. The methodological choice was neither random nor incidental but was deliberately aligned with the overall goals of the research. The focus was on delving into the essential core of the studied phenomenon and the intricate relationships between predetermined variables.26 It is noteworthy that the strategy adopted is based on a strictly observational model, excluding any form of direct intervention or manipulation of the subject matter.\n\nWithin this framework, the following key elements are established:\n\n• Critical phases in the research process were meticulously identified. These stages include the recruitment period for participants scheduled for the year 2022, specific moments for exposing the study subjects to the variables of interest, carefully structured follow-up phases, and predetermined timeframes for the empirical data collection.\n\n• Proactive measures were taken to identify and mitigate potential sources of bias. For this, statistical methods such as random probability sampling and weighted tests were applied. These techniques were specifically adapted to the peculiarities and demands of the research with the aim of preserving objectivity and impartiality in the results.\n\n• The selection of the number of participants was based on advanced statistical algorithms. These considered both the analytical power and the estimated effect size of the variables in question. This dual approach not only maximized the capability to detect significant interactions or impacts but also minimized the risks of erroneous inferences. In the event of missing data, consolidated statistical methodologies are applied. Initially, the nature and extent of the missing data were assessed. Subsequently, data imputation techniques were opted for, or alternatively, analyses based on complete records were carried out. This procedure ensured the integrity and reliability of the data and its subsequent interpretations.\n\nIn accordance with the ethical imperatives governing academic research, a meticulous procedure for obtaining informed consent from participants was diligently executed prior to the administration of the research instrument. This is a critical facet in the realm of scientific inquiry, designed to ensure that participants are not only fully aware of the study's overarching aim and methodology but also of any prospective risks and benefits that may arise from their involvement.\n\nTo facilitate a comprehensive understanding of the study's parameters, informed consent documents were articulated in a lucid and accessible language, deliberately avoiding any complex technical terminology that could potentially obfuscate participants' comprehension of the study's scope and implications. This approach was adopted to reinforce the principle of voluntariness, emphasizing that participants were free to either abstain from or withdraw from the study at any point, without suffering any negative repercussions.\n\nAt the same time, strict protocols were established to safeguard the confidentiality and privacy of the data collected from the participants. Detailed explanations were provided regarding the mechanisms to protect the identity and personal data of the participants. Once any pending questions or concerns were addressed, participants were invited to officially register their consent. This was achieved through the signing of the informed consent document, before proceeding to administer the questionnaire through Google Forms.\n\nThe authorization for the execution of the current research was granted by the Institutional Ethics Committee, and the funding was facilitated by the Honorable University Council of the Technical University of Manabí. This support was institutionalized through the issuance of resolution RHCU.UTM-No.259-SO-10-2022, dated January 10, 2022, thus preceding the data collection phase.\n\nIn the context of the current investigation, the designated study population consists of the full faculty body of the Technical University of Manabí, totaling 992 academic professionals (N=992). Through the deployment of a non-probabilistic, purposive, and voluntary sampling methodology, the research determined an estimated sample size of approximately 277 faculty members (n≈277). Unlike methods employing probabilistic sampling, this specific strategy did not aim to produce a representative subset of the population but focused on obtaining a more incidental selection of participants.\n\nTo facilitate the recruitment process, the researchers disseminated an electronic invitation to all faculty members at the Technical University of Manabí. This invitation included an embedded questionnaire tailored to the research objectives. Regarding the eligibility criteria, the researchers favored an expansive and inclusive approach, allowing participation from all faculty members, without imposing limitations based on departmental or disciplinary affiliations.\n\nIt is critical to acknowledge that due to the voluntary and non-probabilistic characteristics of the chosen sampling approach, the sample may not offer an accurate representation of the entire faculty demographic. However, the research team assessed this method as the most suitable, given the resource constraints and specialized objectives guiding the study.\n\nIn an effort to obtain a comprehensive range of perspectives relating to digital competencies, the study included faculty members from various academic departments and diverse professional backgrounds. This consideration of multidimensional diversity gains particular relevance in the context of the research objectives, which aim to explore the dimensions of digital competencies within the unique academic environment of the Technical University of Manabí.\n\nTo conclude, it is essential to underscore that electronic mail served as the primary channel for the distribution of research questionnaires. This approach not only streamlined the data collection process but also provided an effective mechanism for preserving participant anonymity and convenience. These attributes conformed to the ethical and logistical requisites integral to the research design.\n\nIn the current research, the DigCompEdu Check-in instrument was used for data collection.41 This tool was initially developed by Ghomi and Redecker in 2019 and disseminated by the Joint Research Center. To meticulously adapt it to the Spanish context, Cabero-Almenara and Palacios-Rodríguez23 stepped in, ensuring its availability in open access and under a Creative Commons Recognition License for its use in various research endeavors. The instrument is structured as a survey and encompasses 22 items, which are categorized into six competency domains: Professional Commitment, Digital Resources, Digital Pedagogy, Assessment and Feedback, Empowering Students, and Facilitating Students' Digital Competence. A five-interval Likert scale was utilized to evaluate the responses, offering five answer options for each item. Additionally, demographic variables such as gender and age were collected.\n\nThe coding of the items was accomplished using an alphanumeric combination of two or three letters. In the case of competence domains denoted by two letters, the first letter signifies the particular domain. For example, the letter “C” is associated with the “Professional Commitment” domain, while the subsequent letters, ranging from ‘A’ to ‘D,’ identify specific items within that domain. This coding pattern is replicated in other domains, using, for instance, the letter “R” for the “Digital Resources” domain and “P” for “Digital Pedagogy.”\n\nAs for the administration method, the survey was distributed via Google Forms. This digital tool not only facilitated efficiency in data distribution and collection but also ensured the anonymity of the participants. In this way, ethical guidelines were met, and logistical considerations were addressed, thus ensuring the appropriate implementation of the research design.\n\nFollowing the data collection via surveys, an inferential analysis was conducted with the aim of elucidating the self-perception that educators have regarding their digital competencies. To eliminate ambiguities in the categorization of these competencies, a secondary alphabetical character was assigned to each group when two groups shared the same initial letter. Thus, “Evaluation and Feedback” was coded as “EfV,” while “Empowerment” was labeled as “EP.”\n\nDuring the variable construction phase, a composite index (CALIF) was calculated for each participant. This was achieved by summing the corresponding values of the responses for the items linked to each competency domain. The composite index ranged from 0 to 88 points. Once these scores were obtained, the individuals' competency levels were categorized according to the grading scheme outlined in Table 1.\n\nThe processing and analysis of the data were carried out using the SPSS-21 software, a tool that ensures solidity and accuracy in the achieved results. Despite the advantages offered by this licensed software, it is prudent to consider open-source alternatives, such as JASP, which is not only free but also features a graphical interface for statistical analysis.\n\nFor each area of competence, a variable was generated with the sum of the scores of the items that constituted the area of competence, and together with each numerical variable, a categorical variable was conceived as suggested by,23 as specified below:\n\nCOMMITMENT. Based on the responses of the competence areas “Professional Commitment”, it took values from 0 to 16 points, its categorical variable was named COMP_C.\n\nDIGPEDAGOGY. Based on the responses of the competence areas “Digital pedagogy”, which took values from 0 to 16 points, its categorical variable was named PEDAGO_C.\n\nDIGRESOURCES. Based on the responses of the competence area “Digital Resources”, which took values from 0 to 12 points, its categorical variable was named RECDIGC.\n\nEMPOWER. Based on the responses of the competence area “Empowering Students”, which took values from 0 to 12 points, its categorical variable was labeled EMPODERAC.\n\nEVALUATESANDPRO. Based on the responses of the competence area “Evaluation and Provides feedback”, which took values from 0 to 12 points, its categorical variable was labelled EVALUAYRC.\n\nFACILITATESCO. Based on the competence area, “Facilitating Students' Digital Competence”, which took values from 0 to 20 points, its categorical variable was named FACILITACOC.\n\nThe validation of the instrument was carried out through the reliability test through Cronbach's Alpha, where it could be determined in a general and internal way, applying for this purpose the SPSS-21 statistical software, as shown in Table 2. Likewise, 22 items were used giving a value of 0.949, indicating a high level of reliability. Table 3 includes the result of the behavior of each item to the reliability, which showed the importance of all the items within the instrument.\n\n\nResults\n\nThis section presents the findings of this study.40 First, a reliability test was conducted using Cronbach's alpha coefficient to assess the internal consistency of the survey items (see Table 3). Cronbach's alpha is a widely used measure to evaluate the reliability of a scale or questionnaire. It indicates the extent to which the items in the instrument measure the same underlying construct.\n\nTable 3 displays the results of the reliability test. The coefficient value obtained provides an indication of the overall internal consistency of the instrument. A higher value suggests a greater degree of reliability, indicating that the items in the instrument measure the construct consistently. Conversely, a lower value may indicate inconsistency in the measurements.\n\nThe reliability test was conducted using statistical software, such as SPSS-21, which allows for the calculation of Cronbach's alpha coefficient. The test involved analyzing the responses to the 22 items included in the instrument. Reliability statistics provide valuable information about the robustness and stability of the instrument used in the study. By evaluating the internal consistency of the items, researchers can ensure that the instrument is reliable and yields consistent results.\n\nTable 3 delineates the outcomes of Cronbach’s alpha reliability assessment for a range of competencies, segmented under various domains pertinent to professional endeavors. These domains encompass Professional Engagement, Digital Resources, Digital Pedagogy, Evaluation and Feedback, Empowering Students, and Facilitating Students' Digital Competence.\n\nUpon meticulous examination, it becomes evident that all competencies under investigation exhibit remarkable reliability. This assertion is substantiated by Cronbach’s alpha values, which span between 0.946 and 0.949. Such values, particularly when surpassing the 0.7 threshold, are conventionally deemed to be emblematic of substantial internal consistency.\n\nTransitioning our focus to the scale mean and variance in the event of item deletion offers a profound understanding of the potential fluctuations in these metrics should a specific competency be excluded. On average, the scale mean gravitates around 52.5 for the various competencies, insinuating a harmonious scale. In parallel, the scale variances, which oscillate primarily between the mid-120s and 130, display marginal variations among the competencies, reinforcing the notion that there are no pronounced disparities among them.\n\nMoreover, an analysis of the correlations unveils a discernible linear association between individual competencies and the corrected total score. This score represents the cumulative value of all items, excluding the item currently under consideration. Notably, the correlation coefficients span from 0.500, evident in the Organizational Communication within the Professional Engagement domain, to 0.751 observed in Active Student Participation under Empowering Students. These consistently positive correlations imply that an uptick in scores for individual competencies is frequently associated with a surge in the overall score.\n\nLastly, by evaluating the column that depicts Cronbach's alpha in scenarios where an item has been excised, one gleans pivotal insights regarding the influence of individual competencies on the overarching reliability of the measurement tool. An attenuated value in this column, in contrast with the intrinsic Cronbach's alpha, intimates a potential decrement in reliability upon the removal of the said competency. Nonetheless, the relatively minute distinctions underscore that any singular competency's omission would unlikely induce a substantial shift in the tool's internal consistency.\n\nSubsequently, a descriptive analysis was conducted to examine the participants' responses, considering the five intervals established by the Likert scale (Table 4). Descriptive analysis involves summarizing and interpreting the collected data to provide a comprehensive understanding of the participants' evaluations.\n\nThe results presented in Table 4 highlight the distribution of participants across different competence levels in each area. In the Professional Commitment competence, the highest levels are observed among experts and integrators, accounting for 38.99% and 36.46% respectively. On the other hand, the pioneer level has the lowest representation with only 0.72%, followed by the explorer, leader, and novice levels, which account for 16.97%, 3.61%, and 3.25% respectively.\n\nTurning to the Recognizes, Evaluates and Empowers competency, Table 4 reveals that the integrator category holds the highest percentage with 39.35%, followed by the expert category with 35.38%. The explorer category represents 13.00%, while the novice, leader, and pioneer categories account for 2.53%, 9.03%, and 0.72% respectively.\n\nIn the Digital Pedagogy competence, the integrator category stands out with the highest representation at 40.07%, closely followed by the expert category at 39.71%. The explorer category accounts for 9.39%, while the leader, pioneer, and novice categories have percentages of 7.94%, 2.53%, and 0.36% respectively.\n\nIn the Evaluates and Provides Feedback competence, 46.21% of the surveyed professors position themselves in the integrator category, while 32.13% identify themselves as experts. Additionally, 9.03% consider themselves explorers, 7.58% as leaders, 3.68% as pioneers, and 1.44% as novices.\n\nRegarding the Empowers Students competence, the results indicate that 42.60% of the respondents have an expert level, while 32.85% are classified as integrators. The leader, explorer, pioneer, and novice categories represent 9.03%, 8.30%, 4.69%, and 2.53% respectively.\n\nExamining the Facilitates Competences competence, the majority of professors, 48.74%, are categorized as integrators, followed by experts at 36.82%. The explorer, leader, pioneer, and novice categories account for 5.05%, 3.61%, 3.25%, and 2.53% respectively.\n\nThese results provide insights into the distribution of participants across competence levels, highlighting the variations in self-perceived digital competences among the surveyed professors. Understanding these distributions is crucial for designing targeted interventions and support strategies to enhance digital competences and promote professional development in the educational context.\n\nTable 5 presents the analysis of variance, which examines the sources of variation, the degrees of freedom, and the sum of squares for each numerical variable investigated. Analysis of variance (ANOVA) is a statistical technique used to determine the significance of differences between groups or categories.\n\nWhen examining the sources of variation such as sex, academic profile, and age, as well as their interactions, significant differences are observed in the “pedagogy variable” due to the interaction effect between sex and academic profile. This suggests that the relationship between sex and academic profile influences the variability in pedagogical competence.\n\nFurthermore, the relationship between academic profile and age accounts for approximately 31.892% of the variability in professional commitment. This indicates that the combination of academic profile and age significantly contributes to variations in the level of professional commitment.\n\nSimilarly, the confluence of sex, academic profile, and age has a notable impact, accounting for 11.755% of the variability in digital resources. This suggests that the interaction among these factors plays a significant role in determining the level of digital resource competency.\n\nTable 6 provides a summary of the Chi-Square test results, which examines the independence of each factor against all categorical variables in each competence area. The “Pvalue” column indicates the significance of each test, with a significance criterion of α=0.05. If the test is not significant, it suggests that the variables are independent. However, for example, in the case of the “Evaluates and provides feedback” variable, a significant relationship with sex is found.\n\nRegarding age, independence is observed in the “Evaluates and provides feedback” and “Empowers students” variables, suggesting that age does not significantly affect these competences. However, in the other variables, a significant relationship is found between age and the rest of the competences, indicating a non-independent effect of age on those variables.\n\nFor the academic profile, independence is found in relation to age, except in the “Empowers students” variable. This implies that the academic profile has a significant relationship with age in most competences, except in the case of empowering students.\n\nThese findings highlight the complex interplay of factors and their interactions in influencing the variations observed in different competence areas. Understanding these relationships is essential for tailoring educational interventions and designing targeted strategies to enhance specific competences based on sex, academic profile, age, and their combinations.\n\nWithin the possibilities of multidimensional scaling with the application of the multivariate technique, stress is presented as a measure of goodness of fit, whose indicator was ‘weak to poor’ with a value of 0.1828, which is reflected in the graph represented by a regression in Figure 1, where the degree of coupling of the data can be observed. However, in the Stress value, it was visualized that there was closeness between the items of the ‘Empowers’, ‘Evaluates’, ‘Facilitates Digital Competence’ competence areas. Therefore, the items of these areas of competence formed two compact groups of items, sharing items between one group and the other, but indicating that in general these items formed a construct.\n\nSource: Data provided by respondents, processed with SPSS-21 statistical software.\n\nAs it can be observed, it was verified that Professional Commitment and Digital Resources were left out of this group. In this way, it was observed that the most dispersed items were those of Professional Commitment. On the other hand, only “Reflective Practice” and “Professional Collaboration” were relatively close to each other, but very far from “Digital Training” and “Organizational Communication”. Likewise, the “Digital Resources” items were found to be close to each other. Consequently, it could be considered that the items of these two areas formed another construct.\n\nNext, a two-stage factor analysis was performed.\n\nThe results of the factor analysis with the maximum likelihood method and the “Oblimin” oblique rotation method option showed a KMO value of 0.961 and Bartlett's test of sphericity was significant, indicating that the application of the factor analysis was adequate.\n\nThe lower part of Table 7 shows the characteristic values of the first two factors, and it was observed that with the first two factors a cumulative explained variance of 56.58% was obtained which was considered acceptable, suggesting a two-factor model. The first factor was made up of the competences that were mainly aimed at the achievement of empowerment by students of digital tools to apply them to the teaching-learning process.\n\nThe second factor generated a construct that described the professors’ personal attitudes toward their training and use of digital tools. That is, construct one referred to the entire pedagogical structure, and construct two to the professors’ personal training and use of it.\n\nSimilarly, Table 7 presents the factors and the loadings of each of the items within the factors. Thus, the rotation analysis made it possible to achieve what the literature suggests as a good result in factor analysis, in other words, that each factor is made up of variables with high values and some variables with values close to zero, and that each variable belongs to only one of the factors.\n\nTherefore, variables with small values in the factors were omitted to avoid duplicities, taking as a criterion for the elimination of values lower than 0.35. For this reason, only two items could not be fully discriminated against, which were Professional Collaboration and Evaluation Strategies. However, Professional Collaboration was more important in factor 1, while Evaluation Strategies was more important in factor 2. Finally, it was observed that the item Digital Training was not part of any of the factors to obtain the scores.\n\nIt is clear that through the assisted clustering analysis, three groups were identified. These are shown in Figure 2.\n\nSource: Data provided by respondents, processed with SPSS-21 statistical software.\n\nIn this analysis, it was found that the grouping of participants was strongly influenced by factor 1, which pertained to the pedagogical aspect. Group 1 comprised professors who exhibited higher ratings on construct 1, indicating a strong emphasis on pedagogy. Group 2 represented an intermediate category, characterized by a balance between the two constructs. On the other hand, Group 3 consisted of professors whose ratings on construct 2 prevailed.\n\nThese groupings suggest that participants varied in their emphasis on different aspects of teaching and learning. Group 1 highlighted a strong focus on pedagogical approaches, while Group 3 demonstrated a greater emphasis on the second construct, which may be related to other dimensions or competences.\n\nUnderstanding these groupings provides insights into the diverse perspectives and preferences of educators in relation to teaching practices and competences. It enables researchers and educators to identify specific areas where professional development and support can be targeted to enhance teaching effectiveness and promote a well-rounded approach to education.\n\nTo describe more precisely the constitution of the groups, the means corresponding to each of the variables that calculated the score in each area of competence were generated, the results of which are shown in Table 8.\n\nTo provide a more detailed description of the group composition, the means for each variable that contributed to the calculation of the score in each competence area were computed. The results of this analysis are presented in Table 8.\n\nTable 8 displays the mean values for each variable within each competence area. These means offer a comprehensive understanding of the specific aspects or dimensions that contribute to the overall score in each competence area. By examining the means, researchers can identify the relative strengths and weaknesses of the participants in different areas of competence.\n\nAnalyzing the means enables a more nuanced interpretation of the group composition and allows for a deeper exploration of the participants' competences. It provides valuable insights into the specific areas where educators excel or require further development.\n\nBy considering these mean values, researchers and educators can design targeted interventions and strategies to enhance specific competences and address any areas of improvement identified. This information contributes to the overall goal of fostering professional growth and enhancing the quality of teaching and learning experiences.\n\n\nDiscussion\n\nUpon examining the results, it is evident that the Integrator and Expert categories consistently present higher percentages in various competencies, such as PROFESSIONAL COMMITMENT, RECOGNIZE, EVALUATE AND EMPOWER, DIGITAL PEDAGOGY, EVALUATE AND PROVIDE FEEDBACK, EMPOWER STUDENTS, and FACILITATE COMPETENCIES. This indicates that teachers who perceive themselves as integrators and experts demonstrate a higher level of Digital Teaching Competence compared to explorers and novices. Additionally, leaders and pioneers, albeit fewer in number, show greater knowledge and abilities in these competencies.\n\nThese findings align with studies conducted by Espino-Díaz et al.,27 and Hämäläinen et al.28 which similarly highlight a pattern of behavior in competencies leaning towards a low to medium competence level. The study by Peled29 also supports this idea, suggesting that there is a positive correlation between teachers' self-perception as experts or integrators and their level of Digital Teaching Competence.\n\nIn terms of demographic factors, Table 5 shows that sex and academic profile exhibit the highest values on the digital pedagogy variable. This suggests that, regardless of sex, educational teaching techniques are applied without gender bias, contributing to the development of Digital Teaching Competence. Furthermore, the lower values imply that sex is not a significant factor in acquiring commitments or fulfilling professional responsibilities in teaching.\n\nThese findings align with the discoveries of Guillén-Gámez et al.,30 who emphasize the limited differences between sex and age in terms of self-perception of digital competencies. This corroborates that sex does not have a significant impact on learning and teaching abilities related to the use and management of digital tools. It also suggests the need to plan and implement strategies for integrating digital competencies into teacher training programs.\n\nRegarding age, the percentages indicate that it is not perceived as a limitation for acquiring or fulfilling commitments related to the appropriation of digital resources. This finding aligns with Suárez and Colmenero,31 where no statistically significant association was found between age and competence level, indicating that there are no significant differences among different age groups. This result is also backed by the study of Gudmundsdottir and Hatlevik,32 suggesting that digital competence is not determined by age, but rather by attitude and training.\n\nTable 6 examines the relationship between factors, including sex, age, and academic profile. It indicates that sex is independent of the variables, except for “Evaluate and provide feedback,” suggesting that sex influences the search for possibilities to identify and verify knowledge. Also, the “Evaluate and provide feedback” and “Empower students” variables show the lowest values, indicating that age does not determine processes involving communication with students.\n\nRegarding the academic profile, the “Empower students” variable obtains the highest score, indicating that teachers strive to provide students with the necessary support and information to guide their development. Although some teachers possess basic or intermediate digital skills, it is essential that they empower their students through adequate training. This aligns with the study conducted by Colás-Bravo et al.,33 emphasizing the need for teachers to contribute to developing critical, reflective, creative, and innovative thinking in students through proper training. Aidoo et al.34 study supports this idea, suggesting that teachers need to have a deeper understanding of how to use digital tools to empower students and foster their autonomous learning.\n\nThe correlation analysis presented in Figure 1 highlights the interrelationship between items related to competencies such as “Empower”, “Evaluate”, and “Facilitate Digital Competence.” This suggests that as teachers set out to empower students, they contribute their own competencies to improve students' skills, thus demonstrating their commitment to professional performance and teaching praxis.\n\nHowever, it is important to note that Professional Commitment and Digital Resources were not included in this construct, indicating that not all teachers share the same attitude towards student training, possibly due to resource limitations. Another construct formed by “Digital Training” and “Organizational Communication” suggests the existence of divided positions regarding empowerment practices.\n\nFindings from List35 support this idea, as they indicate that the management of digital identities in the educational context, specifically in the dimensions of communication and collaboration, is limited among teachers. This suggests that there is a need for further development of digital competencies among educators. Similarly, the study of Benitt et al.36 concludes that teachers need more comprehensive training in digital competencies to effectively utilize technologies in teaching.\n\nTable 7 provides an analysis of the factors, indicating that Professional Collaboration competencies, which contribute to the application of strategies in adapting virtual environments, have greater relevance in educational processes. Also, Evaluation Strategies is identified as a significant factor in determining the extent of learning and organizing improvements. This aligns with the study conducted by López-Belmonte et al.,37 emphasizing the importance of promoting teachers' participation in training programs focused on developing digital competence and using emerging methodologies. These programs aim to adapt teaching practices to the new techno-pedagogical paradigms of a digitized society.\n\nFigure 2 identifies three distinct groups of teachers. The first group (G1) emphasizes the importance of grades in pedagogical processes, while the second group (G2) lacks a clear definition. The third group (G3) expresses limited contributions to the topic. These findings are consistent with the conclusions drawn by Gil-Jaurena and Domínguez,22 who recommend incorporating more profound educational technology content into training programs to improve educational quality and enable appropriate teaching praxis for the digital age. Moreover, the findings of the study by Rapanta et al38 support this recommendation, suggesting that a better understanding of educational technology can help teachers adapt their practices to students' needs and expectations in the digital environment.\n\nFinally, Table 8 presents the mean values and standard deviations of the formed groups. It reveals that Group 1 (G1) shows the lowest proportional effect on the “DIG RESOURCES” variable, indicating that without adequate digital resources, teachers face limitations in providing quality education. On the other hand, Group 1 (G1) shows the highest weighted average on the “FACILITATESCO” variable, suggesting that the ability to facilitate required competencies largely depends on the interaction between teachers and their students. In Group 3 (G3), the “DIGRESOURCES” variable receives the lowest scale, underlining the importance of having digital resources to promote skills for effective use of digital environments. These findings align with the study conducted by Pozo-Sánchez et al.,39 which associates higher digital competence scores with dimensions related to information and communication literacy and collaboration.\n\nThe study provides a comprehensive view of how teachers perceive themselves in terms of digital competence and how this perception relates to demographic variables such as gender, age, and academic profile. However, certain limitations and ambiguous areas suggest the need for further and more detailed research in the future.\n\n\nConclusions\n\nThe findings of the descriptive analysis shed light on the self-perception of digital teaching competence among UTM professors, revealing an overall trend towards the integrator and expert categories. Notably, competences such as “Facilitates Competences,” “Evaluates and Provides Feedback,” and “Digital Pedagogy” were frequently highlighted.\n\nFurthermore, the study identified significant differences in the relationship between age, sex, and academic profile and professors' digital competence, particularly in the “Digital Pedagogy” domain. This indicates an inconsistent relationship between sex and academic profile, with most variables exhibiting independence, except for the “Evaluates and Provides Feedback” variable, which showed significance.\n\nRegarding age, a relationship was found in the “Evaluates and Provides Feedback” and “Empower Students” variables, while independence was observed for the remaining variables. The study acknowledges certain limitations, primarily the lack of random sampling, which hindered the creation of a more balanced and homogeneous sample. Consequently, the generalizability of the findings may be limited.\n\nFuture research directions should focus on designing training programs tailored to address the specific digital teaching competence needs of professors in order to effectively tackle the challenges posed by the digital era. These programs should incorporate formative and procedural aspects that allow participants to actively produce and implement their learning, emphasizing practical application to meet real needs.",
"appendix": "Data availability\n\nFigshare: Data- Digital teaching competence of higher education professors.xlsx. https://doi.org/10.6084/m9.figshare.24084393. 40\n\nThe project contains the following underlying data:\n\n- Data- Digital teaching competence of higher education professors.xlsx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nFigshare: European Framework for Digital Competence of Teachers (DigComEdu) questionnaire. https://doi.org/10.6084/m9.figshare.24224065. 41\n\nThe project contains the following extended data:\n\n- QUESTIONNAIRE (DigComEdu).xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nGarzón-Artacho E, Sola-Martínez T, Romero-Rodríguez JM, et al.: Teachers’ perceptions of digital competence at the lifelong learning stage. Heliyon. 2021; 7: e07513. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPinargote-Macías EI, Vega Intriago JO, Moreira Choez JS, et al.: Competencias del docente universitario en tiempos de pandemia. Revista Venezolana de Gerencia. 2022; 27: 347–359. Publisher Full Text\n\nTejedor S, Cervi L, Pérez-Escoda A, et al.: Digital Literacy and Higher Education during COVID-19 Lockdown: Spain, Italy, and Ecuador. Publications. 2020; 8: 48. Publisher Full Text\n\nDomingo-Coscollola M, Bosco-Paniagua A, Carrasco-Segovia S, et al.: Fomentando la competencia digital docente en la universidad: Percepción de estudiantes y docentes. Revista de Investigación Educativa. 2020; 38: 167–182. Publisher Full Text\n\nHämäläinen R, et al.: Understanding teaching professionals’ digital competence: What do PIAAC and TALIS reveal about technology-related skills, attitudes, and knowledge? Comput. Hum. Behav. 2021; 117: 106672. 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Publisher Full Text\n\nPeled Y: Pre-service teacher’s self-perception of digital literacy: The case of Israel. Educ Inf Technol (Dordr). 2021; 26: 2879–2896. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGuillén-Gámez FD, Mayorga-Fernández MJ, Bravo-Agapito J, et al.: Analysis of Teachers’ Pedagogical Digital Competence: Identification of Factors Predicting Their Acquisition. Technol. Knowl. Learn. 2021; 26: 481–498. Publisher Full Text\n\nSuárez AS, Colmenero MR: The challenge of incorporating digital skills in the classroom: perceptions and attitudes of Spanish Salesian teachers. Int. Stud. Cathol. Educ. 2021; 1–16. Publisher Full Text\n\nGudmundsdottir GB, Hatlevik OE: Newly qualified teachers’ professional digital competence: implications for teacher education. Eur. J. Teach. Educ. 2018; 41: 214–231. Publisher Full Text\n\nColás-Bravo P, Conde-Jiménez J, El Reyes-de-Cózar S : desarrollo de la competencia digital docente desde un enfoque sociocultural. Comunicar. 2019; 27: 21–32.\n\nAidoo B, Macdonald MA, Vesterinen V-M, et al.: Transforming Teaching with ICT Using the Flipped Classroom Approach: Dealing with COVID-19 Pandemic. Educ Sci (Basel). 2022; 12: 421. Publisher Full Text\n\nList A: Defining digital literacy development: An examination of pre-service teachers’ beliefs. Comput. Educ. 2019; 138: 146–158. Publisher Full Text\n\nBenitt N, Schmidt T, Legutke MK: Teacher Learning and Technology-Enhanced Teacher Education.2019; 1171–1193. Publisher Full Text\n\nLópez-Belmonte J, Moreno-Guerrero AJ, Pozo-Sánchez S, et al.: Efecto de la competencia digital docente en el uso del blended learning en formación profesional. Investigación Bibliotecológica: archivonomía, bibliotecología e información. 2020; 34: 187–205. Publisher Full Text\n\nRapanta C, Botturi L, Goodyear P, et al.: Balancing Technology, Pedagogy and the New Normal: Post-pandemic Challenges for Higher Education. Postdigital Science and Education. 2021; 3: 715–742. Publisher Full Text\n\nPozo-Sánchez S, López-Belmonte J, Rodríguez-García A-M, et al.: Teachers’ digital competence in using and analytically managing information in flipped learning (Competencia digital docente para el uso y gestión analítica informacional del aprendizaje invertido). Cult. Educ. 2020; 32: 213–241. Publisher Full Text\n\nMoreira-Choez JS, Zambrano Acosta JM, López Padrón A: Data- Digital teaching competence of higher education professors.xlsx. [Data]. Figshare. 2023. Publisher Full Text\n\nMoreira Choez JS, Zambrano Acosta JM, López Padrón A: European Framework for Digital Competence of Teachers (DigComEdu) questionnaire. [Data]. Figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "246734",
"date": "29 Mar 2024",
"name": "Dirgha Raj Joshi",
"expertise": [
"Reviewer Expertise Educational technology",
"Applied Mathematics",
"Quantitative Research",
"SEM",
"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\nTitle: Digital teaching competence of higher education professors: self-perception study in an Ecuadorian university Abstract: Results in the abstract is just like conclusion hence it must contain some statistical values of core findings. Keywords: can add one additional keyword Background/Introduction The research question should be added in the background section. There several paragraphs with out reference in the background section hence such paragraphs should be modified or remove. The theoretical explanation is good however missing literature review section hence some additional empirical literature is needed to add in the background section. Why researcher used each case capital like as “COMMITMENT” in the manuscript. Methodology Several unnecessary information is mentioned under methodology section it will be better to organize it in the following manners as Research design 1-2 sentence Population sample and sampling technique -3-5 sentences Research instrument 3-5 sentences Variable information and validity and reliability of the instrument- one paragraph Data collection and data cleaning process- one paragraph Data analysis technique- one paragraph. Sample size is appropriate based on population however how it was calculated not clear hence should mentioned with reference. There are some gaps like why researcher used chi-square test instead of regression analysis. Results\nResearcher made two factors in Table 7 however there is no any further analysis based on these factors. The items were dived into six categories in Table 3-Table 5 however the data demands only two categories hence further analysis based on gender and other variables on two factors is needed. Discussion Discussion is appropriately explained however additional discussion and results are needed based on the results of two factors (Table 7). Conclusion Limitation, implication, and recommendation should be added in separate section. Citation and references Need to check as per authors guideline. Language Language should be improved.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "224295",
"date": "12 Sep 2024",
"name": "Alexa Angelica Senior-Naveda",
"expertise": [
"Reviewer Expertise Educación",
"Gestión educativa",
"Calidad educativa",
"Desarrollo sostenible",
"Capital Social",
"Gobernanza",
"Redes."
],
"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\nAs a final concept, the evaluator considers that the inconsistencies present between the objectives set out in the introduction and the objectives that appear inserted in the theoretical framework must be resolved. To resolve this disagreement, it is suggested to correct the objectives of the introduction and delete from the theoretical framework section the same. Regarding the theoretical framework, the need to cite scientific articles that constitute empirical references for the application of the objectives of the 2030 agenda for sustainable development is highlighted in terms of the search for equality and social improvement based on use of technology in the Ecuadorian educational context The reviewer considers it necessary to correct the procedures declared as probabilistic in the methods section because in the sample estimation and sampling section the researchers declare that they carried out non-probabilistic sampling, which makes the methodological component inconsistent. Regarding the statistical parametric Cronbach's Alpha, this is not a result on the behavior of the variables, but rather a statistical requirement of the validity and reliability of the measurement instrument, on the discriminatory power of the items and the degree in which which the variance of each of the items measures the discriminatory power with respect to each indicator, as well as the variance of the entire instrument, which provides a measure of the variation of the variables studied. Therefore, these calculations should be part of a subsection of the methods section. It is also necessary to theoretically and scientifically support the adaptation of the data collection instrument to the Ecuadorian or similar context, since Cabero-Almenara and Palacios-Rodríguez adapted it to the European context, specifically to the Spanish context, which has cultural, demographic, socio-educational and economic conditions different from those of Ecuador. Once the previous corrections have been carried out both in the objectives declared in the introduction, as well as the objections in the methods, data analysis and results section; The article can be considered to have a coherent statistical analysis. It is highlighted that the data is available. Conclusions are inferred from the results. The article presents an important topic in the socio-educational area and of great interest today.\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": []
}
] | 1
|
https://f1000research.com/articles/12-1484
|
https://f1000research.com/articles/13-1298/v1
|
29 Oct 24
|
{
"type": "Policy Brief",
"title": "Water pollution: causes, impacts and current efforts to address the issues of water pollution along river Meizimera-kihihi, Kanugu District,Uganda.",
"authors": [
"Abraham Ariho",
"Lucy Aja",
"Tukur Muhammad",
"Lubega Mohammad",
"Abraham Ariho",
"Tukur Muhammad",
"Lubega Mohammad"
],
"abstract": "Pollution refers to the addition of harmful substances to that level where they cause an effect on the environment, it has three major categories such as water, soil, and air pollution but this report is on water pollution. It occurs when harmful substances contaminate water bodies such as, groundwater, rivers, lakes, and oceans rendering them unfavorable for various purposes for example drinking, recreation, and support to aquatic life. Globally, over 80% of wastewater worldwide is discharged into the water bodies without adequate treatment. In Africa, lack of clean water and sanitation is a significant challenge in many countries, affecting approximately 319 million people. Thus, water pollution is one of the types of pollution that has been threatening the lives of living organisms. Implementing effective policies and strategies can have a profound impact on the environment and local communities. By reducing pollution levels and improving water quality, we can create a healthier environment and decrease the incidence of waterborne diseases, leading to improved health and well-being for residents. The research on water pollution in the River Meizimera Kihihi has important implications for future research, policy and governance, human health, the environment, and communities and society. In conclusion, effective policies can foster community involvement, raise awareness, and promote collective action to address water pollution. By achieving clean water and sanitation (SDG 6), we can contribute to the broader sustainable development goals. This research has important ramifications for future research, policy and governance, human health, the environment, communities, and society. This study investigated the problems of water pollution, its causes, its impact, and the current effort to address the issues along the river of Meizimera-kihihi, Kanugu district, Uganda. Recommendations were made, which included encouraging the adoption of sustainable agricultural practices, industrial processes, and waste management strategies to minimize pollution.",
"keywords": [
"Water Pollution",
"Causes of Water Pollution",
"Impacts of Water Pollution",
"River Meizimera-Kihihi"
],
"content": "Introduction\n\nThe term pollution refers to the addition of harmful substances to the level at which they affect the environment. Pollution is the introduction of any substance such as solid, liquid, or gas into the environment in an amount that can hurt the environment, wildlife, human health, and well-being. Three major categories of pollution are affected by the type of environment being affected. These factors include water, air, and land pollution. Harmful substances are called pollutants and they include nitrogenous wastes, domestic wastes, metal, plastics, and many others. Some pollutants are biodegradable whereas others are non-biodegradable. Biodegradable substances can be broken down by natural processes, which are made from organic materials from animals, plants, or microorganisms such as food waste, cotton, and paper, while any natural processes cannot break down non-biodegradable substances which are made from synthetic materials such as bottles, glass, plastic bags and aluminum cans (Manasa & Mehta, 2020; Sahoo & Goswami, 2024).\n\nTherefore this study aims to analyze the causes, impacts, and current efforts to address water pollution in Meizimera-Kihihi, Kanungu, District, Uganda. Kihihi is the second–largest city in the Kanungu district and is located in Western Uganda. The district has many rivers and streams including Kiruruma, Birara, Nchwera, Ishasha, and Meizimera. The people of Kihihi use the river Meizimera for various purposes such as fishing, irrigation, washing, bathing, drinking water sources, religious and cultural purposes, brick making and sand mining, recreation, and livestock watering. The dependence on rivers for various purposes increases the risks of water pollution which has many harmful effects on human health, the economy, and the environment. A description of the pollution of the river and its consequences are elaborated below:\n\nGlobally, over 80% of wastewater worldwide is discharged into water bodies without adequate treatment (UN report, 2020), and in Asia, only one-third of wastewater is treated before being discharged (Asian Development Bank, 2023). In Africa, the lack of clean water and sanitation is a significant challenge in many countries, affecting approximately 319 million people worldwide. In East Africa, eutrophication and algal blooms of L. Victoria pose significant environmental and public health risks. In Uganda, studies show that only 30% of the population has access to improved sanitation facilities hence there is a widespread contamination of water sources with fecal matter and plastic especially in urban centers (WHO, 2019; UNEP, 2020; Manasa & Mehta, 2020; Sahoo & Goswami, 2024).\n\nWater pollution occurs when harmful substances contaminate fresh and marine water bodies such as, groundwater, rivers, lakes, and oceans rendering them unfavorable for various purposes such as drinking, recreation, and support to aquatic life. Over 80% of human-generated sewage is dumped untreated into rivers and oceans, causing pollution that causes over 50 diseases. In addition, poor water quality is linked to 80% of diseases globally (Lin et al., 2022). According to Taylor et al. (2008) and Sahoo and Goswami (2024) progressive increases in industrialization, urbanization, and agricultural practices are the leading causes of water pollution. This alleviates the most common problem of eutrophication where inland waters and rivers are polluted with nitrogen and phosphorus runoff from fertilizers and the discharge of sewage and effluents.\n\nAlthough efforts have been made to reduce water pollution, this phenomenon remains a challenge in most parts of the world. The dependence on rivers for various purposes increases the risks of water pollution which has many harmful effects on human health, the economy, and the environment. Therefore, this report aims to explore the causes, and impacts of water pollution, assess current efforts to address this problem, and provide recommendations for future action. The economic activity and terrain of the area have an impact on the river Meizimera as observed and recorded here below: All Observations were made during the study.\n\nThe issues of water pollution affecting the river of Meizimera-kihihi range from, the decrease in water clarity as a result of pollutants which reduces the transparency of water making it difficult for aquatic plants to photosynthesize. Changes in river flow due to pollution can lead to flooding and erosion. Excess nutrients from the runoff of agricultural activities and sewages lead to eutrophication causing algal blooms and the depletion of oxygen levels in the river. Contaminated water poses many health challenges such as typhoid, cholera, and diarrhea to local communities that depend as a source on the river as a source of water, and there has been a decline in fish populations in the river which affects the livelihoods of fishermen.\n\nThese are the environmental areas of River Meizimera, Kihihi, Uganda. The appearance of the river changes with the seasons, there is an increase in the flow of water during the rainy season and a decrease during the dry season. The river has been affected by pollution and human activities which affect water quality and the aesthetic value in some areas of the river (Researcher’s observations, 2024).\n\nThis makes the area a busy place with approximately 1000 people including workers visiting the place daily. Some of this waste is dumped in the river (Researcher’s observations, 2024).\n\nThe area is urban, just at the base of Kihihi town, in the valley down the town hill. The water from the washing bay may contain oils, chemicals, and other detergents that can have harmful effects on aquatic life in the river and contaminate the water. Water from the bay also makes the river less appealing for tourism and recreational purposes (Researcher’s observations, 2024).\n\nThese can easily be eroded into the water. These have a devastating effect on the environment, aquatic life, and also human health (Researcher’s observations, 2024).\n\nPeople who stay along the river wash their clothes and household utensils and direct their sewage into the water body. Farming occurs along the river bank and some soil is eroded into the river. The river is seen to be fertile at the old stage point of the river with a slightly green appearance indicating the growth of algae and other vegetation (Researcher’s observations, 2024).\n\nWater plant growth in rivers leads to oxygen depletion, nutrient competition, and the obstruction of recreational activities (Researcher’s observations, 2024).\n\nImplementing effective policies and strategies can have a profound impact on the environment and local communities. By reducing pollution levels and improving water quality, we can create a healthier environment and decrease the incidence of waterborne diseases (Levy et al., 2018), leading to improved health and well-being for residents. Moreover, clean water can support various economic activities such as fisheries and tourism, generating income and stimulating local economic growth. Successful policies can also protect biodiversity, preserve ecosystem balance, and maintain the natural beauty of the river (Arthington et al., 2010).\n\nEffective policies can foster community involvement, raise awareness, and promote collective action to address water pollution (Bisung, 2021). Additionally, they can ensure efficient use of water resources, reducing waste and promoting sustainable practices. By achieving clean water and sanitation (SDG 6), we can contribute to the broader sustainable development goals. Successful policies can be replicated and scaled up to address water pollution in other districts, supporting national and global efforts to protect water resources and ensure a sustainable future for all.\n\nThe research on water pollution in the River Meizimera Kihihi has important ramifications for future research, policy and governance, human health, the environment, and communities and society. It emphasizes the necessity of more stringent regulations, stepped-up enforcement, community involvement, and ongoing monitoring to address the causes and effects of pollution and guarantee sustainable development. Significant implications of the study include increased risk of waterborne illnesses and long-term health effects; environmental degradation, including harm to aquatic life and ecosystems; economic impacts, including loss of income and livelihoods; community and social impacts, including improved quality of life; and future research directions, emphasizing the need for community engagement, ongoing monitoring, and evidence-based solutions to address the causes and effects of pollution and support economic growth.\n\nTherefore the following strategies to address pollution in this and the world at large are as follows. The bi-products from factories; the coffee and \\rice husks are sold to other industries where they can be made useful. In this case, two factory owners said these husks are taken to the Hima cement factory and also to the Mbarara Yoghurt industry where they are used as a source of heat/fuel since they are good at soring heat/fire for a long period. This is because they are good insulators. The coffee husks are bought by many farmers who use them as a source of organic manure in gardens. So they are taken by those who bring coffee to the factory for other agricultural purposes and chicken feeds hence reducing pollution of the area. There are strict orders for factory owners to collect their husks in a controlled space and avoid dumping them everywhere. The factories have shifted from using petrol and diesel as fuel to using electricity which has reduced other forms of pollution.\n\nGovernments enact laws and regulations to control pollution, such as the Clean Water Act in the United States and the European Water Framework Directive in Europe, In Rwanda, plastic bags were banned from the market. NGOs and governmental organizations conduct awareness campaigns to educate the public about the importance of water conservation and pollution prevention. Advances in wastewater treatment technologies for example UV disinfection, pollution monitoring systems, and eco-friendly practices help mitigate pollution and improve water quality before discharge. And International agreements and initiatives, such as the United Nations Sustainable Development Goals and the Paris Agreement, foster cooperation among nations to combat water pollution on a global scale (Javed et al., 2022; Zahoor & Mushtaq, 2023).\n\n\nConclusion\n\nWater pollution remains a critical environmental and public health challenge, requiring concerted efforts at local, national, and global levels to address its root causes and mitigate its impacts. By implementing comprehensive regulatory measures, promoting sustainable practices, investing in infrastructure, raising awareness, and fostering innovation, we can work towards ensuring clean and safe water for present and future generations of the people of Meizimera, Kihihi, Uganda.\n\nTo address water pollution in River Meizimera –Kihihi, we recommend adopting sustainable agricultural practices, industrial processes, and waste management strategies to minimize water pollution. There should be enforcement mechanisms and penalties for polluters to ensure compliance with environmental regulations. Also, there should be awareness to educate the public about the importance of water conservation, pollution prevention, and responsible consumption to foster behavioral changes and community engagement. Investment in upgrading and expanding water treatment facilities, sewage systems, and stormwater management infrastructure will help to prevent pollution and safeguard water resources and finally allocate resources to research institutions and initiatives focused on developing innovative solutions for water pollution control and management.\n\nA consent form was signed by the LC chairperson of Kihihi Town Ward so that the research could be carried out in the community. Proof of the signed form by the LC is attached to this manuscript. The following steps were implemented to protect the rights of participants whose images appeared during observation. All participants were thoroughly informed about the goals and advantages of the study and the participant gave their consent verbally with no written documents. The reason for verbal consent was that most of the participants in this research couldn’t write. Faces depicted in the image were de-identified, and participant identities were kept private. There was no ethical approval but there was a consent form that was signed by the chairperson. Neither the environment nor the volunteers were harmed by the research. The community intended to gain from the research by having problems with water pollution and sustainable habits. Lastly, the study was conducted impartially, guaranteeing advantages for all parties involved.",
"appendix": "Data availability\n\nNo data associated with the article.\n\n\nReferences\n\nArthington HA, Naiman RJ, Clain ME, et al.: Preserving the biodiversity and ecological services of rivers: New Challenges and Research Opportunities. Freshw. Biol. 2010; 55(1): 1–16. Publisher Full Text\n\nAsian Development Bank: Global report on sanitation and wastewater management in cities and human settlements.UN-HABITAT; 2023.\n\nBisung E: Community-based collective action for safe water in rural Sub-Saharan Africa. Water Security. 2021; 13: 100088. Publisher Full Text Reference Source\n\nJaved MA, Hanif U, Rashid F, et al.: Enhancing functionalities in nanocomposites for effective dye Removal from wastewater: Isothermal, Kinetic, and Thermodynamic Aspects. Water. 2022; 14(17): 2600. Publisher Full Text\n\nLevy K, Smith SM, Carlton EJ: Climate change impacts on waterborne diseases. moving toward designing interventions. Curr. Environ. Health. Rep. 2018, Jun; 5 (2): 272–282. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLin L, Yang H, Xu X: Effect of Water pollution on human, health and disease heterogeneity: A Review. Front. Environ. Sci. 2022; 10. Publisher Full Text\n\nManasa RL, Mehta A: Wastewater: sources of pollutants and its remediation. Environ. Biotechnol. 2020; 45: 197–219. Publisher Full Text\n\nSahoo SK, Goswami SS: A theoretical framework for assessing the economic and environmental impact of water pollution: A detailed study on sustainable development of India.2024; 4(1): 23–34. Publisher Full Text\n\nTaylor DJ, Green NPO, Stout GW: Biological science 1 & 2. 3rd ed.New York, NY: Cambridge University Press; 2008.\n\nUnited Nations Environment Programme (UNEP): World water quality assessment.2020. Reference Source\n\nUN report: UN World Water development report 2020, water and climate change.UN-Water Publications; 2020.\n\nWorld Health Organization (WHO): Water pollution and health.2019. Reference Source\n\nZahoor I, Mushtaq A: Water pollution from agricultural activities: a critical global Review. Int. J. Chem. Biochem. Sci. 2023."
}
|
[
{
"id": "349693",
"date": "30 Dec 2024",
"name": "Kalmia E Kniel",
"expertise": [
"Reviewer Expertise Microbiology",
"Food Safety",
"Food Security",
"Wastewater"
],
"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 difficult to provide a detailed review given the lack of line numbers. This paper tackles a subject that is likely important to the area and worthwhile of study. While the information is useful and the paper is informative, there is a lack of references throughout the manuscript. These references should be added to provide background and evidence of the additional information.\n\nSpecific comments include: The capitalization in the last line of the next to last paragraph on page 3 of the pdf file should be checked.\nThe statements on page 3 regarding issues of pollution in the river are greatly lacking references.\nAs the authors state, seasonal changes are important to this river. During what season is Figure 1? This should be included. Also what are the precipitation changes that occur seasonally? How do these impact runoff from urban areas?\nIs there an image that could replace the current Figure 2 where the faces are not showing and therefore do not need to be blacked out. It seems there could be a section on explaining the wastes coming from the different processing factories.\nArrows could be added to Figure 4 to show where the leaking oils and byproducts are.\nSpecifically what types of recreation would the river support if it were not as polluted? How might this impact the economy or have other impacts?\nThe observation of green bottles in Figures 5 and 6 is apparent. Are these always present? Was this unusual? Are these green glass bottles or plastic? Are they unique to this area? Is there recycling or trash collection in the area.\nAre there infrastructure changes that could impact pollution? What is the likelihood of these infrastructure changes, or perhaps challenges that are associated with necessary implementation?\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": [
{
"c_id": "13219",
"date": "27 Jan 2025",
"name": "Lucy Aja",
"role": "Author Response",
"response": "Thanks for the report. We are also going to improve the paper. All issues raised are for the betterment of the paper."
}
]
},
{
"id": "339695",
"date": "16 Jan 2025",
"name": "Balamurugan Paneerselvam",
"expertise": [
"Reviewer Expertise Groundwater pollution"
],
"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\nAdd more details about background of the present study. while fixing the policy for environmental safety, discuss more about the negative impacts in present study area Water pollution, source of contamination, major contaminants, and its impact on human health should be discussed, Please make a note to discuss this details Did you find any health impact on human body? or genetic or other changes in any living organisms? Should be discuss in detail\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? No\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": "13220",
"date": "27 Jan 2025",
"name": "Lucy Aja",
"role": "Author Response",
"response": "Thanks for the report, all issue raised will be improved on."
}
]
}
] | 1
|
https://f1000research.com/articles/13-1298
|
https://f1000research.com/articles/13-1297/v1
|
29 Oct 24
|
{
"type": "Research Article",
"title": "Chest Wall Hydatid Disease: Surgical management and risk Factors for Recurrence and Mortality",
"authors": [
"Asma Saad",
"Imen Bouassida",
"Houda Rouis",
"Hedia Bellali",
"Amina Abdelkbir",
"Mahdi Abdennadher",
"Yoldez Houcine",
"Hamida Kwas",
"Hassen Makhlouf",
"Mondher Mestiri",
"Mondher Kooli",
"Sofiene Bouali",
"Jalel Kallel",
"Hazem Zribi",
"Adel Marghli",
"Imen Bouassida",
"Hedia Bellali",
"Amina Abdelkbir",
"Mahdi Abdennadher",
"Yoldez Houcine",
"Hamida Kwas",
"Hassen Makhlouf",
"Mondher Mestiri",
"Mondher Kooli",
"Sofiene Bouali",
"Jalel Kallel",
"Hazem Zribi",
"Adel Marghli"
],
"abstract": "Background Hydatidosis of the thoracic wall differs from other hydatid localizations in its pathophysiology, diagnostic, and therapeutic management. It is a little-studied entity. The objectives of our work were to describe its surgical management and to analyze the factors that may influence recurrence and mortality.\n\nMethods A retrospective, descriptive, longitudinal, and multicenter study on four university hospital surgical centers of Tunis, from January 1995 to December 2022 including operated hydatid cysts of the thoracic wall. Overall survival (OS) and cumulative recurrence rates were calculated. Univariate and multivariable Cox regression analyses were performed to identify recurrence and mortality risk factors.\n\nResults Forty-nine patients were included. The mean age was 41 ± 17 years [8-76]. The main presenting sign was thoracic parietal swelling (n=22). Chest ultrasound and CT scan showed multivesicular formation in 17 and 33 cases, respectively. Muscle involvement was in the intercostal (n=4), paravertebral (n=13), and pectoralis major (n=3) muscles. Bone involvement was vertebral (n=11), costal (n=12), costo-vertebral (n=21) and sternal (n=2). A posterolateral thoracotomy was performed (n=20). Surgical excision at various levels of the chest wall with spinal stabilization (n=15) was performed. Sixty-three percent of the patients received antiparasitic medical treatment. Recurrence occurred in 37% of cases. Four patients died from hydatidosis-related complications. Factors could be independently associated with recurrence such as male gender, and vertebral involvement. The presence of a visceral hydatid cyst located at a distance from the parietal lesion at the time of diagnosis and the occurrence of postoperative infectious complications could increase mortality.\n\nConclusions Chest wall hydatidosis represents a rare medical condition where surgery remains the preferred treatment modality. However, it carries a substantial burden of morbidity and mortality, influenced by various factors. Further large-scale studies are necessary to gain a deeper understanding of these factors and to optimize management strategies accordingly.",
"keywords": [
"E granulosus",
"Rib",
"Dorsal vertebra",
"Thoracic Surgery",
"Recurrence",
"Mortality"
],
"content": "Introduction\n\nHydatidosis or echinococcosis, also known as hydatid cyst or hydatid disease, is a cosmopolitan infectious prevalent in the Mediterranean basin, Australia, and South America. It is caused in humans, an accidental intermediate host, by the presence and development of the hydatid of a cestode of the genus “echinococcus granulosus” that resides in the small intestine of canids.1,2 Hydatid cysts represent a public health problem in endemic countries, particularly Tunisia, where the incidence is approximately 15.1 per 100,000 inhabitants,3 as well as in other countries where traditional livestock farming is still practiced, due to its frequency, severity, and socio-economic impact.\n\nThe location in the chest wall presents diagnostic, therapeutic, and prognostic problems. The long symptomatic silence of this disease (5-15 years) allows the lesions to spread rapidly before they are discovered,4 thus posing a differential diagnosis problem, explaining the diagnostic delay. Bone lesions are extensive with a very progressive evolution and can lead to definitive neurological complications.\n\nOur study aimed to describe chest wall surgical management and outcomes and identify possible associated recurrence and mortality risk factors.\n\n\nMethods\n\nEthics approval\n\nEthical approval was waived by the local Ethics Committee of Abderrahmane Mami University Hospital under the number 20/2024 in October 2024.\n\nPatient privacy and informed consent for publication\n\nWritten informed consent was obtained directly from the patients by the authors, regardless of their department of origin. Patients consistently provided consent before surgery as per standard hospital practice. Additionally, retrospective consent for study participation was acquired through telephone contact.\n\nAnonymity was respected during data treatment.\n\nConsent for publication of identifiable data\n\nNo consent for publication was required as the data had been anonymized. We confirm that such alterations have not distorted the scientific meaning.\n\nFollowing the Safe Harbor methods outlined by HIPAA, all radiologic images and patient photographs used in the study were thoroughly de-identified to ensure patient privacy. This process involved removing any direct identifiers such as patient names, dates of birth, medical record numbers, and facial features that could potentially lead to the re-identification of the individuals. Additionally, any metadata embedded within the images, such as timestamps or institution-specific details, were removed. This de-identification procedure was carefully followed to comply with the HIPAA guidelines and protect patient confidentiality throughout the study.\n\nPopulation source\n\nThe present study was retrospective, descriptive, and multicentric. It was over twenty-eight years: from January 1995 to December 2022.\n\nOur study was carried out in four university hospital centers in Tunis: the thoracic surgery department of Abderrahman Mami Hospital, Ariana, the neurosurgery department of the National Institute of Neurology in Tunis, the orthopedics department of the Mohamed-Kassab Institute of Orthopedics and the orthopedics department of Charles Nicolle Hospital in Tunis. We used the admissions database of these university hospital centers to collect records of patients operated on for hydatidosis of the chest wall (defined as hydatidosis affecting the bone (ribs, vertebrae, and sternum) and soft tissues). Fifty records were retrieved.\n\nInclusion criteria\n\nWe included all operated patients for hydatidosis of the chest wall, with complete records (observation, radiological findings, operative report, anatomopathological report, follow-up).\n\nNon-inclusion criteria\n\nWe did not include the patients operated on for suspected chest wall hydatidosis (CWH) and whose diagnosis was not retained after surgery or pathological examination, patients with confirmed CWH but who were not operated on (refusal, inoperable patients with high anesthetic risks).\n\nWe applied the inclusion and non-inclusion criteria and eliminated incomplete and unusable records. We retained forty-nine patients operated on for chest wall hydatidosis.\n\nA data collection form was drawn up in a standardized manner to collect all elements necessary to meet the objectives of our study.\n\nFor each patient, we collected information about epidemiological and anamnestic data: age, gender, geographical origin (rural or urban), the department of origin (thoracic surgery, orthopedics, or neurosurgery), notion of hydatid contagion, family history of hydatid cyst (HC), personal history of visceral hydatid cyst. We consider a history of multiple visceral hydatidosis and hydatid involvement of more than three viscera. We also examined clinical parameters such as the time to consultation (the time from the onset of symptomatology to the date of consultation), time to treatment (the time between the onset of the symptomatology and the date of surgery), the circumstances of discovery, including incidental findings, chest pain, swelling of the soft tissues of the thoracic wall presenting as a parietal tumefaction of the posterior thoracic or paravertebral wall, neurological symptoms, and respiratory involvement. Additionally, we evaluated physical examination parameters such as general examination, thoracic floor assessment, and neurological and abdominal examinations.\n\nThe radiological assessment included a chest X-ray, X-ray of the spine, coastal grid, thoracic, soft tissue, and abdominal ultrasound, CT-scan, Magnetic Resonance Imaging (MRI), and other radiological examinations such as medullary arteriography. Biological tests were carried out, including hydatid serology and a blood count to check for hypereosinophilia.\n\nWe specified the therapeutic management elements: anesthesia, surgical position, surgical approach, per-operative findings, and surgical procedure: which we have divided into three stages: surgical resection of part of the chest wall (including ribs, vertebrae, and/or muscles), surgical spinal stabilization: anterior by a bone marrow transplant or by osteosynthesis with a fixation material and conservative surgical procedure when the operation is performed only on the cystic lesion without ablating a part of the thoracic wall. We identified the used scolicidal solution (hydrogen peroxide, povidone-iodine, hypertonic saline), the protection of the operating field (use of soaked gauze in scolicidal solution to protect pleura and soft tissues for possible scolex dissemination), and we mentioned per-operative complications.\n\nWe recorded the duration of drainage, hospital stay, immediate postoperative course: simple or complicated, and late complications. Late course: was assessed by clinical examination (neurological by ASIA score to evaluate motor skills and sensitivity) and postoperative sequelae. During the follow-up period, every hydatid recurrence was recorded (time, treatment modalities, surgical treatment (approach, procedure, number of repeat surgeries, evolution after treatment of recurrences). Antiparasitic medical treatment was noted (molecule and length of treatment) and the pathological examination. We identified the mortality (frequency, causes, delay). We defined lost to follow-up patients as those who missed outpatient visits for over three consecutive years.\n\nThe data was analyzed using the IBM Statistical Package for the Social Sciences 25.0 software, accessed through the free 30-day trial available on IBM’s official website (https://www.ibm.com/products/spss-statistics#110). In our study, we proceeded to Calculate absolute and relative frequencies for categorical variables, means, medians (with minimum and maximum), and standard deviations for quantitative variables. For the quantitative variables, the distribution of the population was tested for normality. If the distribution was normal, the variables were described as mean, otherwise as median. We used the Kaplan-Meier survival curve by calculating the cumulative survival to study the survival relationships of the elected variables associated with recurrence and the elected variables associated with mortality. For the multivariate study, we used Cox regression to determine factors independently associated with recurrence and factors independently associated with mortality. All tests were two-sided, and a two-tailed probability value of 0.05 or less was considered statistically significant.\n\n\nResults\n\nDuring the study period, 49 patients were operated on for CWH. The mean age of our population was 41 ± 17 years [8-76 years] with a male predominance.\n\nAt the time of diagnosis, 15 patients had associated hydatid involvement at a distance, the others had exclusive parietal involvement. Bone involvement was vertebral (n=11), only costal (n=12), costovertebral (n=21) and sternal (n=2). There was soft tissue involvement adjacent to the costovertebral involvement in the intercostal and paraspinal muscles (n=13), as well as in the soft tissue of the supraclavicular fossa (n=2) with exclusive primary involvement of the pectoralis major muscle (n=1) and the paraspinal muscle (n=1).\n\nThe diagnosis of CWH was an incidental finding in three cases. The other patients were symptomatic with a combination of functional signs: thoracic pain (n=23), parietal swelling (n=22) (Figure 1A), neurological signs (n=22), and respiratory signs (n=7) (Table 1).\n\nA parietal swelling (arrowhead); B Chest radiograph, circle arrowed the cyst and its effect on ribs; C echography showing hydatid vesicles (arrowhead); D CT image: cystic lesion with cortical costal lysis (arrowhead).\n\nParaclinical investigations were carried out: chest X-ray was performed in 48 patients, i.e., 98% of cases, and mainly showed a parietal opacity in 19 cases (Figure 1B).\n\nUltrasound of the soft tissues was performed in 18 cases and the most frequent aspect was a hypoechogenic multivesicular formation (n=13) which guided the diagnosis (Figure 1C).\n\nAbdominal ultrasound was performed in 44 cases as part of the etiological and extension assessment of the hydatid disease and showed a hepatic HC (GHARBI type IV) in nine cases.\n\nThe thoracic CT scan was performed in 94% of cases (Table 1). Costal damage was in the posterior arch in 25 cases (51%). A tiered involvement of more than two ribs was observed in 43% of the cases, with a predominance of lesions at the Fourth to ninth rib level. The vertebral involvement was in the vertebral body in 21 cases and the intervertebral disc in two cases. In 16% of cases, the number of affected vertebrae was two or more. The most affected levels were D7-D9 (n=11) explained by the richness of the vascularization of this spine segment (Figure 1D, Figure 2).\n\nA-B Destruction of the spine and intracanal diffusion of hydatidosis (arrowhead and circle); C-D MRI showing a large multivesicular mass depending on the paravertebral muscle (arrowheads).\n\nThere was soft tissue involvement adjacent to the spinal involvement. The mean major axis of the lesion was 7.8 cm, with a size ranging from 3 to 30 cm in the major axis. Twenty-three patients had a lesion with a large diameter ranging from 5 to 10 cm.\n\nVertebro-medullary magnetic resonance imaging (MRI) was performed in 24 patients, i.e., 49% of cases (Table 1).\n\nAll patients were operated on. For costovertebral involvement, posterolateral thoracotomy was performed in 11 cases (61% of cases), a posterior approach in four cases (22% of cases), and a combined approach in 3 cases (17% of cases) (Figure 3).\n\nA Surgical position, arrow showing paravertebral swelling; B Flattening of hydatid abscesses; C Posterior approach revealing vertebral and intracanal hydatidosis; D Posterior spinal stabilization (osteosynthesis).\n\nThe surgical procedure was divided into three modalities: radical surgical removal, spinal stabilization, and conservative surgery without costovertebral resection (Table 2).\n\nA primordial time is the protection of the operating field by a scolicide solution. The main solutions were hypertonic saline and hydrogen peroxide (Figure 3).\n\nThe immediate postoperative course was simple in 94% of cases. The average length of hospitalization was 23.5 [5-55] days for isolated vertebral involvement, 19.8 [4-123] days for costovertebral involvement, 8.3 [1-35] days for isolated rib involvement, and three days for exclusive muscular involvement of hydatid disease. The difference between the average length of stay for the different conditions was not statistically significant (p=0.70).\n\nMedical treatment was prescribed to all our patients even for those who had a complete resection and was taken in 63% of cases. The antiparasitic molecule prescribed was albendazole in the form of a 400 mg tablet, per day in two doses, in the form of 21-day courses separated by one week. The antiparasitic medical treatment was mainly taken postoperatively in 14 cases and after the recurrence in 11 cases. The duration of the antiparasitic medical treatment was more than one year in 17 cases, i.e., 55% of the patients who had received medical treatment.\n\nPost-operative complications occurred in 24% of cases. There are three types of complications: neurological, infectious and decubitus. Neurological complications included paraplegia in two cases and paresis in six cases. The three main postoperative infectious complications were surgical wound infection (n=3) and pneumonia acquired by mechanical ventilation (n=3). Pressure sores were the main decubitus complication (n=4).\n\nThe postoperative evolutionary aspects were marked by a total disappearance of the initial symptomatology in 22 cases and a clinical aggravation in three cases. On the other hand, the different types of postoperative sequelae were mainly intercostal neuralgia in seven cases and paraplegia in five cases. Recurrence was a frequent complication that determines the prognosis of this rare disease and occurred in 18 cases (37%). The median time to recurrence was one year with extremes ranging from a month to 13 years. For recurrence, patients had medical and surgical treatment in most cases (n=14). For the different surgical revision procedures for recurrence, the main procedure was spinal decompression by laminectomy with partial corporectomy associated or not with spinal stabilization in eight cases. The mean number of repeat surgeries for recurrence was three times with extremes ranging from one to eleven times. Thus 61% of the patients who had a recurrence were reoperated on more than twice.\n\nOverall survival is estimated at 80% at five years. Seven patients (70% of those who died) had vertebral involvement. Patients with vertebral hydatid involvement had a 5-year survival of 71%.\n\nWe conducted an analytical study to determine the factors associated with recurrence and mortality. The univariate study looked at several parameters, epidemiological, radio-clinical, and parameters related to the management methods, represented in Tables 3-4.\n\nThe multi-varied study of these parameters identified the factors independently associated respectively with recurrence and mortality, which are shown in Table 5.\n\nMale gender, vertebral involvement, and antiparasitic medical treatment could be independently associated with recurrence. Associated distant hydatid cysts and postoperative infectious complications were the two factors associated with mortality.\n\n\nDiscussion\n\nCWH is an entity that encompasses the involvement of the soft tissues and the costovertebral and sternal bones.\n\nThe literature review revealed only case studies or articles about a few cases in the descriptive framework. Our work has added to the literature the experience of four university hospitals in a country where hydatidosis is endemic, through a descriptive and analytical study attempting to find factors associated with recurrence and factors associated with mortality that could jeopardize functional and vital prognosis.\n\nThe curative treatment for thoracic parietal echinococcosis is surgical.5,6 Results depend on the extent of the lesions, their location, and the presence of complications. It must be the subject of an exhaustive work-up and treated as a “malignant tumor” by a wide resection passing through healthy margins.7\n\nFor isolated rib involvement, the main surgical procedure was resection of the anterior or posterior arch or both. This resection was extended to more than two ribs in five cases.\n\nFor sternal involvement, the procedure was a manubriectomy. For isolated soft tissue involvement, resection of the hydatid cyst was combined with partial resection of the muscle involved.\n\nFor costovertebral lesions, a multidisciplinary surgical team comprising thoracic surgeons and orthopedic surgeons or neurosurgeons is required.\n\nFrom a technical point of view, the approach to the thoracic parietal lesion is often facilitated and guided by the ossifluent abscess, which is surgically traversed as far as the primary bony lesion, eliminating the hydatid vesicles in the process. Costovertebral lesions can be treated using a posterior approach alone, a posterolateral approach alone, or a combined approach (posterior and posterolateral). Each of these approaches has its advantages and indications, and a combined approach is recommended in most cases, particularly if a laminectomy has already been performed as part of a neurological emergency.8 Access to the vertebral bodies and ribs is difficult, and resection of hydatid material is often incomplete. The posterolateral approach has several advantages: it allows access to all the vertebral bodies of the dorsal spine and extensive excision of the spine, ribs, and muscles, with the possibility of reconstruction or osteosynthesis, and makes it possible to treat an associated pulmonary, pleural or mediastinal location. For costovertebral involvement, the data in the literature showed that most patients were operated on via the posterior approach.9,10 This was the only approach used in the series by Khazim9 and Bhavin.11 Although this approach offers the possibility of spinal decompression, excision of the hydatid process remains incomplete, with a high rate of mortality, neurological deficits, and fistulae. Other teams have used the posterior approach in addition to the posterolateral approach to search for one or more hydatid vesicles that have migrated into the spinal canal, far from the initial site of contamination, or for palliative treatment of multi-stage lesions.12 The combined posterior approach associated with PLT is recommended in most cases.9,10,13\n\nIn our study, posterolateral thoracotomy was performed most frequently. This was performed in 61% of cases of costovertebral involvement.\n\nThoracic parietal resection must be carried out with multidisciplinary management. At present, it is recommended to carry out as complete an excision as possible using a “carcinological” strategy.13–15\n\nSome hydatid lesions of the thoracic wall, spread over more than five vertebrae, are sometimes unresectable14 and require a conservative surgical procedure such as flattening of the hydatid abscesses, or spinal curettage, which was performed in two patients in our series, or even surgical abstention.14\n\nMedical treatment with albendazole is the only therapeutic alternative for inoperable patients, even though it may not cure or prevent recurrence. Its use as adjuvant therapy to surgery is generally necessary to prevent systemic dissemination during vesicular rupture and to reduce and delay recurrences. We have adopted this approach in our series. However, some teams believe that albendazole does not act on infested bone without a germ membrane.16\n\nRecurrence is considered a poor prognostic factor in chest wall hydatid (CWH) disease, particularly when it involves the vertebrae. Operative mortality of up to 14.4% has been reported in recurrences.17\n\nFor bone involvement, the results of surgery are far from curative and recurrence is the rule.12,17,18 In our series, recurrence was noted in 37% of cases. Recurrence surgery is associated with higher morbidity and mortality than initial surgery. However, most of these operations are only palliative.19\n\nSurgery may be repeated several times to completely eradicate echinococcosis but cysts involving the spine cannot be safely resected or excised in their entirety in most patients.17,19\n\nThere are cases of resistance that respond neither to surgery nor to medication. We report a case diagnosed as hydatidosis of the chest wall and treated with radiotherapy (RT) after medical and surgical therapy had failed. Ulger S et al report a case of hydatidosis of the sternum showing the value of RT for E. multilocularis as an alternative treatment20; however, based on the literature, we conclude that the effect of RT is not well known in this setting.\n\nHydatid involvement of the thoracic wall, and principally the spinal location, is associated with a non-negligible mortality rate of 3 to 46%.21 The overall mortality rate was 46% in the study by Zlitni,22 and 17% in that of Ezzaouia.23 Death is, in most cases, the consequence of infectious and decubitus complications.15,23,24 In our series, ten patients died. Patients with spinal hydatid involvement had an estimated survival of 71% at five years and 29% at 10 years. There was no statistically significant difference in survival between patients with and without vertebral hydatid disease (p=0.78). This can be explained by the small sample size of our series. Seven patients, i.e., 70% of those who died, had costovertebral hydatid lesions, and four died from complications of hydatid disease, mainly from decubitus complications (n=3). The other three patients were elderly, two of whom had associated pulmonary and secondary pleural hydatidosis.\n\nFew studies have examined survival factors, and none have explored risk factors for recurrence and mortality in this rare condition. In our multivariate analysis, we aimed to identify these factors, finding a recurrence rate of 37% and a mortality rate of 20% among our patients.\n\nAccording to the literature, thoracic parietal hydatidosis is more frequent in men.14,25 In our study, we also noted a male predominance. There were 31 men and 18 women, with a sex ratio of 1.7. This may be explained by the fact that males are more likely to associate with canids in rural areas. Gender may be a factor in recurrence (P=0.006), with recidivism six times greater for males (HR=6.032).\n\nBone echinococcosis can affect all bones but preferentially affects the spine.13,22 This is the most common location; 42% for Dévé2 and 44% for Zlitni. The site is mainly dorsal (56%).13,22 It is the most serious because of the neurological complications and the difficulties of surgical eradication. Although hydatidosis of the bone is a parasitic disease, its prognosis should be treated as if it were a malignant lesion. In our series, vertebral involvement is a factor associated with recurrence (P=0.025) and HR=10.2. Unlike visceral sites, the rigid structure of bone prevents the formation of adventitia, allowing parasites to spread through microvesicular infiltration of bone tissue. Exogenous vesiculation is characteristic of bone due to its rigidity, and results in the release of daughter vesicles from the mother vesicle, which explains the frequency of recurrences. There is no clear dividing line between healthy and pathological tissue, which is a major difficulty during surgical removal.22\n\nIn our series, patients who had taken antiparasitic medical treatment reattract the disease earlier than those who had not (p=0.006). This seems to be unwarranted however it can be justified by the common prescription of antihelminthic treatment for extensive hydatid lesions and the absence of a standardized protocol for this treatment. Certain factors influence the efficacy of benzimidazoles. Todorov et al. found that larger vesicle size, the presence of daughter vesicles, and, notably, bone involvement were associated with a poor response to medical treatment. This may be attributed to the small number of patients in our series.26\n\nWe studied several other factors that could be associated with recurrence and that were only significant in the univariate study. These included clinico-radiological factors such as the neurological deficit, vertebral compression, scalloping of the posterior vertebral wall, vertebral lysis, paravertebral extension, intracanal extension, and involvement of more than two vertebrae. Other factors related to management methods, such as the extent of surgical removal: laminectomy alone, complete costal resection, the occurrence of neurological complications and postoperative decubitus complications, and the occurrence of postoperative sequelae.\n\nThis may be explained by the heterogeneity of our sample, with a small enough number of patients to be able to generalize.\n\nThe mortality rate of patients followed for echinococcosis of the chest wall, essentially the dorsal spine is 3 to 14%.18,21,27\n\nHydatid involvement of the thoracic wall, and especially bone involvement, is rare, accounting for less than 2% of all hydatid cases, and is associated with a visceral cyst in 12 to 25% of cases. It is primary,2 rarely secondary, and occurs via the hematogenous route.21 In our series, patients with a visceral hydatid site at a distance from the parietal involvement at the time of diagnosis had a mortality rate 31 times higher, with a significant difference (p=0.005). This suggests that we should consider simultaneous treatment of visceral hydatid lesions if feasible.\n\nInfectious complications can cause high mortality. In our series, mortality was 40 times higher with the occurrence of infectious complications.\n\nWe studied several other factors that could be associated with mortality, such as the onset of chest pain, exclusive parietal involvement, which is a protective factor, costovertebral involvement, and costal resection. These were significant only in the univariate study. This may be explained by the small number of patients in our series, which makes it difficult to generalize.\n\nTo validate these conclusions and identify the factors contributing to recurrence and mortality, a prospective study with a larger sample size may be necessary. However, this is challenging due to the rarity of the disease.\n\n\nConclusion\n\nSurgery remains the treatment of choice for chest wall hydatidosis. If diagnosed early and treated promptly, CWH can go into long-term remission. However, detecting this disease in its early stages can be challenging. This pathology is burdened with recurrence and significant morbi mortality associated with several factors. Recurrence could be associated with male gender and vertebral involvement. Associated distant visceral hydatidosis and postoperative infectious complications could increase mortality. Larger-scale studies are needed to enhance our understanding of this rare condition, improve its management, and minimize factors that could negatively impact postoperative outcomes.",
"appendix": "Data availability\n\nFigshare: Chest Wall Hydatid Disease: Surgical management and risk Factors for Recurrence and Mortality. figshare. Dataset. https://doi.org/10.6084/m9.figshare.26384143.v1. 28\n\nThe project contains the following underlying data:\n\n• Base 2024.sav def (SPSS database of patients included in the study)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: CANNEVAS HYDATIDOSIS OF THE CHEST WALL. https://doi.org/10.6084/m9.figshare.26771605.v1. 29\n\nThis project contains the following extended data:\n\n• Cannevas hydatidosis of the chest wall (A data collection summary sheet)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nMaalej S, Belhabib D, Hantous S, et al.: Costo-vertebral hydatid disease: the role of MRI. Rev. Mal. Respir. 2003 Sep; 20(4): 614–617. PubMed Abstract\n\nWorld Health Organization: Aide-mémoire sur l’échinococcose (mis à jour en mai 2019). Wkly Epidemiol. Rec. Mai 2019; 94(48): 574–579.\n\nBoudaya MS, Mlika M, Chaari Z, et al.: Chest wall hydatidosis: a single institution experience. Arch. Clin. Infect. Dis. 2016 Aug; 11(4): e35134. Publisher Full Text\n\nTazi Z, Boujida N, Hamdouch N, et al.: Vertebral and spinal cord hydatidosis. Contribution of radiology and x-ray computed tomography. About 36 cases. J. Radiol. 1985 Mar; 66(3): 183–188. PubMed Abstract\n\nMiled M’rad KB, Bouricha A, Hantous S, et al.: Apport de l’imagerie au diagnostic du kyste hydatique de la paroi thoracique. J. Radiol. Mar 2003; 84: 143–146. PubMed Abstract\n\nSayek I, Tirnaksiz MB, Dogan R: Cystic hydatid disease: current trends in diagnosis and management. Surg. Today. 2004 Dec; 34(12): 987–996. PubMed Abstract | Publisher Full Text\n\nPamir MN, Ozduman K, Elmaci I: Spinal hydatid disease. Spinal Cord. 2002 Apr; 40(4): 153–160. Publisher Full Text\n\nBrichon P-Y: Thoracotomies latérales et postérolatérales. Encycl. Med. Chir. 2009; 4: 1–9. (Elsevier Masson, Paris), Techniques Chirurgicales - Thorax, 42-205. Publisher Full Text\n\nKhazim RM: Spinal hydatid disease. South. Med. J. 2006 Feb; 99(2): 114. Publisher Full Text\n\nKolsi M, Ghorbel M, Abdennadher M, et al.: Localisation costo-vertébrale compliquée d’une échinococcose multifocale. Intérêt de la chirurgie par voie antérieure. Rev. Mal. Respir. Sep 2005; 22(4): 673–676. PubMed Abstract | Publisher Full Text\n\nPrabhakar M, Acharya AJ, Modi DR, et al.: Spinal hydatid disease: a case series. J. Spinal Cord Med. 2005 Mar; 28(5): 426–431. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIşlekel S, Erçşahin Y, Zileli M, et al.: Spinal hydatid disease. Spinal Cord. 1998 Mar; 36(3): 166–170. Publisher Full Text\n\nZlitni M, Bouzidi R, Karray B, et al.: Hydatidose vertébrale: approche diagnostique et thérapeutique. Bull. Acad. Natl Med. Feb 2012; 196(2): 485–495. Publisher Full Text\n\nBouhaouala MH, Hendaoui L, Charfi MR, et al.: Hydatidose thoracique. EMC - Radiologie et imagerie médicale - Cardiovasculaire - Thoracique - Cervicale. janv 2007; 2(1): 1–17. Publisher Full Text\n\nKarray S, Zlitni M, Fowles JV, et al.: Vertebral hydatidosis and paraplegia. J. Bone Joint Surg. Br. 1990 Jan; 72-B(1): 84–88. Publisher Full Text\n\nChniti I: Prise en charge de l’echinococcose vertébrale [Thèse]. Médecine: Tunis.2019; 148.\n\nPamir MN, Ozduman K, Elmaci I: Spinal hydatid disease. Spinal Cord. 2002 Apr; 40(4): 153–160. Publisher Full Text\n\nLam KS, Faraj A, Mulholland RC, et al.: Medical decompression of vertebral hydatidosis. Spine. 1997 Sep; 22(17): 2050–2055. Publisher Full Text\n\nTurgut M: Hydatid disease of the spine: a survey study from turkey. Infection. 1997 Jul; 25(4): 221–226. PubMed Abstract | Publisher Full Text\n\nUlger S, Barut H, Tunc M, et al.: Radiation therapy for resistant sternal hydatid disease. Strahlenther. Onkol. 2013 Jun; 189(6): 508–509. PubMed Abstract | Publisher Full Text\n\nLezar S, Adil A, Zamiati W, et al.: Hydatidose vertebrale (à propos de 22 cas). Rev Maroc Chir Orthop Traumato. Jul 2006; 27: 14–17.\n\nZlitni M, Ezzaouia K, Lebib H, et al.: Hydatid cyst of bone: diagnosis and treatment. World J. Surg. 2001 Jan; 25(1): 75–82. Publisher Full Text\n\nEzzaouia K, Karray B, Bouabdallah M, et al.: Échinococcose vertébrale. À propos de 18 cas. Rev. Chir. Orthop. Reparatrice Appar. Mot. Nov 2007; 93(7): 62. Publisher Full Text\n\nZlitni M, Ezzaouia K, Bouzidi R, et al.: Manifestations osseuses des parasitoses. Encycl. Med. Chir. 2009; 4: 1–9. (Elsevier Masson, Paris), Appareil Locomoteur, 14-021-B-10. Publisher Full Text\n\nMiled M’rad KB, Bouricha A, Hantous S, et al.: Apport de l’imagerie au diagnostic du kyste hydatique de la paroi thoracique. J. Radiol. Mar 2003; 84: 143–146. PubMed Abstract\n\nTodorov T, Mechkov G, Vutova K, et al.: Factors influencing the response to chemotherapy in human cystic echinococcosis. Bull. World Health Organ. 1992 May; 70(3): 347–358. PubMed Abstract\n\nFkih L, Boussoffara L, Bedoui SA, et al.: Kyste hydatique costovertébral: pathologie bénigne ou maligne? Rev. Pneumol. Clin. Juin 2009; 65(3): 169–172. PubMed Abstract | Publisher Full Text\n\nRouis H: Chest Wall Hydatid Disease: Surgical management and risk Factors for Recurrence and Mortality. [Dataset]. figshare. 2024. Publisher Full Text\n\nRouis H: CANNEVAS HYDATIDOSIS OF THE CHEST WALL. Journal contribution. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "336420",
"date": "05 Nov 2024",
"name": "Alin Mihetiu",
"expertise": [
"Reviewer Expertise General Surgery"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe article is a good addition to previous literature regarding this disease. The structure is well organized and homogenous with a satisfactory statistical analysis. The discussion part provides additional data that reinforce the findings from the study. In my opinion the article has sufficient arguments to be published due to lack of large studies on this topic.\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": "336415",
"date": "06 Nov 2024",
"name": "Zied Chaari",
"expertise": [
"Reviewer Expertise Thoracic surgery / Chest wall Surgery / Hydatidosis / Lung and thoracic hydatidosis / Methodology / Statistics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI have read this manuscript entiteled \"Chest Wall Hydatid Disease: Surgical management and risk Factors for Recurrence and Mortality\" with a lot of interest This paper was about the chest wall localizations of hydatid disease and aimed to determine the results of its surgical management and to analyze the factors of recurrence and mortality through a multicentric and retrospective study including a total number of 49 patients.\n\nThis study included several centers including 4 surgical and 2 medical centers, which gives an idea of the rarity of this clinical entity of hydatidosis affecting the chest wall.\nBut, several points should be raised:\nAbstract section :\n\n- In this section, the authors would do better to clarify the definition of the term \"chest wall\" for inclusion of patients. For example: were clavicular, breast, intramedullary lesions in case of vertebral localization,... included?\n\n- The interest of your study should be apparent from the introduction and background. Indeed, the problem of hydatidosis of the chest wall implies an increased risk of locoregional recurrences, as has been presented in some series.\nIntroduction section :\n\n- In the introduction section, the authors reported that \"The long symptomatic silence of this disease...\" it would be better to detail if you are talking about hydatidosis in general (including pulmonary localizations which are often asymptomatic as reported in your text), or hydatid localizations particularly those of chest wall? if so, please report some references that cite the asymptomatic nature of hydatid localizations of the chest wall.\n\n- \"Bone lesions are extensive with a very progressive evolution and can lead to definitive neurological complications.\" Same remark about this sentence! the authors are dealing with (Bone) localization of hydatidosis or vertebral ones? hydatid involvement can very well be located in the long bones of the body, intraosseously, or even develop in the spongy bone, without having neurological complications as you mentioned!\n\n- The entire introduction section did not really reveal the resulting study objectives. Indeed, the concept of hydatid recurrence only appears in this sentence without insisting on it (admittedly very important to describe from an epidemiological point of view, frequency in the general population, and especially to introduce your major objective of your study). Please provide more information, references that support the need for your study.\n\n- On the other hand, I am afraid that the concept of \"chest wall\" reported in the introduction section would require more explanations, definitions... Indeed, the authors should clarify the terminology of this clinical entity as well as its characteristics.\n\nThis definition was given in the Methods section but there is a lack of precision regarding the definition of the word \"soft tissue\". A localization at the level of the soft tissues of the thorax was defined on what extent? from the neck to the abdomen? for the anterior localizations what was the limit attributed? for the posterior localizations was it a limit up to the level of the 12th rib or the vertebrae...? Please provide more details.\nMethods section :\n\n- \"Fifty records were retrieved.\" This sentence is a result, it should not be in the methods section.\n\n- Same remark for the Abstract section. In this section, the authors would do better to clarify the definition of the term \"chest wall\" for inclusion of patients. For example: were clavicular, breast, intramedullary lesions in case of vertebral localization,... included?\n\n- chest wall hydatidosis (CWH) abreviation was used and presented in the Methods section, and should be used towards the rest of the text. Please correct.\n\n- same remark about Hydatid Cyst abreviation (HC) used in Methods section while this abbreviation was stated more recently in the introduction part of the manuscript. Please make corrections.\n\n- Posterolateral thoracotomy abreviation does not figure in the text. It was first cited in Table 2 (without explanation at the bottom of the Table), and in discussion Section as (PLT) without explanation. Authors can use this abreviation for all \"Posterolateral Thoracotomy\" in the text.\n\n- \"We applied the inclusion and non-inclusion criteria and eliminated incomplete and unusable records. We retained fortynine patients operated on for chest wall hydatidosis.\" This section is a result. Please insert it in results section to apply inclusion, noninclusion and exclusion criteria.\n\nResults Section :\n\n- \"During the study period, 49 patients were operated on for CWH. The mean age of our population was 41 ? 17 years [8-76 years] with a male predominance.\". Authors can add the sex ratio for sex predominance, or put a reference to Table 1.\n\n- Authors used abreviation in Table 1 that are not explained at the bottom of the Table. Please add abreviation explanations.\n\n- Table 1 would be much more informative if the clinical signs were divided according to hydatid locations. Indeed, it is difficult to define and guess the clinical manifestations secondary to costal, bone, vertebral, or soft tissue involvement. Were there neurological manifestations for patients with isolated costal locations? Same remark for soft tissue involvement? Were the nervous manifestations exclusively secondary to vertebral hydatidosis?\n\n- Table 1: The radiological characteristics presented in the table would lack precision. Did the exploration interest all patients? All radiological explorations (thoracic X-ray, rib grill, ultrasound, MRI, scanner... were carried out for all patients?). It would be better to specify the % of patients who had explorations according to their achievements or not.\n\n- \"Abdominal ultrasound was performed in 44 cases as part of the etiological and extension assessment of the hydatid disease and showed a hepatic HC (GHARBI type IV) in nine cases.\" Since the authors did not mention in the methods section the bases of the Gharbi classification stated in the text, a reminder of this definition is necessary in the methods section beforehand. Otherwise, an insertion of a reference that describes this classification could be an option.\n\n- \"Atiered involvement of more than two ribs was observed in 43% of the cases, with a predominance of lesions at the Fourth to ninth rib level.\" Can the authors specify the exact percentage of this predominance? in the general population studied, and within the group of costal injuries. This would be much more informative.\n\n- I am afraid that there would be a miscalculation of the respective numbers of patients. Indeed, at the beginning of the Results section, the authors claimed to have reported 32 cases of vertebral localizations (between 11 exclusively vertebral cases, and 21 cases of costovertebral involvement). Further in the Results section, they mention \"The vertebral involvement was in the vertebral body in 21 cases and the intervertebral disc in two cases.\" which makes 23 cases.\n\nIn the same context, regarding costovertebral lesions (in the number expressed as 21 cases at the beginning of the Results section), the number of operated cases described was 18! (According to what was announced in the text: \"All patients were operated on. For costovertebral involvement, posterolateral thoracotomy was performed in 11 cases (61% of cases), a posterior approach in four cases (22% of cases), and a combined approach in 3 cases (17% of cases)\n\nThe results announced in the text are also in contradiction with those presented in Table 2 in which we find 11 costovertebral localizations (announced as 21 cases previously in the text). As well as the gestures involving the vertebrae (body, or transverse processes, or laminectomy), we can count 31 cases of gestures while in the text it was presented as 32 cases! (I quote: \"Bone involvement was vertebral (n=11), only costal (n=12), costovertebral (n=21) and sternal (n=2).\"\n\nDo the authors have any explanations for this difference?\n\n- \"A primordial time is the protection of the operating field by a scolicide solution. The main solutions were hypertonic saline and hydrogen peroxide (Figure 3).\" Figure 3 referred to by the authors does not show any scolicidal solution used during the surgical procedure. In addition, there is a lack of precision regarding the numbers (or %) of solutions used for the patients in this series.\n\n- \"The average length of hospitalization was 23.5 [5-55] days for isolated vertebral involvement, 19.8 [4-123] days for costovertebral involvement, 8.3 [1-35] days for isolated rib involvement, and three days for exclusive muscular involvement of hydatid disease.\" . Given the extreme values of hospitalization durations given in the text, the expression of the results would be better adapted by using the medians with the inter-quartille spaces 25% and 75% to have an idea on the median durations of hospitalizations. Please correct.\n\n- This study was analytical in order to determine the possible recurrence factors associated with surgery for chest wall hydatidosis. This characteristic was revealed in the Results section. Please mention the study character in the Methods section.\n\n- In the analytical part of the Results section, Table 3 included the univariate results of the possible factors associated with early recurrence. surprising results about Complete Costal resection that recur more quickly than a partial resection? Same thing for patients who had antiparasitic treatment postoperatively recur more quickly?\n\n- The authors were supposed to analyze the factors related to perioperative mortality in Table 4, while in the table, we find delays to death! All deaths were secondary to complications directly related to hydatid pathology? All cases of deaths reported (with delays even reaching 24 years for some patients) were directly involved in parietal hydatidosis?\n\nThe analytical study to determine mortality factors should focus primarily on cases of death that were directly related to the pathology itself.\n\nDiscussion section :\n\n- \"Recurrence is considered a poor prognostic factor in chest wall hydatid (CWH) disease\"... The abbreviation CWH has already been cited in the text, authors can use it without having to repeat the meaning of this abbreviation in the Discussion section.\n\n- \"This may be attributed to the small number of patients in our series (Ref 26)\". I think that you meant \"Their series referring to Todorov et al. study ?\n\n- The Discussion section should be better organized, initially talking about hydatid involvement of the chest wall in general, then, the authors can focus on each compartment separately, given their specificities, and especially the difference in surgical management according to their respective locations.\n\n- The authors did not explain the paradoxical results obtained concerning complete costal resection of hydatid lesions, which would be more likely to cause recurrences than partial resections?\n\n- There are other articles that have looked at the study of factors of recurrence of spinal surgery, and published recently like this study which traces the factors of recurrence in 39 operated patients. It would be interesting to compare your results with this recent series and therefore include it in your list of references. (Ref:1)\n\n- by well-organizing the discussion section, the authors can compare their results with similar series according to hydatid locations (the entire chest wall included, costal involvement, vertebral, costovertebral involvement, and soft tissue locations). This last location was not clearly discussed in the Discussion section (there is this reference that talks about it (Ref:2 ). Several series in the literature have studied and reported their results regarding spinal or vertebral hydatidosis with considerable numbers ( Ref:3, 4 and 5)\n\nStatistics :\n\n- Statistical revision must be made to correct Tables / the Text.\n\n- The expression of Means / Medians / Effectives and % should be revised according to the normality of distribution.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1297
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https://f1000research.com/articles/13-1296/v1
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29 Oct 24
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{
"type": "Research Article",
"title": "Young Adults Journey with Digital Fitness Tools-A Qualitative Study on Use of Fitness Tracking Device",
"authors": [
"Asees Kaur Gulati",
"Rachel Edna Lobo",
"Nihala N",
"Vishweshwara Bhat",
"Neha Bora",
"Vaishali K",
"Mukesh Kumar Sinha",
"Asees Kaur Gulati",
"Rachel Edna Lobo",
"Nihala N",
"Vishweshwara Bhat",
"Neha Bora",
"Vaishali K"
],
"abstract": "Background Physical activity trackers possess the potential to encourage increased physical activity. However, users often exhibit poor long-term adherence to these devices, which may stem from a lack of understanding of the factors influencing their use, as well as changes in health behavior. This study aims to provide new insights into the types of health-related apps and devices that young people discover, select, and utilize, along with the underlying reasons for their choices.\n\nMethods Young adults aged between 18-25 years reporting the use and nonuse of health apps and wearables were recruited and participated in focus group discussions about app choice, features, their perceptions towards the physical activity trackers, and reasons for continued use and for not using one. A total of Nine FGDS were conducted among users, nonusers, and former users of physical activity tracker usage. Data was recorded, transcribed, and analyzed for themes in an iterative approach.\n\nResults The physical activity tracker users group stated that they had a sense of achievement, validation, and other motivational feedback, which helped with adherence. All three groups (user, non-user, and former user) had similar concerns about cost, reliability, accuracy, and dependency. Former users also reported that the idea of accomplishing the goals would create anxiety and, in turn, harm the body. Former users and nonusers expressed their concerns regarding lack of time and loss of motivation to track their physical activity. Nonusers had issues with the functionality of the device (ease of use, battery, notifications, apps hang) and were also aware of all the health benefits of using wearables.\n\nConclusion Physical activity users group, former users group, and nonusers group shared concerns about accuracy, cost, and battery.",
"keywords": [
"Digital tracking",
"wearables",
"mobile health",
"physical activity",
"exercise",
"device",
"young adults",
"barriers and facilitators",
"fitness"
],
"content": "Introduction\n\nEngaging in regular physical activity is crucial for reducing the risk of noncommunicable diseases, maintaining both physical and cognitive functions, and improving overall well-being.1 Despite this, data from 2022 shows that about one-third of adults worldwide, roughly 1.8 billion people, did not meet the recommended activity levels.2 Insufficient physical activity is linked to a greater risk of various health issues, including major non-communicable diseases like coronary heart disease, type 2 diabetes, breast cancer, and colon cancer.3 It also leads to reduced life expectancy, making it a significant public health concern.4 Although numerous policies have been introduced to boost physical activity globally, there has been little progress in raising activity levels among adults. This situation underscores the need for renewed efforts and innovative methods to effectively promote physical activity and encourage a more active lifestyle across populations worldwide.\n\nIn today’s increasingly digital world, the integration of technology into daily life has revolutionized many areas, including fitness and health. Digital fitness tools, such as apps, wearables, and online platforms, have gained substantial popularity, especially among young adults.5–7 This demographic, known for being tech-savvy and highly focused on personal wellness, is adopting these innovations to increase physical activity, track fitness goals, and lead healthier lives. Wearable activity trackers, which are becoming more common globally, offer significant potential for supporting physical activity among a broad audience.5–7 Young people, in particular, are keen on finding, selecting, and utilizing mobile digital applications. These wearables enable users to monitor real-time physical activity, often using accelerometers, energy expenditure, heart rate, and other sensors.\n\nAdditionally, young adults are more likely than any other age group to use their phones for health-related information. Previous studies indicate that college students spend an average of 279 to 528 minutes per day using their devices with those who use their devices most frequently engaging with them nearly all the time.8–10 The use of cell phones is a prevalent behavior among individuals of various age groups. Wearables are defined as any body-worn computer designed to offer useful services while the user performs other tasks. These include activity trackers, pedometers, accelerometers, smartwatches, or smart clothing, which can be used to self-monitor and thereby improve physical activity levels and reduce sedentary behavior. Self-monitoring of activity levels has been associated with increased physical activity.6\n\nHowever, long-term adherence to using these tools remains limited. Moreover, the rise of digital fitness tools, or Fitness tracking device, is changing how young adults approach health and wellness. Despite their growing popularity and accessibility, there’s a lack of understanding of the deeper, experiential impact of these tools on users’ fitness journeys. Current research mostly quantifies usage patterns and general health outcomes but lacks qualitative insights into young adults’ personal experiences, challenges, and successes with these tools. Understanding these aspects can provide valuable insights for developers, healthcare professionals, and educators to enhance fitness-tracking device design and implementation, fostering more supportive environments for young adults to meet their fitness goals. This study aims to address this gap by exploring the unique stories of young adults using digital fitness tools, thereby contributing to a better understanding of their role in modern fitness culture.\n\n\nMethods\n\nThis study employs Focus Group Discussions (FGD) as a qualitative research method to delve into young adults’ distinct perceptions of digital fitness tools. By engaging participants in guided group discussions, the study explores how these individuals perceive and interact with technologies such as fitness apps and wearable devices. The objective is to gain deeper insights into their attitudes, motivations, and the impact of these tools on their fitness routines. Additionally, this manuscript adheres to the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist, ensuring transparency and comprehensiveness in the reporting of the study’s methodology and findings.11\n\nYoung, healthy individuals aged 18 to 25 years of both genders were selected to participate. The participants were divided into three groups: current users of physical activity trackers (apps or wearables), former users who had stopped using these trackers, and nonusers who had never used them. Differently, abled participants were excluded.\n\nUsing a purposive sampling technique, the study employed a saturation sampling approach. This qualitative sampling method involves recruiting participants until no new information is obtained, supporting the emergent nature of qualitative research and enabling simultaneous data collection and analysis. Separate focus group discussions were held for each group to encourage open and candid discussions about their perceptions of physical activity trackers. Individuals with recent injuries, fractures, surgeries, cardiopulmonary or metabolic issues, neurological complaints, or difficulties comprehending were excluded from the study. A brief demographic data was collected to capture basic information about participants before the FGD. They were categorized into three groups after screening, and written informed consent was obtained from each participant before the focus group discussion. This process includes outlining the study’s objectives, the criteria for participation, and any possible risks. Participants were assured of their confidentiality and the voluntary nature of their involvement, meaning they were free to withdraw at any time without consequence.\n\nAn interview guide was developed following an extensive literature search using various databases like\n\nMedline via PubMed, Scopus, Web of Science, and Embase. Face validation was carried out with eight members, including two physiotherapists involved in promoting physical activity, two exercise and sports science experts, two clinical psychologists, and two public health experts. The interview guide was modified based on the suggestions made by the expert panel members, and a final interview guide was prepared, which was used for conducting FGD. It consisted of open-ended questions and prompts eliciting rich narratives and insights from participants regarding the use of an activity tracker for physical activity.\n\nThe details of the moderator guide:\n\nParticipants were asked about their general thoughts on engaging in physical activity and exploring individual motivations and barriers. Discussions then shifted to participants’ opinions on tracking physical activity, evaluating the usefulness and relevance of monitoring habits, and their attitudes toward activity trackers.\n\nFor the non-user group, participants were asked to mention barriers preventing them from acquiring activity trackers, such as perceived cost, privacy concerns, relevance, and any other matters. They were also asked about their perception of physical activity.\n\nFor the user group, participants were asked to reflect on their experiences with activity trackers, discussing usability, effectiveness, and impacts on daily routines. They were asked to mention challenges faced while using the trackers and potential motivators for device/tracker use. They were also asked about their perceptions or beliefs regarding the use of these activity trackers.\n\nFor the former user group, participants were asked about their past experiences with activity trackers, including usage patterns and effectiveness. They were asked for reasons for discontinuing use, such as loss of interest or technical issues, and to share their feelings after stopping. Finally, they were asked what changes in wearable technology might encourage them to start using activity trackers again. Key questions for each group are depicted in supplementary Table.16\n\nParticipants who met the inclusion criteria were invited to take part in Focus Group Discussions (FGDs) at their convenience. The FGDs were led by three female physiotherapist researchers: AKG, REL, and NN, all of whom had received training in qualitative studies. Each moderator conducted discussions with different groups. Upon arrival, participants provided informed consent and demographic details (Table 1). The FGDs explored participants’ physical activity and experiences with wearable fitness trackers or other fitness apps. The nonuser group also discussed their knowledge and attitude towards using activity trackers. The FGDs, lasting between 45 to 90 minutes, involved a total of 56 participants and were divided into three categories: active users, non-users, and former users, with 5 to 8 participants in each group. Probes guided the discussions, which were audiotaped with participants’ consent, and supplemented by field notes. The interviews were recorded using handheld recorders (AE mini digital voice recorder, MP3 player compatible with 32GB extended TF card), and verbatim transcription was carried out.\n\nThe data was transcribed and analyzed using MS Excel. An iterative approach was employed for data analysis. The interview was coded in Microsoft Excel, and inductive content analysis was conducted. Codes were clustered into minor categories, which were further grouped into major categories. Thematic analysis was then carried out, wherein the raw data was thoroughly examined to derive themes without any restrictions.\n\nData analysis commenced after transcribing the first focus group discussion (FGD). Each transcript was meticulously reviewed, and each participant’s experience was identified and coded. Text segments were categorized, and relevant quotes were highlighted. Additionally, every transcript and corresponding field notes were analyzed, and new categories were added. At the same time, previously coded transcripts were checked for the presence of these new categories.\n\nThree researchers (NN, AKG, and REL) independently derived themes and analyzed all nine FGDs. while another group of researchers (MKS and NB) analyzed every second FGD. Once no new information was obtained from two consecutive FGDs and the primary analytic structure was considered stable, final verification was carried out by another two researchers (VK and VB). The research team discussed the categories and defined emerging themes and subthemes. The generated themes were cross-referenced with the field notes and original text to accurately represent the participants’ perceptions.\n\n\nResults\n\nThe participants’ characteristics are displayed in Table 1. A total of 9 FGDs were conducted for users, non-users, and former users. 2 FGD were conducted for the active user group (n=14), 3 FGD for the non-user group (n=26), and 4 FGD for the former user group (n=16). The participants reported using a wide range of apps, including Step Set Go, Samsung Health, Apple Fitness app, Google Fitbit, and Huawei Smartwatch (Table 1). The analysis of the interviews revealed numerous themes related to obtaining the app, using the app, and likes and dislikes about the app. The following five main themes contributed to perceptions of physical activity trackers, psychological aspects related to physical activity trackers, user-friendliness, health benefits of physical activity, and knowledge about physical activity post tracker usage. (Figure 1). A summary of the themes and codes is provided in Figures 2. Also, the details of the reporting from users, former users, and nonusers are depicted in Figure 2 and Table 2.\n\n\n\n▪ Knowledge about Physical activity- Stress relief, physical activity is a means to release stress, provide sleep benefits, improve daily efficiency, and healthy lifestyle.\n\n▪ Perceived need for tracking- Belief that daily activities and routines provide enough physical activity without the need for tracking, Satisfaction with current activity levels through daily chores, college, outdoor games, etc.\n\n▪ Opinions on Activity Trackers- Considered a waste of time and financially unnecessary, concerns about becoming overly reliant on technology, preference for maintaining natural daily routines, desire to minimize technology use, the belief from the family.\n\n▪ Barriers to Adoption- Perceived as not necessary, perceived as a financial burden, perceived as not worth the effort, about increased exposure to radiation perception, about the accuracy issue, Inability to use while sick\n\nParticipants who track their physical activity have a positive perception of these trackers, which motivates them to maintain consistency, specifically the objective feedback, e.g., steps, heart rate, calorie intake, sleep pattern, exercise intensity, water intake, and electrolyte balance. This made them feel confident about their physical activity as they could see the results and progress over time.\n\n‘I found it really motivational and surprisingly am not a consistent person in terms of exercise, but it has actually made me like a little more consistent towards at least walking or jogging or doing some physical activity everyday’\n\nDespite the positive feedback, there were some issues that wearable user’s group and wearable former users group mentioned, such as the app not providing enough notifications, the app hanging and crashes, accuracy issues, draining a lot of battery from the phone since the wearable is connected to the phone- which are not enough to encourage long time usage of this devices.\n\n‘If my smartwatch is working, then my app won’t be monitoring accurately.’\n\n‘Sometimes the apps hang, and they don’t show proper notifications or the steps, it happened to me today so you know the one thing I would like to change they should be consistent every day and it should show accurate results’\n\nAll three groups were asked to describe aspects of the device that they would like to change or are preventing them from making a purchase. Participants in all the groups mentioned that the cost may not be worth the benefits. They were also concerned that the devices were inaccurate based on their experiences.\n\nThe Wearable nonusers group reported that the trackers are unreliable and expensive, and since there is inconsistency in them doing physical activity, they don’t see the worth of getting one physical activity tracker.\n\n‘I need to first start getting very regular with my physical activity cause then it will just feel like a waste of money as some of them can be quite pricey also’\n\nParticipants in the wearables nonusers and former users group also expressed their concerns regarding the Internet connectivity that connects the wearable to the app in the phone. Some expressed that they forget to turn on their internet or are in no network range, leading to data inaccuracy.\n\n‘These apps require Internet connection. So sometimes we are in the area where we are not getting proper Internet connection and sometimes, we are there in that area for longer duration which might also hinder the effectiveness of tracking’\n\nPhysical activity wearable users discussed their positive attitudes and emotions towards their devices. Most felt like the device created a sense of achievement by earning rewards or points after completing a goal, which kept them motivated to keep exercising.\n\n‘Now my watch keeps telling me get up and move’\n\n‘Right now, I set it for 40 points but there is specific score which is 150 hard points for a week, and I always score above it and I always feel good about it. So, it’s more like a motivator for me to hit more than 150 points’\n\nThe physical activity tracker users group also described a sense of achievement when competing with their peers, which keeps them motivated to reach their goals.\n\n‘Also, within the app, you’re able to compete with other friends or other people so that also is kind of gives you a sense of fulfillment when you see your name with the number of steps you have and how much more it is compared to your friends’\n\nOne of the former physical activity tracker users also reported that the idea of accomplishing the goals would create anxiety and in turn harm the body\n\n‘I think that how much ever I eat, I should burn it or else it will cause harm to my body. I am quite particular in that way and then this creates anxiety in me that is why I am not into tracking’\n\nPhysical activity tracking users group enjoyed using the trackers more than the non-users group. However, users wore different brands of devices, leading to discrepancies in responses. Users group reported that the notifications sent through the tracker kept them motivated to keep exercising and accomplish their goal for the day.\n\n‘Now my watch keeps telling me get up and move’\n\n‘The app seems to give timely reminders that these many steps are remaining. Try your best, keep it up, finish it for the day.’\n\nAll the three groups expressed their annoyance with the functionality of the app connected with the tracker.\n\n‘Sometimes the apps hang, and they don’t show proper notifications or the steps. It’s happened to me today. So, you know, that’s one thing I would like to change they should be consistent every day and it should show accurate results’\n\nBased on their personal experience, both users and non-users group expressed concerns regarding the device’s accuracy.\n\n‘I use a watch, but I am not sure whether what they are telling me is correct or not because, some days I feel that I work more, but when I check the tracker, I see it’s 8000 steps but I feel like I’ve walked 10,000 steps so I am not sure whether it is reliable or not’\n\nAll the groups expressed a concern with the devices overestimating the amount of activity\n\n‘If you are like in a moving car or a bike, sometimes these steps add on even if you are not doing the physical activity’\n\nThe nonusers group also had a problem with the maintenance of the device.\n\n‘Maintenance of these equipment’s will also be something I consider. For example, if I get a smart watch, it will be more expensive in comparison, and then I will have to take care of it.’\n\nFormer users group expressed concerns that led them to stop using the physical activity tracker. Some did not have the time because of their professional workload, some expressed annoyance with the charging issue, and some lost motivation over time as they kept forgetting to wear their wearables.\n\nWearable users and former users group described a certain behavior change after tracking their physical activity. They were more aware of their physical health and work more towards it. They have reported being more adherent to things in life.\n\n‘We are adherent to that 10,000 or 11,000 steps that adherence will help us like little more physically active than what we were previously with’\n\nIn this study, we explore the hypothesis that the demographic composition of our participants significantly shapes the inclination towards user-friendly interfaces in health monitoring devices. Specifically, we consider variables such as age, height, weight, body mass index (BMI), and fitness tracker usage habits. Our cohort predominantly comprises younger individuals whose engagement with technology offers valuable insights into device interaction preferences. Age plays a key role in how people engage with technology, with younger users generally being more receptive to digital interfaces. Understanding age distribution helps tailor device usability for better engagement and satisfaction. Incorporating anthropometric metrics enables personalized device recommendations that align with individual health profiles. Analyzing users’ interactions with fitness trackers—active, discontinued, or non-users—provides insights into the factors that encourage or hinder consistent usage. This information is essential for designing interfaces that effectively meet user needs and overcome challenges with fitness trackers. The aspiration to achieve aesthetic appeal and sustain a healthy physique acts as a catalyzing factor, fostering increased engagement in physical activities across diverse platforms and modalities. This alignment of digital integration with fitness aspirations elucidates a synergistic relationship that enhances the overall enthusiasm toward physical activity participation.\n\nNonusers group have also recognized the potential of these physical activity trackers and encouraged to do physical activity as it prevents diseases.\n\n‘I heard that some people saved their own lives because they had some kind of a tracking device on them like the Apple version. Like one person was saved from having a cardiac arrest and it also helps people who are struggling with some physical condition like maybe diabetes or heart problem’\n\nSome have also expressed concerns that youngsters get deeply involved in tracking that can lead to misusing of it which might then affect their mental and physical health.\n\nBoth physical activity tracker users and non-users group expressed positive opinions on physical activity. The most common ones stated were that it is a state of physical as well as mental well-being that improves one’s quality of life and helps to prevent diseases. Many of them also reported that it brings a sense of peace and helps to relieve stress, gives a calming effect, and gives a sense of peace to mind and body, which improves their overall wellness.\n\nThe participants were asked about their source of knowledge on physical activity. Some expressed that they learned about it from online platforms. Some learnt about it from their peer groups.\n\n\nDiscussion\n\nThis qualitative study delves into the experiences of young adults using digital fitness tools. The study identifies various factors from the perspectives of users, former users and nonusers of digital fitness trackers. The findings from this study provide valuable insights into how young adults utilize digital fitness tools. As the use of these technologies becomes more prevalent, it is crucial to understand their impact on health behaviors and lifestyle choices among young people.\n\nParticipants reported that digital fitness tools significantly enhance their motivation to engage in physical activity. The ability to track progress in real-time, set personalized goals, and receive immediate feedback were highlighted as key motivators that help them stay accountable. This aligns with existing literature, suggesting that digital fitness apps’ self-monitoring features can improve adherence to exercise regimens.12,13\n\nFurthermore, social connectivity was an important theme in the discussions. Many participants expressed that the social features in these tools, such as sharing achievements with friends and participating in virtual challenges, keep motivation on the higher side, and user engagement is enhanced. This finding is consistent with previous research.14\n\nHowever, the study also uncovered challenges associated with the use of activity trackers. Participants indicated varying levels of technological proficiency, which influenced their overall experience with the trackers. More tech-savvy individuals could leverage advanced features to enhance their fitness journey, while others felt overwhelmed or frustrated by the technology. This difference underscores the importance of digital fitness tools with user-friendly interfaces catering to different levels of technological literacy.\n\n\nConclusion\n\nOur findings help to understand the characteristics that appeal to physical activity tracker users and the viewpoints of non-users and former users. All three groups expressed concerns about these devices’ accuracy, cost, and battery life. Non-users’ perspectives mainly focused on functionality, materialism, and differences in motivation compared to users. These varied perceptions of active users, non-users, and former users towards wearables will aid future physical activity research and interventions related to digital behavior.\n\nThis study was approved by the Institutional Ethics Committee of Kasturba Medical College and Kasturba Hospital Manipal Institutional Ethics Committee-2 (Student Research) (IEC2 508/2022) on December 2nd 2022. This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The study participants were categorized into three groups after screening, and written informed consent was obtained from each participant before the focus group discussion. Participants were assured of their confidentiality and the voluntary nature of their involvement, meaning they were free to withdraw at any time without consequence.\n\nConceptualization and methodology - AKG, NN, REL, VB, NB, VK, and MKS; formal analysis, AKG, NN, REL, and MKS; writing original draft - AKG, NN, REL, VB, NB, VK, and MKS; Review and editing - AKG, NN, REL, VB, NB, VK, and MKS; supervision, MKS, VK, NB, and VB\n\nAll authors have read, agreed, and reviewed the final version of the manuscript.",
"appendix": "Data availability\n\nAll data underlying the results are available on Figshare.\n\n1. Data Excell sheet for Young Adults Journey with Digital Fitness Tools. figshare. Dataset. https://doi.org/10.6084/m9.figshare.27249390.v2. 15\n\nThis study contains the following underlying data:\n\n• Data Excell sheet for Young Adults Journey with Digital Fitness Tools\n\nData are available under the terms of the CCO License.\n\n2. Young adults journey with digital fitness tools-A qualitative study on use of fitness tracking device, figshare. Dataset. https://doi.org/10.6084/m9.figshare.27274944.v1. 16\n\nThis study contains the following extended data:\n\n• Key questions in the moderator guide (Extended data (Moderator guide).docx)\n\nData are available under the terms of the CCO License.\n\n\nReferences\n\nStrain T, Flaxman S, Guthold R, et al.: National, regional, and global trends in insufficient physical activity among adults from 2000 to 2022: a pooled analysis of 507 population-based surveys with 5· 7 million participants. Lancet Glob. Health. 2024 Aug 1; 12(8): e1232–e1243. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWHO reports: [Accessed on 24th July 2024]. Reference Source\n\nLee IM, Shiroma EJ, Lobelo F, et al.: Effect of physical inactivity on major non-communicable diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 2012 Jul 21; 380(9838): 219–229. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMin C, Yoo DM, Wee JH, et al.: Mortality and cause of death in physical activity and insufficient physical activity participants: A longitudinal follow-up study using a national health screening cohort. BMC Public Health. 2020 Dec; 20: 1. Publisher Full Text\n\nBurford K, Golaszewski NM, Bartholomew J: “I shy away from them because they are very identifiable”: A qualitative study exploring user and non-user’s perceptions of wearable activity trackers. Digit. Health. 2021 Nov; 7: 20552076211054922. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWilde LJ, Ward G, Sewell L, et al.: Apps and wearables for monitoring physical activity and sedentary behaviour: A qualitative systematic review protocol on barriers and facilitators. Digit. Health. 2018 May; 4: 2055207618776454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFabbrizio A, Fucarino A, Cantoia M, et al.: Smart devices for health and wellness applied to tele-exercise: an overview of new trends and technologies such as IoT and AI. Healthcare. 2023 Jun 20; Vol. 11(12): p. 1805. MDPI. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBarkley JE, Lepp A: Mobile phone use among college students is a sedentary leisure behavior which may interfere with exercise. Comput. Hum. Behav. 2016 Mar 1; 56: 29–33. Publisher Full Text\n\nLepp A, Barkley JE, Karpinski AC: The relationship between cell phone use, academic performance, anxiety, and satisfaction with life in college students. Comput. Hum. Behav. 2014 Feb 1; 31: 343–350. Publisher Full Text\n\nFennell C, Barkley JE, Lepp A: The relationship between cell phone use, physical activity, and sedentary behavior in adults aged 18–80. Comput. Hum. Behav. 2019 Jan 1; 90: 53–59. Publisher Full Text\n\nTong A, Sainsbury P, Craig J: Consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups. Int. J. Qual. Health Care. 2007 Dec 1; 19(6): 349–357. PubMed Abstract | Publisher Full Text\n\nHu J, He W, Zhang J, et al.: Examining the impacts of fitness app features on user well-being. Inf. Manag. 2023 Jul 1; 60(5): 103796. Publisher Full Text\n\nVoth EC, Oelke ND, Jung ME: A theory-based exercise app to enhance exercise adherence: a pilot study. JMIR Mhealth Uhealth. 2016 Jun 15; 4(2): e4997. Publisher Full Text\n\nTong HL, Laranjo L: The use of social features in mobile health interventions to promote physical activity: a systematic review. NPJ Digit. Med. 2018 Sep 4; 1(1): 43. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSinha MK: Data Excell sheet for Young Adults Journey with Digital Fitness Tools. Dataset. figshare. 2024. Publisher Full Text\n\nSinha MK: Extended data (Moderator guide).docx. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "337150",
"date": "11 Nov 2024",
"name": "Aishwarya Nair",
"expertise": [
"Reviewer Expertise Pulmonary rehabilitation",
"Fitness",
"Critical care physiotherapy",
"cardiac 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\nSUMMARY\nThis study discusses the importance of physical activity and its impact on the young generation. As the current generation is perfectly synced with technology, they have a variety of applications at their disposal which allows them to track the levels of their physical activity. The study describes the complete protocol for selection of participants, the methods of FGD and the proceedings of the discussions. Clarity on the domains of the interview are provided clearly. The methodology is at par with the guideline issued for FGDs. A few clarifications are needed for the inclusion and exclusion criteria which has been described below. The details of the interview guide development is particularly well defined which is appreciated. The thematic diagram denoting the various data from the FGD is unique and attractive. It allows the reader to understand the study in a quick glance. It is better to avoid direct quotes from the participants as it introduces a certain casualness in the scientific document.\n\nMAJOR REVISION-\nINTRODUCTION 1. A few studies that reported the reason for discontinuing the use of fitness can be added to the introduction. This will provide strong support for the need of this study.\n\nMETHODOLOGY 1. Please justify why individuals with recent injuries or fractures have been excluded especially since this study aims to understand their journey with the fitness apps. A recent journey may not negatively impact or hinder the past experience of using these fitness apps.\nDISCUSSION/CONCLUSION: 1. Please add the strengths and limitations of this study with a note on scope for future studies.\nMINOR REVISION: 1. A complete grammar check can be done for the document.\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": "337153",
"date": "11 Nov 2024",
"name": "Dr. Trapthi Kamath",
"expertise": [
"Reviewer Expertise neuro physiotherapy"
],
"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 research investigates the experiences young adults with digital fitness tools mainly FGDs.By examining data from young adults who currently use,have previously used or do not use wearable fitness trackers.The research looks at how these devices influence physical activity habits,motivation and perceptions.The results indicate wearables can encourage physical activity through goal setting ,feedback and social interactions,such as device accuracy ,cost and technical issue for long term .The qualitative approach offers valuable insights into the complex experiences and attitudes of young adults toward wearable fitness tolls ,emphasizing the necessary designs that are user friendly and accesible. key insights- motivation,challenges,reach out, technological engagement. Strengthen of the study-diverse participant group areas of improvement-thematic consolidation Additionally add practical implications\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/13-1296
|
https://f1000research.com/articles/13-1295/v1
|
29 Oct 24
|
{
"type": "Research Article",
"title": "Awareness of deleterious oral habits and knowledge of habit breaking appliance among parents in Alkharj - A cross sectional study",
"authors": [
"Sultan Abdulrahman Almalki",
"Inderjit Murugendrappa Gowdar",
"Saeed N Asiri",
"Praveen Jodalli",
"Bashar Ayed Alanazi",
"Osama abdullah Alqahtani",
"Fahad Radhi Alanazi",
"Sultan Abdulrahman Almalki",
"Inderjit Murugendrappa Gowdar",
"Saeed N Asiri",
"Bashar Ayed Alanazi",
"Osama abdullah Alqahtani",
"Fahad Radhi Alanazi"
],
"abstract": "Background Actions that are repetitive and being practiced automatically are called habits. Oral habits can be classified as normal or deleterious. Oral health education starts from footprints of awareness. Growing children require appropriate guidance for healthy growth and maintenance of their teeth, which makes the parent an active participant in the prevention and treatment of malocclusion and thus is majorly affected by their knowledge and attitude regarding various deleterious oral habits and habit breaking appliances.\n\nAim To assess and compare awareness of deleterious oral habits and knowledge of habit breaking appliance, among parents at Alkharj Saudi Arabia.\n\nMethodology Study assessed awareness of deleterious oral habits and knowledge of habit breaking appliances among parents in Alkharj, Saudi Arabia.\n\nResults\n\nConclusion Majority of the parents were aware of different deleterious oral habits but not aware of the dimensions of interventions like types of appliances, duration of use, etc. without knowing mentioned facts, in future which leads to development of malocclusion which probably requires orthodontic, surgical or prosthetic intervention correcting the outcomes of oral deleterious habits.",
"keywords": [
"oral appliance",
"oral health",
"dental appliance",
"habits"
],
"content": "Introduction\n\nActions that are repetitive and being practiced automatically are called habits. Oral habits are learned patterns of muscle contraction and have a very complex nature.1 Oral habits can be classified as normal or deleterious. Nasal breathing, chewing, and swallowing are regarded as physiological and functional habits, since they contribute to the establishment of normal occlusion, favoring the harmonic facial growth without deviations.2 However, habits which influences dentofacial structures and results in malocclusion such as nail biting, mouth breathing, thumb sucking, finger sucking, tongue thrusting, lip biting, or lip sucking, bruxism are called deleterious or adverse oral habits.3,4 These deleterious habits have regular tendency and is hard to give up. These habits are mostly seen in the early childhood and mixed dentition stages.5\n\nMalocclusion is the misalignment of teeth resulting in esthetic and functional alterations. The common causes of malocclusion include genetic, environmental, systemic causes, and harmful oral habits.6 Hence, oral habits are the primary cause of dentofacial deformities in children, require immediate attention for prevention. Knowledge and awareness are essential prerequisites for changes in behavior related to health and disease anticipation.7\n\nNowadays the focus in dentistry is changing towards prevention of disease rather than its treatment and the public’s role has changed from passive recipient to active participant in prevention.8 Children with extracted anterior teeth along with the habit of thumb sucking require attention commonly for aesthetics, function, and space maintenance but also must be given an appliance for habit breaking. The line of treatment for these habits includes the removal of the etiology, retraining exercises, and the use of mechanical restraining appliances.9\n\nParents are role models for their children. They can play an important role in developing healthy oral habits in children.10 Oral health education starts from footprints of awareness. Growing children require appropriate guidance for healthy growth and maintenance of their teeth, which makes the parent an active participant in the prevention and treatment of malocclusion and thus is majorly affected by their knowledge and attitude regarding various deleterious oral habits and habit breaking appliances. No data are available regarding parental awareness of deleterious oral habits and habit breaking appliances among Saudi parents. Hence, the present study was conducted to assess the parental knowledge and awareness of deleterious oral habits and habit breaking appliance among Alkharj parents.\n\n\nMethods\n\nThe survey is designed, analyzed and interpreted according the STROBE checklist.\n\nAn observational, descriptive cross-sectional survey was conducted on adult population to assess the awareness oof deleterious oral habits and their knowledge on habit breaking appliances in Alkharj, Saudi Arabia.\n\nData were collected using a self-designed structured questionnaire comprising 12 questions, divided into three sections. First section gathered basic demographic details of the participants; the second section included four questions aimed at assessing participants’ awareness of harmful oral habits. The final section contained six questions focused on participants’ knowledge regarding malocclusion and various appliances used to correct these issues.\n\nThe questions were translated into Arabic and subsequently back-translated into English by language experts proficient in both languages. This back-translation method was employed to verify the translation’s validity and ensure linguistic equivalence. Content validity was assessed by two subject matter experts in orthodontics, and the Content Validity Index (CVI) for the entire scale was calculated. A satisfactory level of agreement was achieved, with a CVI of 0.87 among the panellists.\n\nA pilot survey was conducted, during which the questionnaire was administered randomly to ten parents. After two days, the same questionnaire was readministered to these parents to evaluate reliability using the test-retest method. The computed reliability value was 0.89. Additionally, Cronbach’s α was applied to assess internal consistency, yielding a value of 0.84, indicating a high level of correlation.\n\nParents visiting the screening area of the College of Dentistry in Alkharj, along with their children seeking treatment, were approached to participate in the survey after meeting the eligibility criteria. A scan code for the questionnaire was sent to their Messenger, WhatsApp, Snapchat, or email. The questionnaire included multiple sections: a description of the survey, a voluntary written consent form, the survey questions, and a thank-you note. To enhance the response rate, three reminders were sent to the parents. A questionnaire was sent to 400 parents, of whom 376 completed it, resulting in a response rate of 89%. The primary reason for non-response was reported as a lack of time.\n\nValidation of questionnaire: Based on the detailed analysis of literature, structured questionnaire was framed with the assistance and guidance of panel of academic experts to achieve validated and relevant questionnaire. To validate the questionnaire, questions were prepared in English language initially and translated to Arabic language & it was back translated again to English.\n\nSample size was calculated by using the formula\n\nWhere,\n\nZ = 1.96 (Confidence Level or 5% level of significance)\n\np = awareness level of deleterious habits at 60% = 0.60\n\nd = Precision limit or proportion of sampling error which is usually 5% confidence limit. = 0.05\n\nBy substituting the values, sample size of 368 was found to be sufficient.\n\nQuestionnaire: An anonymous, objective type questionnaire was requested to fill by parents without providing any information. Questionnaire had 3 parts Personal information (gender, age, place and educational status), awareness about deleterious habits and knowledge of habit breaking appliance. Unmarried people were not included in the study only parents who have children above 7 years and parents who were residing in Alkharj were included.\n\nMethod: Questionnaire scan code was prepared and was asked to scan when parents came with children for treatment at screening area of College of Dentistry. Parents were asked to send the link to friends and groups in Alkharj through cross platform messengers WhatsApp, snap chat and email which also had a consent form and explanation about the study. A total of 400 questionnaires were sent out of which 376 returned giving a response rate of 89% out of which 7 questionnaire were incomplete and were excluded hence a total of 369 responses were considered.\n\nStatistical analysis: Descriptive statistics were computed and data were analyzed statistically using chi square test with 95% confidence interval and p value less than 0.05 was considered as statistically significant.\n\n\nResults\n\nThere are total of 369 participants in the study out of which 163 (44.2%) are males and 206 (55.8%) are females distribution of study participants according to age is presented in Table 1.\n\nTable 2 shows awareness of study participants about various deleterious habits. 80% of study participants were aware about thumb sucking habit and mouth breathing habits. Whereas 75.6% of study participants were aware about bruxism and only 34.1% of study participants are aware about tongue thrusting habit.\n\nTable 3 shows response of study participants about malocclusion and habit breaking appliance. 46.9% of study subjects are not sure whether adverse habits results in malocclusion or not. 55.3% of participants were not sure that deleterious habits can be treated with appliances are not. 84.0% of participants are not sure about the duration of usage of an habit breaking appliance. 68.9% of study subjects are not sure of the usage of habit breaking appliance in preventing malocclusion. 52.8% of subjects told that Adverse habits can be due to feeling of insecurity and anxiety. 66.1% of subjects think that psychological counseling will benefit in breaking adverse oral habits.\n\nTable 4 shows comparison of responses of study participants according to gender and age group. Age group showed statistically significant differences with all the questions evaluated whereas according to gender few of the responses were statistically significant as shown in the table.\n\n\nDiscussion\n\nAn automatic act adapted by practice and performed with repetition is called as habit. These habits can be deleterious and can be the major contributing act leads to the development of dental malocclusion.11 Actions includes sucking of digits, mouth breathing, habits associated with pacifiers and bottle use, lip biting and suckling habits, tongue thrusting, teeth clenching and if these acts, performed in repetition manifests as an automated act to become oral deleterious habits.12 Among all, thumb suckling and tongue thrusting habits are most commonly prevailed acts giving rise to variety of oro-facial malformations.13\n\nChildren practicing the habits are generally unaware of the deleterious habits and their long-term impact of any habit and parents should take vital role by acting with timely intervention leading to the cessation of habit.9 Present study attempts to assess the knowledge and awareness of habits and habit breaking appliances among Alkharj parents Saudi Arabia.\n\nAmong 369 participants in the study, 163 were males and 206 were females and majority of the participants were middle aged individuals aged between 30 to 50 years. Majority of the study participants were aware of thumb sucking habit as it is highly prevalent and same observations prevailed with mouth breathing and bruxism but surprisingly only 34% among the participants were aware of the existence of tongue thrusting as a habit which is noted to be prevalent among different population and current study findings is in accordance with findings of Prasanna et al.9\n\nOn assessment of awareness of habits and habit breaking appliances only 50% of the participants were aware of adverse habits and their manifestations and nearly 47 % of the participants were not sure of the effects and outcomes of the deleterious habits which can adversely affects the maxillofacial development and this mirrored with the findings of Hedge et al.14 and further, 55% of the participants were not sure of interventional aspects involving habit breaking appliances. Assessing the observations on duration of administration of treatment involving habit breaking appliances, nearly 70% of the participants were totally unaware of the concepts and trends of appliances and similar findings is noted by Chonat et al.15\n\nOn observations on psychological dimensions of the oral deleterious habits, majority of the participants were able to relate the existence of secondary factors like insecurity and anxiety as it is a established fact that habits will have psychological association and majority of the participants also believe psychological counseling benefits in breaking adverse oral habits and contrasting results been noted by Gangurde et al, probably the difference is accounted by selected study population.16\n\nOn summarizing the current study results majority of the parents were aware of different deleterious adverse oral habits but not aware of the dimensions of interventions like types of appliances, duration of use etc without knowing mentioned facts in future which leads to development of malocclusion which probably requires orthodontic, surgical or prosthetic intervention correcting the outcomes of oral deleterious habits. To spread awareness among parents different awareness programmes involving different strata of the society should be conducted by various government and non-government organizations to impact prevention. Those programmes may include awareness camps, descriptive digital demonstrations, community lectures, publicizing on social media, conceptual facts published in newspapers, displaying posters in public platforms and also timely updating information on the same to prevent long term impact of oral deleterious habits.\n\n\nEthics and consent\n\nThe study protocol received approval from the Institutional Review Board (IRB) of Prince Sattam Bin Abdul Aziz University, under approval number SCBR-198/2023 on 19/12/2023 Voluntary written informed consent was obtained from all participants using the electronic informed consent system prior to accessing the online survey link. The consent form clearly described the purpose of the survey and amount of time required to complete the questionnaire in simple and understandable language. Participants were informed that they could withdraw from the survey at any time without penalty and that their personal information would be kept confidential.",
"appendix": "Data availability\n\nAwareness of deleterious oral habits and knowledge of habit breaking appliance among parents in Alkharj - A cross sectional study. figshare. https://doi.org/10.6084/m9.figshare.27111499. 17\n\nThis project contains the following underlying data:\n\n1. Ortho excel sheet.xlsx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nAwareness of deleterious oral habits and knowledge of habit breaking appliance among parents in Alkharj - A cross sectional study. figshare. Dataset 2024. https://doi.org/10.6084/m9.figshare.27111499. 17\n\nThis project contains the following extended data:\n\n1. Ortho questionnaire.dox\n\n2. Questionnaire translated.dox\n\n3. STROBE ckecklist.doc\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\nAcknowledgement\n\nNil.\n\n\nReferences\n\nSharma S, Bansal A, Asopa K: Prevalence of Oral Habits among Eleven to Thirteen Years Old Children in Jaipur. Int J ClinPediatr Dent. 2015; 8(3): 208–210.\n\nVishnu Prasanna SG, Ravindran V, Keerthi Sasanka L: Knowledge and Awareness on Habits and Habit Breaking Appliances Among Parents-A Questionnaire Survey. J Res Med Dent Sci. 2020; 8(7): 122–128.\n\nKamdar RJ, Al-Shahrani I: Damaging oral habits. J Int Oral Health. 2015; 7(4): 85–87. PubMed Abstract\n\nSuhani RD, Suhani MF, Muntean A, et al.: Deleterious oral habits in children with hearing impairment. Clujul med. 2015; 88: 403–407. PubMed Abstract | Publisher Full Text\n\nAli F, Soni S, Kaur G, et al.: Oral habits in relation to malocclusions: A review. Int J Health Sci. 2021; 5(S2): 230–238. Publisher Full Text\n\nGrippaudo C, Paolantonio EG, Antonini G, et al.: Association between oral habits, mouth breathing and malocclusion. Acta Otorhinolaryngol Ital. 2016 Oct; 36(5): 386–394. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZawadzka B: Swiadomość i wiedza warunkiem prozdrowotnych postaw pracowników w miejscu pracy [Awareness and knowledge as prerequisites for health-oriented behavior]. Med Pr. 2002; 53(6): 489–493. PubMed Abstract\n\nPolverini PJ: A curriculum for the new dental practitioner: preparing dentists for a prospective oral health care environment. Am J Public Health. 2012; 102(2): e1–e3. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVishnu Prasanna SG, Ravindran V, KeerthiSasanka L: Knowledge and Awareness on Habits and Habit Breaking Appliances Among Parents-A Questionnaire Survey. J Res Med Dent Sci. 2020; 8(7): 122–128.\n\nAlamoudi RM, Showlag RA, Almujil NJ, et al.: The impact of parental oral health behaviors on the oral health of children. Int J Community Med Public Health. 2023Oct.6; 10(11): 4451–4456. Publisher Full Text Reference Source\n\nBoeck EM, Pizzol KEDC, Barbosa EGP, et al.: Prevalência de máoclusãoemcrianças de 3 a 6 anosportadoras de hábito de sucção de dedo e/ouchupeta. Rev Odontol UNESP. 2013; 42(2): 110–116. Publisher Full Text\n\nGarde JB, Suryavanshi RK, Jawale BA, et al.: An epidemiological study to know the prevalence of deleterious oral habits among 6 to 12 year old children. J Int Oral Health. 2014 Feb; 6(1): 39–43. PubMed Abstract\n\nSuhani RD, Suhani MF, Muntean A, et al.: Deleterious oral habits in children with hearing impairment. Clujul Med. 2015; 88(3): 403–407. PubMed Abstract | Publisher Full Text\n\nHegde AM, Xavier AM: Childhood Habits: Ignorance is not Bliss- A Prevalence Study. Int J Clin Pediatr Dent. 2009 Jan; 2(1): 26–29. Publisher Full Text\n\nVasanthakumari A, Arumugam S, Saket P, et al.: Awareness and Attitude of Parents regarding Malocclusion and Early Interception of Oral Habits-associated Dentofacial Deformity in Children. World J Dent. 2022; 13(3): 266–270. Publisher Full Text\n\nGangurde VP, Gaikwad S: Knowledge and awareness of habits and appliances for breaking habits: A questionnaire survey. Eur Chem Bull. 2023; 12(1): 2902–2907.\n\nPraveen J: Awareness of deleterious oral habits and knowledge of habit breaking appliance among parents in Alkharj - A cross sectional study. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "340598",
"date": "19 Nov 2024",
"name": "Thippeswamy HM",
"expertise": [
"Reviewer Expertise Public Health dentist"
],
"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 found to be good. introduction explained with seminar approach and content found to be good. Study methodology presented well. Administration of questionnaire to the parents explained very well. validation, sample size done well. overall methodology seems to be good. Results presented tabular form. Inferential statistics values would have mentioned then and there, instead of making separate table 4. Discussion and conclusion written 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? 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": "340591",
"date": "22 Nov 2024",
"name": "Omnia Abdallah",
"expertise": [
"Reviewer Expertise microbiology",
"biotechnology",
"nanotechnology"
],
"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\nhighly informative, please proceed with indexing\nAwareness of deleterious oral habits and knowledge of habit breaking appliance among parents in Alkharj - A cross sectional study The authors have indicated the gap between what science have indicated and the parents knowledge and ability to convey this information to their children minor revisions 1- the authors need to share the sections of the survey if not the whole one as supplementary material 2- the authors need to add a further paragraph to the discussion as their own conclusion and future implementation of such 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?\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": "340595",
"date": "22 Nov 2024",
"name": "Tanushree Dalvi",
"expertise": [
"Reviewer Expertise Epidemiological investigations",
"Health Education",
"cross-sectional studies",
"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\nThe manuscript is well structured and drafted according to the STROBE guidelines. Title and abstract is informative. The introduction highlights the need for the study with aim. The authors have explained in detail about the validation of the instrument of data collection, the study design and the scientific estimation of sample size with formula. The method of data collection is explained in depth to allow replication. The tests for statistical analysis have been specified according to the type of data obtained. The results are well tabulated and the characteristics of study participants have been mentioned. The authors have summarised the key results in discussion and also cited studies with similar findings. Recommendation is provided for executing similar research for future studies. Ethical approval is obtained and appropriate referne ID id mentioned along with the consent process in detail.\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": "340596",
"date": "05 Dec 2024",
"name": "Sana Bint Aziz",
"expertise": [
"Reviewer Expertise Orthodontics & Dentofacial Orthopedics"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript titled \" Awareness of deleterious oral habits and knowledge of habit breaking appliance among parents in Alkharj - A cross sectional study\" is interesting as awareness of deleterious oral habits is important for the prevention and timely management. The manuscript is written well, however there are certain areas that need some revisions.\nAbstract:\nNo result is provided. Please include in brief the findings of the study in the result section of the abstract.\nMethods:\nCheck spellings in line 'to assess the awareness oof deleterious oral habits\" and \"Date collection\"\nPlease provide a reference for the Content Validity Index (CVI) and include it in the manuscript.\nThe methods section needs to be reframed to clearly state as to how many times the questionnaire was validated and how many questionnaires were prepared. Certain sub-headings like validation of questionnaire, data collection, method, and questionnaire are overlapping and repetitive in nature, resulting in confusion about the no. of questionnaires used in the study. For instance, If a pilot study was conducted before the main survey then it can be explained in detail in the beginning only under a sub-heading of Pilot study.\nSample Size - Please mention whether the sample size calculation was done a priori (before the study) or later.\nResults Please break the sentence in two, or join the two sentences using a conjunction such as 'and'... \"There are total of 369 participants in the study out of which 163 (44.2%) are males and 206 (55.8%) are females distribution of study participants according to age is presented in Table 1.\"\nDiscussion Limitations of the study has not been included. Please include, if any.\nAlso, a short conclusion at the end of the manuscript is needed.\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/13-1295
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https://f1000research.com/articles/12-593/v1
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02 Jun 23
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{
"type": "Research Article",
"title": "Sustainability performance assessment of sago industry supply chain using a multi-criteria adaptive fuzzy inference model",
"authors": [
"Yusmiati Yusmiati",
"Machfud Machfud",
"Marimin Marimin",
"Titi Candra Sunarti",
"Marimin Marimin",
"Titi Candra Sunarti"
],
"abstract": "Background: Sustainable supply chains are more competitive than conventional supply chains. Supply chain sustainability performance needs to be carried out to determine sustainability under current conditions and to design appropriate strategies to increase sustainability. This study aims to design a sustainability performance assessment model for the sago agro-industry supply chain and identify critical indicators for sustainability improvement. Methods: The Fuzzy Inference System (FIS) evaluates sustainability on three levels: economic, social, and environmental. The Adaptive Neuro-Fuzzy Inference System (ANFIS) is then used to aggregate the overall sustainability performance. The cosine amplitude method (CAM) was used to analyze key indicators. This study assessed the sustainability performance on industrial- and small-medium-scale sago agro-industry. Results: The results show that the supply chain sustainability performance on the industrial scale is 44.25, while it is 48.81 for the small-medium scale with the same status, almost sustainable. Key indicators for improving sago agro-industry supply chain sustainability performance include profit distribution among supply chain actors, institutional support for supply chains, waste utilization (reuse & recycle), and the availability of waste management facilities. The implication of this research for managers regards assessing the current status of sustainability performance and key indicators as a reference for formulating sustainability strategies and practices. Conclusions: The results of the study will enable supply chain actors to understand the key indicators for improving sustainability performance in the sago agro-industry supply chain, especially in Meranti Islands Regency, Riau Province. The proposed model can be applied to other agro-industries by adjusting the indicators used and assessing data availability and suitability for the research object.",
"keywords": [
"ANFIS models",
"Fuzzy Inference System",
"sago agro-industry",
"sustainable supply chain",
"sustainability performance"
],
"content": "Introduction\n\nThe Rio Process instituted sustainable development for the first time at the 1992 Earth Summit in Rio de Janeiro (United Nations, 1992). The United Nations General Assembly adopted the Sustainable Development Goals (SDGs) in 2015 (for 2015 to 2030). The Rio Process explains how they are integrated and inseparable from achieving sustainable development at the global level (Purvis et al., 2019). In various fields, such as manufacturing, agriculture, and transportation, there has been growing recognition of the need to adopt sustainable practices. Supply chains are especially important as they impact the entire life cycle of products, from the sourcing of raw materials to the disposal of waste. Supply chains need to prioritize sustainable practices in order to minimize their impact on the planet and ensure a better future for all. A sustainable supply chain is one in which materials, information, and capital work together among stakeholders along the supply chain to achieve the target value of economic, social, and environmental dimensions in response to consumer and other stakeholder demands (Seuring and Müller, 2008). Carter dan Rogers (2008) defines a sustainable supply chain as the strategic, transparent integration and achievement of social, environmental, and economic organizations. Systemic business process coordination between critical organizations aims to improve the long-term financial performance of individual companies’ supply chains.\n\nThe concept of sustainable supply chain management (SSCM) is relevant to the sago agro-industry, as it aims to effectively manage the flow of materials, information, and money related to the procurement, production, and distribution of products or services to meet profit and business sustainability (Dubey et al., 2017). A sustainable supply chain model, which is designed to increase the competitiveness of all supply chain stakeholders (Sopadang et al., 2017), can be driven by legal compliance, competitive advantage, cost reduction, economic performance, innovation, social and environmental responsibility, risk management, corporate reputation, quality management, managerial attitude, top management support, team member motivation, government policies, competitors, customers, collaboration with suppliers, pressure from investors, and the influence of NGOs (Emamisaleh and Rahmani, 2017; Engert et al., 2016; Tay et al., 2015). Although sustainable supply chain management is a voluntary effort, business entities cannot ignore the existence of both internal and external incentives. In the case of the sago agro-industry, the supply chain sustainability must be assessed to determine its current performance status and identify tactical steps for supply chain actors to improve supply chain sustainability (Hafezi et al., 2017). This is strategic and essential to supporting food and energy security, as sago palm has huge potential as a source of staple food with little or no competition for fertile land from other food crops, and also for industrial raw materials and renewable energy sources (Ehara et al., 2018). Therefore, sustainable supply chain management can help to ensure the long-term viability and competitiveness of the sago agro-industry.\n\nThe sago agro-industry in Indonesia varies from small to large industries. Small industries start with sago farmers who also process sago stalks into sago starch slurry, which medium or large industries will process further. In addition to obtaining raw materials in the form of wet sago starch from processing farmers or small enterprises, large industries also process sago stalks from farmers or traders and their gardens. This condition describes the complex supply chain of the sago agro-industry. Supply chain sustainability assessment involves a multi-dimensional, multi-criterion, and dynamic process. The method chosen for assessing the level of sustainability must accommodate quantitative and qualitative data, the presence of uncertainty, inaccurate and incomplete data, unclear assessments, and characteristics of human evaluation. For this reason, a sustainability assessment model for the supply chain is needed.\n\nA comprehensive supply chain assessment necessitates the use of multiple sources of data. However, information sources have several limitations, including uncertainty, insufficient information, a lack of knowledge on the part of decision makers, and the inability of experts to produce appropriate evaluations (Bappy et al., 2019). In previous research, the number of sustainability indicators was still inaccurate, and the numbers dominated qualitatively. Sustainability assessment also requires qualitative and quantitative indicators to synthesize the opinions of several experts to make the evaluation more comprehensive. The method widely used to assess multi-dimensional sustainability does not accommodate expert opinion, focusing only on output efficiency. The multidimensional scaling (MDS) method has several weaknesses, including the potential to give the wrong indicator score, high subjectivity, the impact of the assessor’s imperfect knowledge on the score, and a scale that requires many objects of comparison for the assessment.\n\nMeanwhile, fuzzy set theory (FST) has an excellent opportunity to be implemented as a basic model in developing a framework for assessing the sustainability of agro-industry supply chains. This model accommodates qualitative and quantitative sustainability indicators that can be completed and combined. Other advantages of FST for evaluating sustainability include adapting to uncertainty, inaccurate and incomplete data, the ambiguity of assessment, and the characteristics of human judgment. In addition, experts and the human mindset readily accept the fuzzy sustainability assessment model. Hence, the evaluation becomes more effective (Houshyar et al., 2014).\n\nThis research aims to design a sustainability assessment model for the sago agro-industry supply chain and identify critical indicators for improving sustainability. The study was conducted on the sago agro-industry in the Meranti Islands Regency, Riau Province, Indonesia, through observation and interviews. The sustainability indicators are selected on the basis of a review of the literature and expert validation. Sustainability assessment of the economic, social, and environmental dimensions is carried out with the fuzzy inference system (FIS). After the sustainability value of each size is obtained, it is used for the overall sustainability value aggregation using adaptive neuro-fuzzy inference system (ANFIS). The results of the analysis will determine critical sustainability indicators in the sago agro-industry supply chain.\n\n\nMethods\n\nThe research framework is divided into four stages: identification of sustainability indicators, FIS modelling, ANFIS modelling, and analysis of critical indicators. The FIS model was created to evaluate the performance of each dimension. The ANFIS model, on the other hand, was used to combine the value of each dimension into the overall supply chain sustainability performance. Figure 1 depicts the research framework.\n\nThe research begins with identifying indicators in each dimension, followed by the development of the FIS model to assess the sustainability performance of each dimension, and finally, the aggregation of the sustainability performance of each dimension with the ANFIS model. Furthermore, critical indicators for increasing the supply chain sustainability of the sago agro-industry were analyzed. The stages of the research are shown in Figure 2. The steps of the study are as follows:\n\nIdentification of sustainability indicators\n\nThe first stage of this study is to identify sustainability indicators in the case study on the sago agro-industry. Field observations and a literature review were used to identify sustainability indicators, which were validated through in-depth interviews with practitioners and experts. The indicators that have been selected had to undergo the validation process and critique from relevant experts and stakeholders (Waas et al., 2014). Indicators in each dimension are needed to assess the sustainability level of each dimension. The indicator value of each dimension can be in the form of qualitative or quantitative data.\n\nSustainability indicators describe and provide information on the sustainability achievements of an organization in each dimension (Juwana et al., 2012). Indicators chosen to assess supply chain sustainability can be viewed from several perspectives, such as environmental impact, social responsibility, and economic feasibility, and must reflect the performance level of the defined sustainability dimensions (Nijkamp and Vreeker, 2000; Waas et al., 2014). Sustainability indicators must be supported by qualitative or quantitative data (Galal and Moneim, 2016; Popovic et al., 2018).\n\nSustainability assessment with FIS model\n\nA FIS is a system that is applied to regulate the relationship between the input and output variables of a system. FIS are classified into three types: Mamdani, Sugeno, and Tsukamoto (Castillo et al., 2007). The primary distinction between Mamdani and Sugeno is the outcome of fuzzy rules. As a result of the rule, the Mamdani type employs a fuzzy set, whereas the Sugeno type employs a linear function. The result of each fuzzy rule for the Tsukamoto type employs a monotonic membership function. The Mamdani type was used in this study.\n\nThe FIS uses a fuzzification interface to convert crisp input into fuzzy input. After fuzzification, a rule base is developed. Knowledge basis and rule base are interchangeable terms. Finally, defuzzification is used to convert the fuzzy value into the crisp value of the output.\n\nThe FIS model’s fuzzification stage represents sustainability indicator data for each dimension. Concerning the target of each indicator, all indicators are scaled with five linguistic levels: very low (VL), low (L), moderate (M), high (H), and very high (VH). If the target is minimal, the linguistic scale will be reversed; very high (VH) will start at the lowest value.\n\nUsing a specific membership function, the fuzzification stage converts observed data into fuzzy integers. The membership function in this study is a triangular fuzzy number (TFN). FIS rules are organized in the membership function based on the number of inputs and linguistic levels to produce consequences or outputs. The rule number for each dimension is calculated by multiplying the linguistic levels in the membership function (m) by the number of indicators (n), as specified in Equation 1. Each sustainability dimension has five indicators, and each indicator has five linguistic levels in the membership function, so 3125 rules on economic, social, and environmental aspects must be written for each FIS model.\n\nThe operator “AND” is associated with the FIS model’s input variables. The FIS model used the Mamdani model, and the output was represented by a linguistic label. Linguistic labels for sustainability performance are classified into five levels: very unsustainable, unsustainable, almost sustainable, sustainable, and very sustainable. To establish the proper output of the fuzzy rule, experts validate the reflection of the relationship of input variables. This study employs approaches proposed by Phillis et al. (2011) to generate output on the fuzzy rules basis.\n\nThe fuzzy set with the linguistic scale is assigned an integer value of 1, 2… so on, where one corresponds to the fuzzy set with the lowest sustainability. The fuzzy set VL is assigned a value of 1, L a value of 2, M a value of 3, H a value of 4, and VH a value of 5. Furthermore, each input combination in each rule is summed to get the output value (OV), which is grouped into five linguistic scales.\n\nThree thousand one hundred twenty-five rules represented the sustainability dimensions. For example, for rule number 2,675, social sustainability is sustainable if (institutional support is very high) and (local labor absorption is low) and (infrastructure to support activities is low) and (workers’ welfare is very high) and (participation of farmers in partnership is very high). The result is as follows:\n\nThe FIS model for this study employs the implication method “min” and the aggregation method “max” to evaluate the performance of the sustainability dimension. The method of centroid defuzzification is used. The parameters used to generate the FIS model to evaluate the performance of the sustainability dimension are summarized in Table 1.\n\nAggregation of sustainability performance with the ANFIS model\n\nThe FIS and Artificial Neural Networks (ANN) learning benefits are combined in ANFIS. Despite system uncertainty, the FIS rule base describes the relationship between output and input parameters. ANN trains data and finds the best settings for the FIS membership function to get fuzzy rules and membership functions accordingly (Tozan and Vayvay, 2008). ANFIS is a simple data learning technique that converts given inputs into target outputs using a FIS model. Fuzzification, product, normalization, defuzzification, and total output are the five primary process stages in ANFIS operations (Paul et al., 2015). The ANFIS model is structured similarly to the FIS model, except for estimating the membership function parameters and the FIS rules (Abdel-Aleem et al., 2017).\n\nSeveral factors must be considered when developing the ANFIS model, including the variable input membership function, the number of training data pairs, epochs, and the model’s error tolerance. In ANFIS modelling, the membership functions (MFs) use grid partitioning by five linguistic MFs (very low, low, medium, high, and very high). Gaussian MFs were used in this model because they accurately describe the data distribution of a real-world problem (Moghaddamnia et al., 2009). The ANFIS learning algorithm combines the least squares estimator (LSE) and error backpropagation (EBP) methods. The model was trained for 10,000 epochs with zero error tolerance. A suitable ANFIS model should have a < 0.1 error (Sun et al., 2015). The parameters used to develop the ANFIS model for aggregating the sustainability supply chain of the sago agro-industry are listed in Table 2.\n\nAnalysis of key indicators\n\nThe key indicators should be determined to design a strategic program to increase or maintain supply chain sustainability. Critical indicators are analyzed with the cosine amplitude method (CAM) at this stage. CAM is recommended because it effectively synthesizes fuzzy indicator measures (Ross, 2010). CAM looks for the similarity of data i and data j, symbolized by rij. Data i and j are n data, each having a membership function m in the fuzzy membership function. Each element of a relationship rij is the result of a pairwise comparison of two data samples, say xi and xj, where the membership value expresses the strength of the relationship between xi and xj is given. The relation matrix will be of size n × n and, as with all similarity relations, will be reflexive and symmetric — thus, a tolerance relation. The score of the similarity between data i and j (rij) is formulated using Equation 2 and, like all similarity methods, guarantees that 0 ≤ rij≤ 1 (Ross, 2010).\n\nNext, the value of rij is arranged into a matrix, and then the average value is searched and normalized to determine the sensitivity value of each indicator. Finally, the value of the key indicators of each sustainability dimension can be determined.\n\nSpecific sustainability indicators assess supply chain sustainability in the sago agro-industry. This study used 15 indicators with three sustainability dimensions, grouped as qualitative and quantitative data and analyzed using the formula in Table 3. Quantitative data on sustainability indicators were obtained through field surveys, in-depth interviews with supply chain actors, and previous research. Qualitative data was obtained by expert assessment and in-depth interviews with supply chain actors. Supply chain and sago sustainability experts include business actors, academics, and researchers.\n\nThis study generated 1,000 data sets using random numbers from zero to 100 by considering all the rules for the input-output relationship to develop the ANFIS model because of the limited availability of actual data. Seven hundred pairs were used for data training, and 300 pairs were used for data testing.\n\nThis study’s verification and validation model refers to Sargent (2013). The validation procedure ensured the accuracy of the formula and the model. At this point, literature studies back up the FIS model’s sustainability indicators. FIS and ANFIS model verification ensures the model has the lowest possible error. Experts with knowledge of the model and current real-world conditions perform validation of conceptual models.\n\nThe conceptual model is validated by guaranteeing that literature studies justify the sustainability indicators. Fifteen sustainability indicators are used to assess supply chain sustainability performance. All sustainability indicators were determined using field surveys, expert opinions, interviews, and literature reviews. Table 4 shows evidence of verification of sustainability indicators based on a literature review.\n\nFIS and ANFIS model verification is done by evaluating the performance of FIS and ANFIS modelling. The evaluation of the FIS and ANFIS models uses RMSE, the number of membership functions, rules, and error values in training and testing.\n\nThe evaluation of the ANFIS model was carried out using RMSE, which is one of the most popular metrics for evaluating continuous error models. RMSE is a calculation made to find the minor error from the following parameters in the forward step, fix the value of the premise parameter in the backward step with error propagation, and then calculate the error output from the network (Fatkhurrozi et al., 2012). As the name suggests, RMSE is the square root of the mean squared error. RMSE is described in Equation 3 below. xi is the prediction value i to n, yi represents the observed value i to n, and n is the number of the data.\n\n\nResults and Discussion\n\nThe goal of any supply chain is to maximize profits from the overall supply chain activity (Chopra and Meindl, 2013). A measure of supply chain success is how thriving activities are coordinated across supply chain levels to create value for consumers and increase profits for each actor in the supply chain (Somashekhar et al., 2014). The supply chain structure describes the boundaries of the supply chain network and represents the prominent members of the supply chain and the roles of each member. In addition, the supply chain structure also explains all the configurations and institutional arrangements or elements in the supply chain that form the network and encourage various business processes. In this research, the supply chain network boundary of the sago agro-industry consists of suppliers, manufacturers, and distributors, which are depicted in the supply chain structure in Figure 3.\n\nIndustrial-scale sago agro-industry uses three sources of raw material: sago trunks from sago farmers or traders, sago trunks from factory gardens, and wet sago starch from small-scale wet sago mills. Meanwhile, the small-medium-scale sago agro-industry obtains raw materials only from sago farmers. Distributors will distribute sago starch to retailers or downstream industries.\n\nThe sustainability of the sago agro-industry supply chain is assessed on three dimensions: economic, social, and environmental. Fifteen indicators have been selected to assess economic, social, and environmental sustainability based on a literature review, in-depth interviews, and expert validation (Table 4).\n\nTable 5 shows the target, maximum, and minimum indicator values for evaluating the supply chain sustainability performance of the sago agro-industry. The proposed model is built with quantitative and qualitative data (Galal and Moneim, 2016; Popovic et al., 2018). Observations, interviews, and measurements were used to collect quantitative data, while expert judgment and a fuzzy membership function were used to collect qualitative data. Qualitative indicators are those that have linguistic labels.\n\nWith five indicators as inputs, the FIS model is used to assess the performance of each dimension of sustainability. Using FIS, three models were developed for assessing the economic, social, and environmental dimensions of sustainability. Because each dimension has five indicators, 3,125 rules (55 in total) must be created to determine the sustainability performance of every dimension. Figure 4 depicts the fuzzy membership function of the FIS model’s input-output to determine the sustainability performance of the economic dimension.\n\na) membership function of input 1. b) membership function of input 2. c) membership function of input 3. d) membership function of input 4. e) membership function of input 5. f) membership function of output.\n\nThe consequences of fuzzy rules in this study refer to the methodology proposed by Phillis et al. (2011). Figure 5 depicts the FIS framework for assigning supply chain sustainability performance for the social dimension, while Figure 6 depicts the rule display surfaces. Here are some examples of rules for each of the dimensions generated by the FIS:\n\n1. If (supply chain risk is medium), (profit distribution is high), (raw material supply is very high), (demand is very high), and (market access is medium), then (economic sustainability is sustainable).\n\n2. If (institutional support is medium), (local labor is very high), (infrastructure support is high), (workers’ welfare is high), and (farmers’ partnership is very high), then (social sustainability is very sustainable).\n\n3. If (fuel consumption emissions are very high), (water consumption is high), (waste complaints are medium), (waste utilization is high), and (waste management facilities are very high), then (environmental sustainability is almost sustainable).\n\nThe Mamdani type with a TFN membership function and a centroid defuzzification function was used to build the FIS model. Experts carry out the validation of the rule base in the FIS model. Following the generation of the FIS model, the data in Table 5 are used to assess the sustainability of each dimension in the industrial- and small-medium-scale sago agro-industry. In the economic, social, and environmental dimensions, the value of the sustainability of the industrial-scale sago agro-industry supply chain was 37.74, 55.29, and 53.17, respectively. Meanwhile, the economic, social, and environmental values of the sustainability of the small- and medium-scale sago agro-industry supply chain were 56.61, 50, and 24.88, respectively. Figure 7 depicts the economic, social, and environmental sustainability of industrial- and small-medium-scale sago agro-industry supply chains.\n\nYusuf et al. (2019) assessed the sustainability of the sago agro-industry in South Sorong, Papua using the MDS technique with five dimensions and 25 indicators. The difference in indicators used, analytical methods, and research locations will, of course, result in different sustainability performances, so the results of this study cannot be compared. However, the similarity between this study and previous studies is that the value of the environmental dimension is lower than that of the economic and social dimensions. Previous research using the FIS model to assess supply chain sustainability has been carried out by Yani et al. (2022) in the sugarcane agro-industry with four dimensions and 24 indicators.\n\nOn the industrial scale, the lowest value is in the economic dimension, while on the small and medium scale, it is in the environmental dimension. The economic dimension indicators with the lowest value for the industrial scale are fair profit distribution among supply chain actors, a sufficient supply of raw materials to meet capacity, and a marketing network. The environmental dimension indicators with the lowest value for the small-medium scale are waste utilization and availability of waste management facilities.\n\nSupply chain risk and fair distribution of profit among supply chain actors are critical indicators for improving the sustainability performance of the sago agro-industry supply chain, on both an industrial and a small-medium scale. Some literature states that agro-industry performance can be improved by efficient supply chain risk management (Safriyana et al., 2019; Septiani et al., 2016; Suripto et al., 2018; Zainuddin et al., 2017). Supply chain risk management uses strategies, techniques, and tools to manage risk along the supply chain to achieve sustainability through collaboration between supply chain members (Mulyati and Geldermann, 2017). One approach to optimizing supply chain risk and mitigation is acceptable risk and balanced profit distribution from the supply chain. It is important to acknowledge the significance of this approach in situations of uncertainty, particularly when working with multiple stakeholders, and to take into account the effects of past collaborative decision-making efforts. As a result, a fair and balanced risk and profit approach seeks to achieve a win-win solution by sharing and distributing profit and risk among all stakeholders to optimize supply chain performance (Chen, 2015; Palsule-Desai, 2013; Qian et al., 2013).\n\nImportant indicators in the social dimension are the participation of farmers in partnership and institutional support in both the industrial- and small-medium-scale sago agro-industry supply chains. Cooperation with suppliers has a positive impact on company performance. By reducing transaction costs and obtaining valuable technical resources, a comparative advantage in performance can be achieved through collaboration with suppliers (Wang and Dai, 2018). Previous researchers have mentioned institutional advantages for supply chains. Astuti et al. (2010) stated that the effectiveness and efficiency of the supply chain in achieving its goals are increased through the identification of needs and institutional structures in the supply chain. Institutions have a significant relationship with two elements, namely, information sharing and collaborative planning, which can increase profits and reduce transaction costs along the supply chain (Kalyar et al., 2013). Institutional is an effort to design interaction patterns so that they can carry out transactions between economic actors and various institutions, such as banks and governments (Alkadafi, 2014). The absence of institutions significantly impacts supply chain performance (Silvestre, 2015). Sustainable performance mitigates the consequences of the collaboration barriers required to establish sustainable supply chain productivity (Kumar and Goswami, 2019).\n\nImportant indicators in the environmental dimension are complaints about agro-industrial waste, waste utilization, and availability of waste management facilities. The complaints about agro-industrial waste indicator has the highest value of all the indicators in the environmental dimension. However, the availability of waste management facilities is deficient and even non-existent in the small-medium-scale sago agro-industry. The community around the sago agro-industry that probably causes this are workers who depend on the sago agro-industry for their income. Some are concerned about waste and losing their source of income if the sago factory is closed.\n\nProcessing sago palms into sago starch requires water to extract the starch. The processing will produce both liquid and solid waste. Sago stalks are washed, hulled, and grated before being milled or processed for pulping during the sago starch extraction process. A large amount of water is discharged as sago waste during the manufacturing process. The waste is rich in carbohydrates, fiber, suspended solids, unextracted starch, cellulose (fibrous residue from pith), nitrogen compounds, cyano-glucosides, and insoluble fiber. It contains high concentrations of organic matter (such as proteins, lipids, and carbohydrates), is acidic, and emits a foul odor that causes pollution and worsens global environmental quality (Wee et al., 2017). The sago agro-industry, both industrial- and small-medium-scale, must pay attention to indicators L4 and L5 because the content of this waste can worsen environmental quality even though there are no complaints from the community about it.\n\nAggregate values must reflect the total supply chain sustainability performance derived from the sustainability performance of the dimension of the previous stage. The ANFIS technique aggregates sustainability performance for each measurement, with three parameters as input: economic, social, and environmental dimensions. The model’s output is the supply chain sustainability of the sago agro-industry. The ANFIS model with grid partition initiation was developed for this study to determine supply chain sustainability performance. The ANFIS model is structured using Gaussian MFs and three input variables, each with five MF levels, resulting in 125 rules that produce one output as the supply chain sustainability performance. The learning process uses 700 data sets and 300 data sets for testing. The data set was trained using a hybrid learning algorithm with 10000 epochs. It can be seen in Figure 8 that the error value significantly decreased at the 0-4000th epoch and resulted in the smallest error value at the 8300th epoch with a value of 0.007267. Table 6 shows a summary of the parameters and factors considered for developing the ANFIS model for the aggregation of the overall supply chain sustainability performance of the sago agro-industry.\n\nANFIS training is critical for creating a model and determining the parameters with the least error. The ANFIS model’s training data have an error of 0.007267, while the test data have an error of 0.009306. The error condition for model training is < 0.1 (Sun et al., 2015). RMSE was also used to test the ANFIS model. With an RMSE value of 0.009592, the RMSE parameters for ANFIS performance evaluation show that the ANFIS model performs well. The RMSE value of 0.009592 indicates that the average predicted value differs from the actual value by 0.009592. Based on the performance evaluation, the ANFIS model can accommodate the aggregation of the supply chain sustainability of the sago-agro-industry.\n\nFigure 9 depicts the ANFIS model’s MFs following the training process. The MFs scale changes dynamically at each linguistic level, indicating that the model accurately reflects the training data. Figure 9 demonstrates the importance of training data in configuring MFs to predict the output. As a result, compared to the previously mentioned ANFIS model, the ANFIS model with grid partition can aggregate overall supply chain sustainability performance with near-zero errors.\n\nANFIS successfully designed three input dimensions of sustainability and one output from aggregating the total supply chain sustainability performance by launching the grid partition model. Figure 10 depicts the ANFIS model’s architecture. Finally, the ANFIS model is used to aggregate the overall sustainability performance of the supply chain. This study validates the performance of the sustainability dimension by aggregating the overall supply chain sustainability performance using the ANFIS model. The validation results show that the industrial-scale sago agro-industry supply chain sustainability performance is 44.25, while the small-medium-scale sago agro-industry is 48.81. Both companies’ supply chains are in the almost sustainable category. Verification of the ANFIS model is performed to aggregate the overall supply chain sustainability performance using an error value.\n\nThe ANFIS model has also been used to assess country sustainability (Nilashi et al., 2018; Tan et al., 2017). The number of inputs, data sets, membership functions, and epochs strongly influences the lowest error value achieved in the training process.\n\nThe advantage of the sustainability performance assessment model using the FIS and ANFIS techniques is that it can be used repeatedly to assess sustainability performance regularly by ensuring that indicators and ranges of values are still relevant. Managers must measure sustainability performance periodically to develop an action plan (Sharma et al., 2021).\n\nKey indicators are analyzed using the CAM approach to determine which ones can significantly improve sustainability performance. Key indicators need to be sought for each dimension of sustainability, economic, social, and environmental. CAM shows that indicators with high values are key indicators that should be used to improve sustainability performance.\n\nThe critical indicators in industrial- and small-medium-scale sago agro-industry supply chains are slightly different. The key indicators of the economic dimension in the industrial-scale sago agro-industry supply chain include fair distribution of profit among supply chain actors (E2), differences in product demand (E4), and market access/marketing networks (E5). In the small-medium scale, they are E4, supply chain risk (E1), and E5. The critical indicator E2 is in line with previous research on the supply chain of the coffee, cocoa, and sugarcane agro-industry, which states that fair profit sharing, is the primary indicator of the economic dimension (Jaya et al., 2013; Sriwana et al., 2017; Yani et al., 2022). Figure 11 presents the key indicators of the economic dimension in the supply chain of the industrial- and small-medium-scale sago agro-industry.\n\nThe key indicators of the social dimension in the industrial-scale sago agro-industry supply chain include the availability of infrastructure to support activities (S3), institutional support for supply chains (S1), and workers’ welfare (S4). In the small-medium-scale industry, they are S4, S3, and S1. Although the values and order of the key indicators in the industrial scale and the small-medium scale are different, the key indicators of the social dimension in both industrial scales are the same, namely, S1, S3, and S4. The S1 indicators need to be improved, considering their shallow values may not even exist to improve the sustainability performance of the sago agro-industry supply chain. The critical indicator S1 is in line with previous research on the cocoa and sugarcane agro-industry supply chain, which states that institutional support is the primary indicator of the social dimension (Sriwana et al., 2017; Yani et al., 2022). Figure 12 shows critical indicators of the social dimension in the supply chain of the industrial- and small-medium-scale sago agro-industry.\n\nThe key indicators of the environmental dimension in the industrial-scale sago agro-industry supply chain are fuel consumption emissions (L1), availability of waste management facilities (L5), and water consumption (L2). In the small-medium scale, they are L2, waste utilization (reuse & recycle) (L4), and L1. All indicators used to assess the sustainability of the environmental dimension are critical. The indicators that still need to be improved by the two scales of the sago industry are L4 and L5, which are currently very minimal and have not even been carried out in the small-medium scale sago agro-industry. Previous research on the coffee and sugarcane agro-industries supply chain has also stated that it is a significant indicator of the environmental dimension and needs more attention (Jaya et al., 2013; Yani et al., 2022). Figure 13 shows the critical indicators of ecological measurements in the supply chain of the industrial- and small-medium-scale sago agro-industry.\n\nThe results of the analysis of key indicators are the critical indicators that, if the value is increased, will significantly improve sustainability performance. Analysis of these key indicators is needed to formulate strategic and action plans to improve sustainability performance. Key indicators for improving sustainability performance in each dimension include fair profit distribution among supply chain actors, institutional support for supply chains, waste utilization (reuse & recycle), and availability of waste management facilities.\n\nThe sustainability performance assessment model for the sago agro-industry was developed using carefully chosen indicators that are relevant to the industry. The sustainability of the sago agro-industry supply chain must be carried out jointly by all actors in the supply chain. To find out the sustainability status, managers at focused companies can periodically assess the sustainability performance of the supply chain. The advantage of the sustainability performance assessment model using FIS and ANFIS is that it can be used frequently and updated regularly. Identifying critical indicators helps managers develop strategic plans and practices to improve sustainability performance.\n\n\nConclusions\n\nBased on FIS and ANFIS, this study develops a two-stage sustainability assessment model for the sago agro-industry supply chain. The proposed sustainability assessment model is accurate and can be used based on model verification and validation results. The developed FIS model can evaluate the supply chain sustainability performance of the industrial- and small-medium-scale sago agro-industry in all dimensions. The supply chain sustainability performances in the economic, social, and environmental dimensions of the industrial-scale sago agro-industry are 37.74 (unsustainable), 55.29 (almost sustainable), and 53.17 (almost sustainable), respectively. In the small-medium scale, the scores are 56.61 (almost sustainable), 50 (almost sustainable), and 24.88 (unsustainable), respectively.\n\nANFIS model has grid partition initiation that incorporates supply chain sustainability performance across all dimensions. The ANFIS model has close to zero training and testing errors, implying that it was able to assess supply chain sustainability performance with good results. The validation process reveals that the supply chain sustainability performance of the sago agro-industry is 44.25 in the industrial-scale industry and 48.81 in the small-medium scale, with a sustainability status of almost sustainable. In addition, key indicators for enhancing supply chain sustainability performance are examined in this study. Key indicators for improving the sustainability performance of the sago agro-industry supply chain include profit distribution among supply chain actors, institutional support for supply chains, waste utilization (reuse & recycle), and the availability of waste management facilities.\n\nThe model presented in this study for assessing the sustainability of the sago agro-industry supply chain is limited to three dimensions: economic, social, and environmental. Further research may add other dimensions, such as resources or technology. Considering data availability, only five indicators are used in each dimension. The proposed model can be applied to other agro-industries by adjusting the indicators used and assessing data availability and suitability for the research object.\n\nFair profit distribution among supply chain actors is the key indicator of the economic dimension, and further research on the proper profit distribution model is needed. In addition, research on institutional strengthening of the sago agro-industry supply chain is also required to accommodate the critical indicators in the social dimension. Finally, it is also important to formulate a strategy for waste management (reuse & recycle) and identify the facilities that are needed by considering the environmental impacts and costs involved.\n\n\nEthical statement\n\nThis study has been approved by The Head of Agroindustrial Engineering Postgraduate Program at Bogor Agricultural University, under the approval number: 770/IT3.6.3/KM/M/B/2023. Informed written consent was collected from each participant.",
"appendix": "Data availability\n\nThis data consists of two data sets to create a sustainability assessment model and analysis code written in GNU Octave:\n\nFigshare. Data set ANFIS model for sustainability performance assessment of sago industry supply chain. https://doi.org/10.6084/m9.figshare.22141334 (Yusmiati, 2023a)\n\nThis project contains the following underlying data:\n\n1. Dataset for train ANFIS model.csv (Data set for model learning)\n\n2. Dataset for test ANFIS model.csv (Data set for model testing)\n\n3. Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare. Sustainability supply chain analysis code written in GNU Octave version 8.1.0. https://doi.org/10.6084/m9.figshare.22620538 (Yusmiati, 2023b)\n\n1. Economic_dimension.m (Analysis code for economic dimension)\n\n2. Social_dimension.m (Analysis code for social dimension)\n\n3. Environmental_dimension.m (Analysis code for environmental dimension)\n\n4. Aggregation.m (Analysis code for aggregation)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgments\n\nThanks to the National Research and Innovation Agency of the Republic of Indonesia for the Saintek Scholarship program. We also thank the reviewers who have provided suggestions for improving the final version of this article.\n\n\nReferences\n\nAbdel-Aleem A, El-Sharief MA, Hassan MA, et al.: Implementation of fuzzy and adaptive neuro-fuzzy inference systems in optimization of production inventory problem. Appl. Math. Inf. Sci. 2017; 11(1): 289–298. Publisher Full Text\n\nAlkadafi M: Penguatan ekonomi masyarakat melalui pengelolaan kelembagaan badan usaha milik desa menuju ASEAN economic community 2015. Journal El-Riyasah. 2014; 5(1): 32–40. 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}
|
[
{
"id": "216520",
"date": "06 Nov 2023",
"name": "Stefania Tomasiello",
"expertise": [
"Reviewer Expertise Machine learning/soft computing"
],
"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 level of novelty is quite limited. The presentation and organization of the paper are messy and this makes it difficult to read.\n\nThe approach is not original, but it follows the one presented by Yani et al (2022). The authors cited this work, but they failed to clarify that they are following the same approach applying it to a different case study.\n\nA recent relevant work should also be cited: Data‑driven approaches for sustainable agri‑food: coping with sustainability and interpretability, Journal of Ambient Intelligence and Humanized Computing https://doi.org/10.1007/s12652-023-04702-w\n\nIn Figure 2, \"sets data\" should be \"sample data\".\n\nEq. (1) should appear as soon as it is recalled before the statement \"Each sustainability dimension has five indicators...\"\n\nOn page 6, the statement \"The fuzzy set VL is assigned a value of 1, L a value of 2, a value of 3, H a value of 4, and\nVH a value of 5.\" should be rewritten in a better way. First of all, VL, L etc are acronyms for linguistic variables that should be recalled with their full names, I mean the acronyms should be introduced in brackets. Secondly, what does it mean that they are assigned a single value? Fuzzy sets are not crisp variables.\n\nSome preliminaries to introduce the basic notion of fuzzy sets are missing.\n\nRegarding the FISs the list of adopted linguistic variables, with their term set (including the kind of membership function), should appear in the first section where the authors introduce the FIS, i.e. starting with page 6, not on page 11, after they have introduced ANFIS and other stuff.\n\nAfter the introduction and a related works section (which is missing), I advise having a section devoted to preliminaries where whatever is useful to introduce the approach is presented, then a section for the approach and a section for the numerical results and discussion about them, before the conclusions.\n\nIt is unclear the reason why one should first use some FISs and then ANFIS. The inputs to the FISs could be given directly to ANFIS. A recent variant of ANFIS allows for very good accuracy, even for a large number of variables: https://ieeexplore.ieee.org/document/9732219\n\nFigures reproducing tool windows, such as Fig. 8, should be avoided. Only the graph should be shown.\n\nThe authors claimed \"This study generated 1,000 data sets using random numbers from zero to 100\". How can they assume that this will produce reliable results in a real-world scenario?\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "12389",
"date": "29 Oct 2024",
"name": "Yusmiati Yusmiati",
"role": "Author Response",
"response": "The approach is not original, but it follows the one presented by Yani et al (2022). The authors cited this work, but they failed to clarify that they are following the same approach applying it to a different case study Thank you for your feedback. We acknowledge that the approach presented in our article may not be entirely original, as it is based on the one presented by Yani et al (2022). We apologize for not clarifying that we are following the same approach and applying it to a different case study in the sustainability performance assessment of the sago industry supply chain. We make sure to address this issue in our revised manuscript in the first paragraph in Methods section. “We employ a study methodology similar to that of Yani et al. (2022) to evaluate sustainability in the supply chain of the sugar agro-industry by varying the indicators in each dimension according to our research subjects, which serves to indicate the sustainability level.” A recent relevant work should also be cited: Data driven approaches for sustainable agri food: coping with sustainability and interpretability, Journal of Ambient Intelligence and Humanized Computing https://doi.org/10.1007/s12652-023-04702-w It has been cited. “Apart from its advantages, the ANFIS ensemble certainly also has weaknesses, namely the large computational process and energy consumption (Tomasiello et al., 2023).” In Figure 2, \"sets data\" should be \"sample data\" Has been corrected according to the reviewer’s instructions Eq. (1) should appear as soon as it is recalled before the statement \"Each sustainability dimension has five indicators...\" Has been corrected according to the reviewer’s instructions. On page 6, the statement \"The fuzzy set VL is assigned a value of 1, L a value of 2, a value of 3, H a value of 4, and VH a value of 5.\" should be rewritten in a better way. First of all, VL, L etc are acronyms for linguistic variables that should be recalled with their full names, I mean the acronyms should be introduced in brackets. Secondly, what does it mean that they are assigned a single value? Fuzzy sets are not crisp variables. These acronyms have been explained in Sub-point: Sustainability assessment with the FIS model, paragraph 3: ‘The fuzzification stage of the FIS model represents the sustainability indicator data for each dimension. Regarding the target of each indicator, all indicators are scaled with five linguistic levels: very low (VL), low (L), moderate (M), high (H), and very high (VH). If the target is minimal, the linguistic scale will be reversed; very high (VH) will start from the lowest value.’ I agree with you that Fuzzy sets are not crisp variables. The method I use by converting it to a crisp number is just to make it easier to scale the output in modelling. Some preliminaries to introduce the basic notion of fuzzy sets are missing Thank you for your feedback. We appreciate your comment on the missing preliminaries to introduce the basic notion of fuzzy sets in our article. We already revise and incorporate this important information to provide a clearer understanding of the topic for our readers in the Literature Review section, Fuzzy Inference System (FIS) sub section. Regarding the FISs the list of adopted linguistic variables, with their term set (including the kind of membership function), should appear in the first section where the authors introduce the FIS, i.e. starting with page 6, not on page 11, after they have introduced ANFIS and other stuff Thank you for your feedback on the placement of the list of adopted linguistic variables in our article. We appreciate your suggestion to include this information earlier. Our research uses the Triangular Fuzzy Number (TFN) membership function type, which has been explained after the explanation of linguistic variables in the sustainability assessment with the FIS model subsection. After the introduction and a related works section (which is missing), I advise having a section devoted to preliminaries where whatever is useful to introduce the approach is presented, then a section for the approach and a section for the numerical results and discussion about them, before the conclusions Thank you for your insightful feedback. We make sure to include a related works in literature review section after introduction. We introduce the approach in the literature review section and have added the steps in the ANFIS process to help readers unfamiliar with the method. Numerical results are presented in the result and discussion section, and the discussion has been presented before the conclusion. Your suggestions will greatly enhance the clarity and coherence of our article. It is unclear the reason why one should first use some FISs and then ANFIS. The inputs to the FISs could be given directly to ANFIS. A recent variant of ANFIS allows for very good accuracy, even for a large number of variables: https://ieeexplore.ieee.org/document/9732219 Thank you for your comment. The decision to first use FISs before ANFIS in our study was based on the complexity and nature of the data we were analyzing. However, we acknowledge the potential benefits of directly feeding the inputs to ANFIS. We will consider exploring the recent variant of ANFIS you provided in the link for future research. Thank you for your valuable input. Figures reproducing tool windows, such as Fig. 8, should be avoided. Only the graph should be shown Has been corrected according to the reviewer’s instructions. The authors claimed \"This study generated 1,000 data sets using random numbers from zero to 100\". How can they assume that this will produce reliable results in a real-world scenario? An explanation has been added to the section: The Overall Supply Chain Sustainability Performance, paragraph 2. “The production of 1000 data sets using random numbers ranging from zero to 100 prompts inquiries about the dependability of this method in real-world situations. Although the usage of random numbers is widespread in several domains, it is important to critically analyze the fundamental principles of randomness and how they affect the reliability of data in order to make accurate assumptions. The accuracy of generating random numbers is essential for ensuring the integrity of data. Pseudorandom number generators (PRNGs) produce random sequences using deterministic algorithms, which can lead to worries about their unpredictability and possible biases (Heese et al., 2021). While high-quality pseudorandom number generators (PRNGs) may be enough for machine learning tasks, any biases present in the PRNG can cause inconsistent outcomes in applications that require sensitivity (Aghamohammadi & Crutchfield, 2017). The effectiveness of random numbers is contingent upon the specific environment in which they are employed. Effective randomization techniques in clinical trials improve outcomes, however producing random numbers without taking into account the specific needs of the study can result in biased results (Pajcin et al., 2022). While constrained randomization enhances statistical features, the generation of random numbers does not ensure the creation of representative data sets (Peng et al., 2018).”"
}
]
},
{
"id": "180993",
"date": "14 Nov 2023",
"name": "Amir Karbassi Yazdi",
"expertise": [
"Reviewer Expertise Operations research",
"Fuzzy sets",
"MADM",
"SCM"
],
"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 of all, I would like to thank you very much for allowing me to evaluate this paper. After a major revision to this paper, it may be possible to index it.\nIt is very apparent that there is a gap in research, and it needs to be developed, and more explanations should be provided.\nResearch on the background of the issue needs to be included. The literature review has to be added to the paper, and some papers must be written about previous studies that have been conducted. As well as that, you might want to consider using some of the following papers:\nhttps://doi.org/10.1080/17509653.2022.2098543 https://doi.org/10.33889/IJMEMS.2022.7.1.008 https://doi.org/10.1504/IJLSM.2020.107386 https://doi.org/10.1080/09593969.2013.834836 https://doi.org/10.1155/2022/8221486 https://doi.org/10.1111/jiec.12440 https://doi.org/10.1080/12460125.2022.2090065\nThere needs to be more clarity regarding the contribution of this research.\nWhat was the reason for authors using ANFIS? Is there a reason why they didn't use another method?\nAn analysis that is sensitive to the results is required\nThe authors must include limitations and 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? 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": "12388",
"date": "29 Oct 2024",
"name": "Yusmiati Yusmiati",
"role": "Author Response",
"response": "1. Reviewer: Research on the background of the issue needs to be included. The literature review has to be added to the paper, and some papers must be written about previous studies that have been conducted. Author Response: Thank you for your feedback. We appreciate your suggestion to include research on the background of the issue and to enhance the literature review in our paper. We will make sure to add references to previous studies that have been conducted. We also consider using some of the papers you have recommended to further strengthen our argument and analysis. “Fuzzy inference systems (FIS) provide clear benefits over classical multicriteria decision-making (MCDM) methods, especially when it comes to managing the uncertainty and imprecision present in real-world decision-making situations (Yazdi et al., 2023). Recent studies have highlighted the effectiveness of fuzzy-based approaches in various applications, demonstrating their superiority in certain contexts (Yazdi et al., 2020) and also to deal with uncertain environments (Yazdi et al., 2022). Several curious studies have been conducted on agri-food supply chain management, one of which is about supplier selection desire by integrating fuzzy into the Analytic Network Process to assess selection criteria. The study emphasizes a comprehensive approach for supply chain managers suggesting an integrated decision support framework and recommends further exploration of criteria relationships and further MCDM techniques (Ada, 2022). Maximizing the total value of supply chain stakeholders is a future concern, and modeling is one of the promising techniques for addressing managerial decision-making issues (Gold et al., 2017). The capacity of fuzzy systems to control ambiguity in decision-making is one of its main advantages (Sarfaraz et al., 2023).” 2. Reviewer: There needs to be more clarity regarding the contribution of this research Author Response: It has been added according to the reviewer's suggestion in sub point: managerial implication paragraph 2. “The methodology this research provides can be used to other agro-industrial sectors that are confronting comparable sustainability issues, meaning that its ramifications reach beyond the sago business. The model's emphasis on multi-criteria evaluation and adaptability positions it as a valuable tool for practitioners and policymakers aiming to enhance sustainability performance across various supply chains.” 3. Reviewer: What was the reason for authors using ANFIS? Is there a reason why they didn't use another method? Author Response: The reason for selecting the method has been added in paragraphs 7-8 in the Literature Review section. “The ANFIS is becoming known as a powerful modeling tool due to its ability to integrate the benefits of fuzzy logic systems and neural networks. ANFIS is commonly used because it has the ability to accurately model nonlinear systems. Research has shown that when it comes to forecasting outcomes in fields like agriculture and medicine, ANFIS performs better than other machine learning approaches like Support Vector Machines (SVM) and K-Nearest Neighbors (KNN) (Gökkuş et al., 2022). The researchers in the field of agriculture employed ANFIS to precisely predict grain yields, showcasing its efficacy in comprehending the intricacies of agricultural data (Gökkuş et al., 2022). ANFIS has been utilized in medical applications to forecast significant adverse cardiovascular events, demonstrating its resilience in managing medical data that contains intrinsic uncertainties (Karsidani et al., 2022). ANFIS demonstrates exceptional effectiveness in situations that involve inaccurate or partial data. The design of this system enables it to successfully handle uncertainty, a common difficulty encountered in real-world applications (Ibrahim, 2024). ANFIS's versatility gives it an advantage over conventional statistical methods that may face difficulties in comparable circumstances. ANFIS has a notable advantage in its capacity to integrate human-like reasoning using fuzzy logic, resulting in improved interpretability of the model's judgments. This is especially advantageous in domains that need specialized expertise, such as environmental modeling and medical prognosis (Sulaiman et al., 2018). To summarize, ANFIS is preferred over other methods due to its precise modeling of nonlinear interactions, integration of human-like reasoning using fuzzy logic, better management of uncertainties, and improved performance through hybridization with optimization techniques.” 4. Reviewer: The authors must include limitations and future research Author Response: Has been added according to the reviewer's suggestion in the sub point: limitations and future research. “Three distinct dimensions—economic, social, and environmental—are the only ones included in the model this study suggests for assessing the sustainability of the supply chain for the sago agroindustry. Other study may incorporate other aspects, such as resources or technology. Due to limited data availability, only five indicators are utilized in each dimension. By changing the indicators and assessing the suitability and accessibility of the data for the study topic, the proposed model can be expanded to include a wider range of agro-industries. Equitable allocation of profits among participants in the supply chain is a crucial measure of the economic aspect, and additional investigation into the appropriate profit distribution model is required. Furthermore, it is necessary to do research on enhancing the institutional capacity of the sago agro-industry supply chain in order to address the crucial factors in the social aspect. It is crucial to develop a waste management strategy that includes reusing and recycling materials. Additionally, it is critical to determine the necessary facilities based on their environmental implications and associated costs.”"
}
]
},
{
"id": "191071",
"date": "14 Nov 2023",
"name": "Mukesh Kumar",
"expertise": [
"Reviewer Expertise Sustainable performance assessment"
],
"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 very much for writing the timely research article of sustainable performance assessment in Sago Industry by utilizing fuzzy interface model.\nYou need to justify why you use fuzzy interface system why not another MCDM technique.\n\nAuthors needs to add more recent articles from sustainable performance assessment using MCDM approach. I am providing you some of the recent articles on sustainable performance assessment. These are the research article that help you to modify your paper.\nhttps://doi.org/10.1016/j.jclepro.2018.06.015 https://doi.org/10.1016/j.jclepro.2022.133698 https://doi.org/10.1016/j.wasman.2021.05.013 https://doi.org/10.3390/su151511555\n\nIn the abstract section you need to please add Implication section.\n\nDiscuss your finding in detail.\n\nRewrite the Conclusion section\n\nplease proof check the whole manuscript\n\nplease match the citation and references\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": "12387",
"date": "29 Oct 2024",
"name": "Yusmiati Yusmiati",
"role": "Author Response",
"response": "You need to justify why you use fuzzy interface system why not another MCDM technique The reason for selecting the FIS has been added in the Literature Review section. “Fuzzy inference systems (FIS) provide clear benefits over classical multicriteria decision-making (MCDM) methods, especially when it comes to managing the uncertainty and imprecision present in real-world decision-making situations (Yazdi et al., 2023). Recent studies have highlighted the effectiveness of fuzzy-based approaches in various applications, demonstrating their superiority in certain contexts (Yazdi et al., 2020) and also to deal with uncertain environments (Yazdi et al., 2022). The capacity of fuzzy systems to control ambiguity in decision-making is one of its main advantages (Sarfaraz et al., 2023). Traditional MCDM methods often rely on crisp values, which can be inadequate when dealing with ambiguous or imprecise data. For instance, utilized fuzzy PROMETHEE to navigate the complexities of treatment options for COVID-19, showcasing how fuzzy logic can clarify decision-making in uncertain environments (Yildirim et al., 2021). This aligns with findings by, who noted that many real-world scenarios involve uncertainty that crisp evaluations fail to capture, thus necessitating the integration of fuzzy evaluations into MCDM frameworks (Hinduja & Pandey, 2023). Moreover, fuzzy systems enhance interpretability and flexibility in decision-making processes. The Fuzzy-ATOVIC method, for example, incorporates a FIS to improve the interpretability of the decision-making framework, allowing for a more nuanced understanding of the criteria and alternatives involved (Yusuf et al., 2022). This is particularly important in complex decision environments where stakeholders require clear justifications for choices made. In addition to interpretability, fuzzy MCDM methods have been shown to produce more consistent and reliable results. demonstrated that integrating fuzzy sets of interval type-2 with the Best-Worst Method (BWM) yielded faster and more reliable outcomes compared to traditional MCDM methods, which often require extensive pairwise comparisons (Öztürk et al., 2022). This efficiency is crucial in time-sensitive decision-making scenarios, such as supplier selection or resource allocation. Moreover, fuzzy MCDM approaches have been effectively used in a number of industries, such as manufacturing, civil engineering, and healthcare. For instance, a hybrid fuzzy MCDM approach was employed to optimize water supply planning, illustrating the versatility of fuzzy methods in addressing diverse decision-making challenges (Noori et al., 2020). Similar to this, fuzzy TOPSIS's usefulness in handling the intricacies of real-world decision-making was shown when it was applied to the supplier selection process for construction projects (Zaman & Mishra, 2023).” Authors needs to add more recent articles from sustainable performance assessment using MCDM approach. I am providing you some of the recent articles on sustainable performance assessment. These are the research article that help you to modify your paper. The citation of the article has been added as per the reviewer's suggestion. “Due to unsustainable practices, the growing demand for food has resulted in an increase in waste and environmental harm (Kumar et al., 2022a). Green supply chain management (GSCM), which emphasizes the integration of resource efficiency and environmental sustainability to improve performance across the supply chain, requires a thorough framework to evaluate performance. In addition, stakeholder collaboration is essential (Kazancoglu et al., 2018a). The sector must switch from a linear supply chain model to a circular one in order to maximize resource efficiency and minimize environmental effects. With this shift, the industry will receive socio-economic and environmental benefits (Lahane & Kant, 2021). The study by Kumar and Choubey (2023) highlights the significance of environmental variables and the necessity of routinely evaluating sustainability practices in order to ensure that they are in line with the SDGs. In the study, the multi-criteria fuzzy decision-making technique was applied.” In the abstract section you need to please add Implication section Has been corrected according to the reviewer’s instructions “Implication: The sago agro-industry sustainability performance evaluation methodology uses industry-relevant metrics to assess supply chain sustainability, promoting collaboration among stakeholders and assisting in the creation of sustainable strategies.” Discuss your finding in detail Already added to the sub point: discussion “The work by highlights the importance of utilizing a multi-criteria adaptive fuzzy inference model specifically tailored for the sago industry. This model is designed to assess sustainability performance by considering diverse indicators that reflect environmental, economic, and social dimensions of sustainability. The flexibility of the model, according to the authors, allows it to take into account the intricacies and dynamics present in the sago supply chain, which is essential for efficient decision-making and performance enhancement. This model integrates both qualitative and quantitative data, allowing for a comprehensive evaluation of various sustainability indicators pertinent to the sago supply chain. Moreover, the study underscores the necessity of integrating various data collection methods, including observations, interviews, and measurements, to ensure a robust assessment framework. This approach not only enhances the reliability of the data but also allows for a nuanced understanding of the sustainability challenges faced by the sago industry. The findings suggest that the model can effectively identify areas for improvement and facilitate the development of strategies aimed at enhancing sustainability across the supply chain. Furthermore, the integration of fuzzy logic into sustainability assessments allows for the handling of uncertainty and imprecision in data, which is particularly beneficial in the context of agro-industrial supply chains where qualitative factors often play a critical role. This capability is essential for developing a more holistic understanding of sustainability performance, as it enables decision-makers to incorporate subjective judgments alongside objective measurements.” Rewrite the Conclusion section Has been corrected according to the reviewer’s instructions “This work develops a two-stage sustainability evaluation model for the supply chain of the sago agro-industry using the FIS (Fuzzy Inference System) and ANFIS (Adaptive Neuro-Fuzzy Inference System). The proposed sustainability assessment model is reliable and can be utilized based on the results of model verification and validation. The FIS model that has been created is capable of assessing the sustainability performance of the sago agro-industry, both in terms of industrial-scale and small-medium-scale operations, across all aspects. The industrial-scale sago agro-industry's supply chain sustainability performances are scored as follows: 53.17 (almost sustainable) in the environmental dimension, 55.29 (almost sustainable) in the social dimension, and 37.74 (unsustainable) in the economic dimension. Within the small-medium scale, the ratings are 56.61 (almost sustainable), 50 (nearly sustainable), and 24.88 (not sustainable), respectively. The ANFIS concept includes grid partition initiation that integrates supply chain sustainability performance across all aspects. The ANFIS model exhibits negligible training and testing mistakes, indicating its capacity to effectively evaluate supply chain sustainability performance. The validation procedure indicates that the sago agro-industry has a supply chain sustainability performance of 44.25 in the industrial-scale industry and 48.81 in the small-medium scale. This performance categorizes it as being almost sustainable. Important elements that enhance supply chain sustainability performance are also examined in this study. The fair distribution of profits among supply chain participants, institutional support for supply chains, effective waste management infrastructure, and the efficient use of waste through reuse and recycling are all critical elements in improving the sustainability of the supply chain for the sago agro-industry.” Please proof check the whole manuscript Thank you for your feedback. We will double check the entire manuscript to ensure its quality before submission to the journal. Criticism and suggestions from reviewers are very valuable for us to improve the quality of this research. Thank you for your attention. Please match the citation and references Thank you for your feedback. We will revise the article to ensure that the citation and references are properly matched. We appreciate your attention to detail and will strive to improve the quality of the research."
}
]
}
] | 1
|
https://f1000research.com/articles/12-593
|
https://f1000research.com/articles/13-933/v1
|
20 Aug 24
|
{
"type": "Research Article",
"title": "The effect of soaking heat-polymerized acrylic resin denture base in avocado seed extract (Persea americana Mill.) on the inhibition of denture-plaque microorganisms biofilm growth ",
"authors": [
"Thalia Angela",
"Siti Wahyuni",
"Susanna Halim",
"Thalia Angela",
"Susanna Halim"
],
"abstract": "Background Heat polymerized acrylic (HPA) resins are known to have high porosity that contributes to increased surface roughness and microcrack formation in stress areas. This facilitates the attachment and growth of polymicrobial biofilms contributing to increased antimicrobial resistance. Many research had been carried out on avocado seeds, but no research that studies the effect of avocado seeds on denture-plaque microorganism biofilm on HPA resin has been found.\n\nMethods This study used 144 samples (n=144), namely HPA resin discs covered with mono-species and polymicrobial biofilms consisting of Candida albicans, Candida glabrata, Actinomyces odontolyticus, Streptococcus gordonii, and Staphylococcus aureus. The discs were soaked for 8 hours in the 5%, 10%, 15%, 20% avocado seed extract, positive control (alkaline peroxide), and negative control (aquadest). Each disc was shaken with a vortex mixer for 1 minute, and 100 μL was added into 96-well microplates with three times repetition and incubated for 24 hours. The inhibition values were determined from the percentage inhibition value formula which required absorption values from a microplate reader (595 nm).\n\nResults In this research, it was found that the MBIC50 of avocado seed extract against the mono-species of C. albicans (5%), C. glabrata (5%), A. odontolyticus (15%), S. gordonii (15%), S. aureus (10%), while against the biofilm was 20%. There was a significant effect of soaking HPA resin in avocado seed extract of 5%, 10%, 15%, 20% on the inhibition of mono-species and polymicrobial biofilms of denture-plaque microorganisms with a value of p<0.001 (p<0.05).\n\nConclusion The MBIC50 of avocado seed extract in polymicrobial biofilm group was higher than that in the mono-species biofilm groups. Although alkaline peroxide showed higher inhibition value than that of the MBIC50 in polymicrobial biofilm group, 20% avocado seed extract was effective in inhibiting polymicrobial biofilm because it was able to inhibit more than 50% polymicrobial biofilm.",
"keywords": [
"heat polymerized acrylic resin",
"avocado seed extract",
"mono-species biofilm",
"polymicrobial biofilm",
"denture plaque",
"MBIC"
],
"content": "Introduction\n\nThe denture base is a part of the denture which rests on the supporting tissue and serves as a place for the arrangement of tooth elements.1 Denture base materials vary greatly, but the most commonly used and popular material is polymethyl methacrylate acrylic resin (PMMA) with more than 95% of fabricated denture bases are made from acrylic resin.2,3 Acrylic resin itself has various types, one of which is heat polymerized acrylic resin.4 Heat polymerized acrylic (HPA) resin has better strength properties and a higher degree of polymerization, less residual monomer, and more stable color.5,6 However, it still has limitations, some of which have porous properties and high surface roughness which can increase the attachment of fungal and bacterial biofilms.4\n\nColonization in a biofilm requires strong attachment of oral microorganisms by integrating into the salivary pellicle to form plaque on the denture material. Surface roughness and surface free energy are two factors that can promote plaque development.7 Surface roughness of acrylic resin can be reduced by adequate polishing. However, this cannot prevent the build-up of plaque on the denture due to the presence of microporosity in the acrylic resin which cannot be completely avoided.4 This area of porosity becomes an environment which can protect microorganisms in the biofilm.7 In addition, the abiotic surface of the denture causes less exposure of the denture biofilm to the host immune system so that microorganisms can grow without hindrance and have sufficient time to develop into plaque with varying compositions.8\n\nO’Donnell et al. (2015) stated that the composition and diversity of dental plaque was different from denture plaque. Denture plaque in the oral cavity was found to be colonized by Candida spp. against the denture surface which co-aggregated with bacteria in the oral cavity.8 As many as 60% to 100% of denture wearers were found to carry Candida in the oral cavity in higher quantities compared to those who did not wear dentures.8,9 The commonly found Candida species in denture plaque is Candida albicans. Another Candida species that is found in denture plaque and increases with age is Candida glabrata. Together with C. albicans, these two fungal species can form more pathogenic and invasive biofilms and increase the severity of denture stomatitis.8 Several studies have found that denture plaque compared to dental plaque has a higher proportion of obligate anaerobic Actinomyces spp., a low proportion of Gram-negative rods, and the common presence of Staphylococcus aureus a.10 Shi et al. (2016) found that the genus of bacteria which was most commonly found on both surfaces of denture teeth and remaining natural teeth was the genus Actinomyces, followed by Streptococcus, Veillonella, Capnocytophaga, Neisseria, Prevotella, and Corynebacterium.11 Based on the genus mentioned, the bacterial species which will be used in this study were Actinomyces odontolyticus, Staphylococcus aureus, and Streptococcus gordonii.\n\nThe presence of these three bacteria in dentures can increase the virulence of C. albicans thereby increasing damage and invasion of mucosal tissue which increases the risk of denture stomatitis. Morse et al. (2018) found a significant increase in tissue damage from mixed Candida and bacterial biofilms where the composition of the biofilm was broadly the composition of denture plaque.8,12 The difference between biofilms and planktonic bacteria or fungi is that biofilms are a community of microbial cells enveloped in a matrix, while planktonic bacteria or fungi do not have this matrix layer. The presence of matrix can cause failure of treatment with antimicrobial agents, relapse of infection, and increased mortality.13 Penetration of antimicrobial agents can be complicated due to the formation of extracellular polysaccharides (EPS) which reduce the permeability of the biofilm thereby protecting microorganisms in the deepest layers of the biofilm from antimicrobial agents, minor mechanical stress, and host immune response.14,15 To determine the inhibitory effect of an antimicrobial agent on biofilm formation, it can be done using the Minimum Inhibitory Biofilm Concentration (MBIC), which is almost the same as the MIC. The difference between the two is that MBIC is defined as the lowest concentration of an antimicrobial agent at which there is no time-dependent increase in the average number of cells capable of surviving in the biofilm. Meanwhile, MIC is defined as the lowest concentration of an antimicrobial agent against planktonic microorganisms.13\n\nTo prevent the accumulation of denture plaque, adequate and routine denture cleaning needs to be done. Denture cleaning can be done chemically using alkaline peroxide type denture cleaning agent. However, alkaline peroxide was found not to show stable biofilm cleaning efficacy with previous studies showing that alkaline peroxide was not effective in cleaning biofilm and was only effective in cleaning new plaque.16,17 Therefore, it is necessary to develop a denture cleanser product in solution preparation with natural ingredients that have antimicrobial effects which can effectively clean denture plaque. One example of natural ingredient that can be used as an antimicrobial and antibiofilm agent is avocado seeds.\n\nAvocados (Persea americana Mill.) are one of the most popular types of fruit among Indonesian and are widely used as food ingredients (salads, sandwiches, cakes) and drinks (juice, ice cream), cosmetic ingredients, medicines and ornamental plants.18 However, avocado seeds have no practical use and have not been utilized optimally so they tend to be an organic waste.19 Avocado seed can actually be used as an antimicrobial agent because of the higher amounts of phytochemical components contained in avocado seed, namely flavonoids, tannins, saponins, and alkaloids, than in avocado skin and pulp, which are 64% in seed, 23% in skin, and 13% in pulp.20,21 The inhibitory effects of avocado seed extract has been studied. Anggraini et al. (2017) studied the inhibition zone of avocado seed extract at concentrations of 10%, 20%, 40%, 80%, 100% on the growth of C. albicans, and found that the 10% concentration was the most effective concentration in inhibiting C. albicans.22 Another study by Talib et al. (2018) tested the effectiveness of avocado seed extract in inhibiting Streptococcus mutans at concentrations of 2%, 4%, 6%, 8%, 10% and found that the most effective concentration was 10%.23\n\nHowever, most studies using avocado seed extract were carried out on planktonic bacteria or fungi, which is different from denture plaque in the patient’s oral cavity, which is a polymicrobial biofilm that tends to be more resistant to antimicrobial agents. This can be seen in a study by Hamzah et al. (2019) who found an increase in the minimum inhibitory concentration of tannin in polymicrobial biofilms (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) when compared to the concentration in mono-species biofilms. The minimum inhibitory concentration of tannin in mid-phase polymicrobial biofilms (24 hours) is 1%, while the minimum inhibitory concentration of tannins in mono-species biofilms (24 hours) varies widely, namely E. coli (0.125%), S. aureus (0.5%), P. aeruginosa (0.25%), C. albicans (0.5%).24 Hence, this study aimed to determine the effect of avocado seed extract (Persea americana Mill.) with concentrations of 5%, 10%, 15%, 20% on denture-plaque microorganisms, which were Candida albicans, Candida glabrata, Actinomyces odontolyticus, Streptococcus gordonii, and Staphylococcus aureus, in the form of mono-species and polymicrobial biofilms on HPA resin.\n\n\nMethods\n\nAvocados were obtained from Brastagi, Karo Regency, North Sumatra Province, Indonesia. The avocado fruit used in this research has been determined by the Medanense Herbarium Plant Systematics Laboratory (MEDA) at the University of Sumatera Utara with letter number 1835/MEDA/2023.\n\nThis research used in vitro experimental methods with post-test only control group design. The sample used in this research was HPA resin in the shape of a disc with a diameter of 10 mm and a thickness of 2 mm (Figure 1). The number of samples used in this study was determined using Federer formula, hence the number of samples for each group was 4 samples. There were 6 treatment groups in this study which were avocado seed extract groups of 5%, 10%, 15%, 20%, as well as the positive control group (alkaline peroxide) and the negative control group (aquadest). As this research was conducted on mono-species biofilms: Candida albicans, Candida glabrata, Streptococcus gordonii, Actinomyces odontolyticus, Staphylococcus aureus, and on polymicrobial biofilm which is a combination of the five microorganisms, the final total amount sample that would be used in this research was 144 samples (n=144).\n\nA disc-shaped brass metal master models with a diameter of 10 mm and a thickness of 2 mm were made to be used as a research sample mould. The dental cuvette, which had been smeared with Vaseline, was poured with a type II blue dental stone gypsum mixture made with a ratio of 300 g of gypsum: 90 mL of water to fill the bottom cuvette while being shaken with a vibrator so that no bubbles were trapped in the mixture. The master models, which had been smeared with vaseline, were then placed in the dough in a cuvette, avoiding the surface of the master models being flat with the gypsum surface. The gypsum was left to harden for ± 30-45 minutes and then smeared with vaseline. The upper cuvette was attached to the lower cuvette and filled with the same gypsum mixture as described previously. After the plaster had hardened, the cuvette was opened and the master models were taken out to obtain a mould.\n\nThe surface of the mould was smeared thinly with cold mould seal and left for 10 minutes. The HPA resin mixture was prepared with a weight ratio of 2.5:1. When it reached the dough stage, the acrylic resin mixture was put into the mould, then covered with plastic cellophane along with the top cuvette. The cuvette was pressed slowly with a hydraulic press until the pressure reached 1000 psi. Excess dough was cleaned with dental lecron, then the cuvette was closed and pressed again with a pressure of 2200 psi. The cuvette was reopened and cleaned of excess acrylic resin mixture. The cuvette was closed again and locked with the cuvette bolts, then left for 30 minutes. The cuvette was inserted into a water bath filled with aquadest, then the temperature and time were set at 70°C for 90 minutes, then at 100°C for 30 minutes. After 30 minutes, the cuvette was left in the water bath until the water reached room temperature for the cuvette cooling process. The samples were removed from the cuvette, then the sharp parts and plaster residue were trimmed with a fraser bur and sand paper.\n\nAvocado seeds were extracted using a maceration technique. The avocado seeds would be cut into slices which would be dried in a drying cabinet at a temperature of ±40°C for about 24 hours, then coarsely grounded and blended until they became a fine powder. The avocado seed powder was put into a vessel and poured with 70% ethanol solvent with a ratio of 1:10 (10 g: 100 mL), then stirred until evenly mixed and left for 1×24 hours protected from light while stirring periodically every 6 hours so that the solution was evenly mixed. The solution was filtered until macerate I was obtained and the remaining filtered dregs were subjected to a second maceration process. The results of macerate I and II would be mixed and transferred into a closed vessel, then left in a cool place protected from light for 2×24 hours. The extract was concentrated using a rotary evaporator at a temperature of ±50°C to evaporate the solvent until a thick extract was obtained. The thick extract was then made into a concentration of 5%, 10%, 15%, 20%.\n\nThe thick extract of avocado seeds was sent to the Pharmaceutical Biology Laboratory, University of Sumatera Utara, Medan for phytochemical examination and quantitative testing of phytochemical compounds.\n\nThe microorganisms used in this study were cultured and maintained under the following conditions. Candida albicans ATCC® 24433TM and Candida glabrata ATCC® 90030TM were each cultured on Sabouraud Dextrose Agar (SDA) with yeast nitrogen base supplemented with 100 mmol L−1 glucose and cultured at 37°C under aerobic conditions for 24 hours. Actinomyces odontolyticus ATCC® 10558TM was cultured on fastidious anaerobe agar with 5% (v/v) defibrinated bovine blood at 37°C under anaerobic conditions for 24 hours. Streptococcus gordonii ATCC® 10558TM was cultured on blood agar with 5% (v/v) defibrinated bovine blood at 37°C under aerobic conditions for 24 hours. Staphylococcus aureus ATCC® 25923TM was cultured on blood agar with 5% (v/v) defibrinated bovine blood and incubated at 37°C under aerobic conditions for 24 hours.\n\nSterile HPA resin discs were preconditioned for 24 hours by immersion in artificial saliva. The density of the microorganism cultures must be adjusted using a densitometer following the 0.5 McFarland standard, namely 1.5 × 108 CFU/mL for bacterial suspensions (A. odontolyticus, S. gordonii, S. aureus) and 1.0 McFarland standard, namely 3.0 × 108 CFU/mL for fungal suspensions (C. albicans and C. glabrata). The preconditioned discs were then placed aseptically into 24-microplates, and 100 μL of standardized microorganisms were added to each surface of the disc. Biofilm preparations carried out were mono-species biofilms for each microorganism studied (C. albicans, C. glabrata, A. odontolyticus, S. gordonii, S. aureus) and polymicrobial biofilms which were a combination of the five microorganisms studied. Sterile Dulbecco’s Modified Eagle Medium (DMEM) (supplemented with 50 mmol L-1 L-glutamine per liter) was added to a final volume of 2 mL in each plate. Culture media discs in 24-wells microplates were shaken on an orbital shaker for 30 minutes to homogenize the media and culture solutions, then incubated at 37°C for 24 hours.\n\nHPA resin discs which had been grown by mono-species and polymicrobial biofilms would be treated with immersion in avocado seed extract of 5%, 10%, 15%, 20%, as well as positive control (alkaline peroxide) and negative control (aquadest) for 8 hours at room temperature. The discs were then cleaned with distilled water, then put into a test tube together with 5 mL of Mueller Hinton broth and each shaken with a vortex mixer for 1 minute. A total of 100 μL of test solution was taken from the dilution and added into 96-wells microplates with a repetition of three times. Microplates were incubated at 37°C for 24 hours. After incubation, the microplates were cleaned with distilled water and patted vigorously on a lab mat to remove as much distilled water as possible. As much as 125 μL of 1% crystal violet solution was added to each microplate to colour the formed biofilm and left for 15 minutes. The crystal violet solution was discarded, then cleaned with distilled water and patted hard on a lab mat. The stained biofilm plates were allowed to dry until the remaining water in the microplates evaporated, then 150 μL of 95% ethanol was added to each plate and left for 10 minutes. The absorption value (OD) reading was carried out with a microplate reader at a wavelength of 595 nm and the results were calculated using the percentage inhibition value formula of which Control OD was defined as negative control absorption value and Sample OD was defined as test sample absorption value.24\n\nThe treated sample which had an inhibition value of at least 50% of biofilm formation could be considered as the Minimum Biofilm Inhibitory Concentration (MBIC50).24\n\nUnivariate analysis was carried out to determine the average (mean) and standard deviation of the inhibition values for immersion of heat polymerized acrylic resin discs in each group. The conversion of absorption value to inhibition value in percentage is counted using the percentage inhibition value formula that had been coded in Excel 2021 software. The normality test was carried out using the Shapiro-Wilk test (p>0.05) and the homogeneity test was carried out using the Levene test (p>0.05). Data analysis was carried out using one-way ANOVA, which could be accompanied by Welch ANOVA on non-homogeneous data, to determine the effect of treatment in each group. Data were analyzed with IBS SPSS Statistics (RRID: SCR_016479) v.22.0 software and presented in tabulation and graphic form as mean and standard deviation. Significant differences were defined at p<0.05.\n\nThe SEM procedure was carried out at the USU Integrated Research Laboratory, Medan. HPA resin disc samples that had been preconditioned with artificial saliva were then grown with polymicrobial biofilm according to the previous biofilm formation procedure and given a soaking treatment in avocado seed extract. HPA resin disc samples that had biofilm grown on were cleaned with distilled water three times and fixed with 2.5% (w/v) glutaraldehyde in cacodylate buffer for about 6 hours. The wet sample was then coated with a thin layer of gold to make the sample conductive. Sample reading using SEM was carried out with a voltage of 5 kV.\n\nThe denture base subjects’ research was approved on 27th February 2024 and performed according to the ethical standards by the Health Research Ethics Committee of the University of Sumatera Utara, Indonesia as stated in letter number 166/KEPK/USU/2024.\n\n\nResults\n\nIn this study, there were 6 treatment groups consisting of samples of HPA resin discs soaked in avocado seed extract 5%, 10%, 15%, 20%, as well as a positive control (alkaline peroxide) and a negative control (aquadest). The HPA resin disc samples were grown with mono-species biofilms of C. albicans, C. glabrata, A. odontolyticus, S. gordonii, S. aureus and polymicrobial biofilms so that the number of samples in this study was 144 samples (n=144).\n\nThe following are the results of avocado identification by the Medanense Herbarium, University of Sumatera Utara.\n\nKingdom: Plantae\n\nDivision: Spermatophyta\n\nClass: Dicotyledoneae\n\nOrder: Laurales\n\nFamily: Lauraceae\n\nGenus: Persea\n\nSpecies: Persea americana Mill.\n\nLocal Name: Avocado Seed\n\nThe phytochemical test on the ethanol extract of avocado seeds was done using specific reagents to determine the presence of secondary metabolite compounds which were alkaloids, flavonoids, glycosides, saponin, tannin, triterpenoids/steroids (Table 1). The test showed positive results of all the tested secondary metabolite compounds and none negative results.\n\nThe secondary metabolite compounds existing in the avocado seed ethanol extract could be further assessed by doing a quantitative analysis to determine the amount of the secondary metabolites in the sample extract which were flavonoids, phenol, saponin, and alkaloids (Table 2). The analysis showed a total amount of phenol (66,8157 mgGAE/g extract), total amount of flavonoids (4,0888 mgQE/g extract), total percentage of saponin (1,59%), and total percentage of alkaloids (1,22%).\n\nEach sample in each group was repeated three times to obtain three absorption values (OD) which then using univariate analysis, the mean and standard deviation were obtained. The obtained absorption value was calculated using the percentage inhibition value formula with an inhibition value of 50% as a parameter for determining MBIC50 (Figure 2). Based on calculations, MBIC50 of avocado seed extract in mono-species C. albicans biofilm was 5% avocado seed extract. MBIC50 avocado seed extract in mono-species C. glabrata biofilm was 5% avocado seed extract. MBIC50 avocado seed extract in mono-species A. odontolyticus biofilm was 15% avocado seed extract. MBIC50 avocado seed extract in mono-species S. gordonii biofilm was 15% avocado seed extract. MBIC50 avocado seed extract in mono-species S. aureus biofilms was 10% avocado seed extract.\n\nThe sample was tested for normality and a value of p>0.05 was obtained, hence the data were normally distributed. Then, a homogeneity test was carried out by which the mono-species C. albicans biofilm sample obtained a value of p<0.001 (p<0.05), the mono-species A. odontolyticus biofilm sample obtained a value of p=0.002 (p<0.05), and the mono-species S. gordonii biofilm sample obtained a value of p≤0.001 (p<0.05) so the data were not homogeneous, while the mono-species C. glabrata biofilm sample obtained a value of p=0.054 (p>0.05) and the mono-species S. aureus biofilm sample obtained a value of p=0.116 (p>0.05) so the data were homogeneous. Data which was normally distributed and homogeneous was tested using one-way ANOVA and data which was normally distributed but not homogeneous was analysed using Welch ANOVA. This study found that mono-species biofilm samples of C. albicans, C. glabrata, A. odontolyticus, S. gordonii, S. aureus obtained a value of p≤0.001 (p<0.05) which indicated a significant effect of 5%, 10%, 15%, 20% avocado seed extract in inhibiting mono-species biofilms of C. albicans, C. glabrata, A. odontolyticus, S. gordonii, S. aureus (Table 3).\n\n* Significant, absorption values are in mean and standard deviation.\n\nIn this study, three absorption values (OD) of polymicrobial biofilm samples were obtained from which the mean and standard deviation were obtained using univariate analysis. Using the percentage inhibition value formula, the inhibition values were obtained for each group of avocado seed extract of 5%, 10%, 15%, 20%, and the positive control (alkaline peroxide) where the 50% inhibition value was set as a parameter for determining MBIC50 (Figure 3). Hence, the MBIC50 avocado seed extract in polymicrobial biofilm was 20% avocado seed extract.\n\nThe sample was tested for normality and a value of p >0.05 was obtained, hence the data was normally distributed. Then, a homogeneity test was carried out by which the polymicrobial biofilm samples obtained a value of p=0.006 (p<0.05) so that the data was not homogeneous. Data that were normally distributed but not homogeneous were analysed using the Welch ANOVA. This study found that the polymicrobial samples obtained a value of p≤0.001 (p<0.05) which indicated a significant effect of soaking in 5%, 10%, 15%, 20% avocado seed extract in inhibiting polymicrobial biofilm (Table 4).\n\n* Significant, absorption values are in mean and standard deviation.\n\nBased on the Integrated Laboratory Test Results Report of the University of Sumatera Utara with the number 113/UN5.4.6.K/KPM/2024, the results of SEM tests carried out on HPA resin discs with polymicrobial biofilm which had been soaked with avocado seed extract could be detected and clearly seen in Figure 4 below. SEM results showed that there were microorganisms growing on the HPA resin disc. The soaking in 5% avocado seed extract showed a denser formation of biofilm compared to soaking in 15% avocado seed extract.\n\n\nDiscussion\n\nDenture plaque is not the same as dental plaque, although the microbial composition of denture plaque is influenced to a certain extent by dental plaque because the microbiota on the denture surface and the tooth surface originates from the same oral cavity. However, Fujinami et al. (2021) and O’Donnell et al. (2015) found lower diversity in denture plaque compared to dental plaque which may be caused by differences in the surface on which it grows.8,25 Low diversity in denture plaque, and the denture environment in the underlying tissue which is low in oxygen levels and saliva flow, as well as denture surface characteristics in the form of porosity and non-specific factors such as hydrophobicity, van der Waals forces, Brownian motion forces, and electrostatic interactions support the adhesion and growth of Candida spp. to colonize denture surfaces and form co-aggregates with bacteria to form complex microbial communities.8,26,27\n\nCandida albicans has the pathogenic ability in the form of morphogenesis, which is the ability to transition C. albicans from a unicellular yeast form to a pathogenic filament form (pseudohyphae or hyphae) reversibly.28,29 C. albicans yeast cells will adhere to the denture surface via A1s1-8p adhesin, then proliferate to form microcolonies which become the basal layer of the biofilm and produce extracellular matrix (ECM). As the biofilm matures, there is an increase in biomass with the presence of yeast cells, hyphae and pseudohyphae encapsulated in the extracellular matrix. These hyphae are fundamental and important components in supporting the structural integrity of the biofilm and provide a means of attachment for additional yeast cells, pseudohyphae, other hyphae, and bacteria due to their ability to express specific adhesins such as Hwp1p and Hyr1p.15 These hyphae are also capable of damaging epithelial cells and destabilizing membranes through induced calcium ion influx and release of lactate dehydrogenase.9 In this study, the MBIC50 of avocado seed extract in mono-species C. albicans biofilm was 5% avocado seed extract with an inhibition value of 76.09 ± 3.21%. This is in accordance with previous research by Wulandari et al. (2023) who tested the effect of avocado seed extract on C. albicans biofilms. Using the inhibition percentage formula, the lowest concentration of avocado seed extract tested, which is a concentration of 3.13%, was able to inhibit C. albicans biofilms incubated for 24 hours by 75.37%.30\n\nCandida glabrata is the second most frequently isolated cause of candidiasis and is often found together with C. albicans in the form of co-isolation in which C. glabrata budding yeast is found attached to C. albicans hyphae.31 There was still little to none research done on the effect of avocado seed extract on C. glabrata. This study found that the MBIC50 of avocado seed extract in mono-species C. glabrata biofilm was 5% avocado seed extract with an inhibition value of 52.41 ± 9.64%. When compared with the C. albicans inhibition value, there was a decrease in the biofilm inhibition activity of avocado seed extract against C. glabrata. This is due to the higher antifungal resistance in C. glabrata than in C. albicans, and the rapid ability of C. glabrata to develop resistance to currently used antifungal agents.32 Farahyar et al. (2016) found that C. glabrata had Candida drug-resistant (CgCDR) genes CgCDR1 and CgCDR2, and Fatty Acid Activator 1 (FAA1) which was positively regulated twice as much in resistant strains.33 Yu et al. (2018) found that another factor that played an important role in the antifungal tolerance and cell wall integrity of C. glabrata is ADA2 which was mediated by the ERG6 gene.34\n\nBacteria are thought to play an important role in the formation of denture plaque considering that denture plaque can contain 1011 microbes per milligram.8 Actinomyces is a genus commonly found in denture plaque with a large proportion which can be caused by the ability of C. albicans biofilms to provide a positive anaerobic environment to some anaerobic bacteria so that Actinomyces which is an anaerobic bacteria can easily grow in oxygen-rich areas.10,29 However, the clinical significance of Actinomyces spp. still needs to be proven and the available data regarding the antimicrobial susceptibility of Actinomyces is still limited with the susceptibility method which has not been standardized. In this study, the MBIC50 of avocado seed extract against the mono-species Actinomyces odontolyticus biofilm was high, namely 15% avocado seed extract with an inhibition value of 50.88 ± 7.31%. This can be explained by several studies which had found the existence of antimicrobial agent resistance or antibiotic resistance in A. odontolyticus. Wolff et al. (2022) found an A. odontolyticus isolate that showed multi-drug resistance (MDR) to benzylpenicillin, meropenem, moxifloxacin, and daptomycin.35 Steininger et al. (2016) tested the susceptibility of Actinomyces spp. taken from 387 patients over a 7-year period and found that Actinomyces spp. was susceptible to β-lactam antimicrobial agents with and without β-lactamase inhibitors and there was an A. odontolyticus isolate that was resistant to tetracycline.36\n\nShi et al. (2016) found that S. gordonii colonized denture teeth in healthy denture users at a significantly higher rate.11 In this study, the MBIC50 of avocado seed extract in mono-species S. gordonii biofilm was 15% avocado seed extract with an inhibition value of 51.16 ± 4.74%. There was still no research done on the effect of avocado seed extract on S. gordonii, but most researches on S. mutans had been carried out, where these researches focused on treating caries and dental plaque rather than denture plaque. Calosa et al. (2023) found that the minimum inhibitory level of avocado seed extract against S. mutans as seen from the sample absorbance was 12.5%.37 S. gordonii usually competes with S. mutans where S. gordonii metabolically produces hydrogen peroxide which is able to inhibit the growth of S. mutans, and produces alkaline ammonia which is able to mitigate acidity on the tooth surface. The presence of S. mutans in plaque is strongly and positively associated with caries while S. gordonii is negatively associated with caries.38 Considering the antagonistic relationship between S. mutans and S. gordonii, the presence of S. gordonii in denture plaque minimizes the presence of S. mutans.37 Further research into the effects of avocado seeds on S. gordonii needs to be carried out.\n\nS. aureus is often associated with higher amount in the elderly, seriously ill patients, individuals with low salivary secretion, and denture wearers.39 S. aureus is also commonly found in patients with oral infections associated with Candida albicans, such as denture stomatitis and angular cheilitis, due to the nature of S. aureus which tends to attach more easily to the hyphal phase of C albicans compared to abiotic surfaces.40 In this study, the MBIC50 of avocado seed extract in mono-species S. aureus biofilm was 10% avocado seed extract with a value of inhibition was 51.63 ± 5.05%. Research on the effect of avocado seed extract on S. aureus that has been carried out has found the Minimum Inhibitory Concentration (MIC) of avocado seed extract, but not the MBIC. Santosa et al. (2019) using the zone of inhibition test concluded that avocado seed extract was effective in inhibiting multi-resistant S. aureus at a concentration of 6.25%.41\n\nThis study found a significant effect of soaking in avocado seed extract (Persea americana Mill.) concentrations of 5%, 10%, 15%, 20%, as well as the positive control of alkaline peroxide in inhibiting the growth of denture plaque microorganisms on HPA resin discs in the form of C. albicans, C. glabrata, A. odontolyticus, S. gordonii, and S. aureus mono-species biofilms, each with a value of p≤0.001 (p<0.05). If the inhibition value of avocado seed extract was compared with the inhibition value of the positive control alkaline peroxide, only the MBIC50 inhibition value of avocado seed extract on mono-species C. albicans biofilm (76.09 ± 3.21%) was found to be higher than the inhibition value of the positive control (66, 43 ± 28.29%). In other mono-species biofilms, such as C. glabrata, A. odontolyticus, S. gordonii, S. aureus, the inhibition value of avocado seed extract was lower than the inhibition value of the positive control. Morelli et al. (2023) stated that effervescent tablets showed good antimicrobial activity against C. glabrata, S. mutans, and S. aureus on a cobalt-chromium surface. However, none of these peroxide-based solutions showed a reduction in C. albicans biofilms or substantially eliminated aggregated biofilms.42\n\nFrom the research results, the MBIC50 of avocado seed extract against polymicrobial biofilm in this study was 20% avocado seed extract with an inhibition value of 50.81 ± 8.32%. When compared with MBIC50 in mono-species biofilms, it was found that polymicrobial biofilm required a higher concentration of avocado seed extract. This is in accordance with research results which state that polymicrobial biofilms have higher resistance to antimicrobial agents compared to mono-species biofilms. O’Brien et al. (2022) who tested three clinically relevant antimicrobial agents namely colistin, fusidic acid, and fluconazole against polymicrobial populations containing P. aeruginosa, S. aureus, and C. albicans found a higher antimicrobial agent resistance in polymicrobial biofilm compared to mono-species biofilms. These researchers found that there was a decrease in antimicrobial activity against target microorganisms in polymicrobial cultures compared to mono-species cultures.43 However, Kart et al. (2014) stated that polymicrobial biofilms did not always have higher resistance compared to mono-species biofilms as its susceptibility to antimicrobial agents depends on the nature of the microbial species present and the disinfectant used.44\n\nIn polymicrobial biofilms, the interactions between microbes are very complex, some of which include cooperative and antagonistic interactions. Synergism between species in polymicrobial biofilms can produce effects on growth enhancement, antimicrobial resistance, virulence, and greater exopolysaccharide production compared to individual species alone.45 C. albicans and C. glabrata are often found together in the form of co-isolates that cause increased pathogenicity of both species.46 This is due to the ability of C. albicans to damage host tissue which can be exploited by C. glabrata to reach deeper tissues. C. glabrata itself has very high antifungal resistance capabilities, and is able to modify the maturation of macrophage phagosomes so that they can hide inside macrophages from the host immune system so C. glabrata can produce infections that are much more severe and require quite complicated treatment.47 Other microorganisms that were found to have a very synergistic interaction were S. gordonii and C. albicans. S. gordonii was found to be capable of promoting filamentation and increasing fungal biofilm formation. Higher biomass was also found in polymicrobial biofilms formed by C. albicans and S. gordonii.48 Diaz et al. (2014) showed an increase in the ability of oral streptococci to form biofilms on abiotic surfaces in the presence of C. albicans.49 This is caused by C. albicans adhesins which facilitate the interaction of bacterial species, such as Als1p, Als2p, Als3p, Hwp1p.28 On the other hand, these bacteria is able to influence the local environment of C. albicans by altering nutrient supply and carbon dioxide levels thereby favouring C. albicans’ hyphal transition and virulence.49 The interaction of the two species causes increased resistance to antimicrobial agents.48 The relationship between S. aureus and C. albicans has also been studied extensively where C. albicans can increase S. aureus resistance to vancomycin by 100-fold due to the production of the cell wall component β-1,3-glucan. These compounds were identified as matrix constituents that provide bacteria with increased drug tolerance. In addition, the production of farnesol and prostaglandin E2 by C. albicans can increase S. aureus biofilm formation.50\n\nAntagonistic interactions are a type of competitive interaction where one species will inhibit the growth of another species by producing a variety of secondary metabolites that can inhibit or kill competing species so that the biofilm architecture can be disrupted.45 Guo et al. (2015) found an inhibitory effect of A. odontolyticus on proliferation, adhesion, metabolic enzyme activity, hypha formation, and biofilm development of C. albicans. Actinomyces was found to produce many metabolites with antifungal activity, including lincomycin and geldanamycin.51 However, another study by Morse et al. (2019) showed opposite results and found that polymicrobial biofilms of S. sanguinis, S. gordonii, A. odontolyticus, and A. viscosus were able to increase the number of C. albicans hyphae.52\n\nIn this study, there was a significant effect of soaking in avocado seed extract (Persea americana Mill.) concentrations of 5%, 10%, 15%, 20%, as well as the positive control of alkaline peroxide in inhibiting the growth of polymicrobial biofilm on HPA resin discs with a value of p≤0.001 (p<0.05). The results of this analysis were also supported by SEM results which showed a much sparse biofilm on HPA resin discs soaked in 15% avocado seed compared to those soaked in 5% avocado seed extract. This showed that avocado seed extract had the ability to damage the mucus layer of polymicrobial biofilms. Polymicrobial biofilms are highly structured associations of microorganisms encased in an extracellular matrix (ECM) which attached to biotic or abiotic surfaces. One of the advantages of biofilms to the microorganisms within them is the presence of collective recalcitrant which is defined as the ability of pathogenic biofilms to survive in the presence of high concentrations of antibiotics. Cells in biofilms were found to be 10-1000 times more resistant to various antimicrobial agents than their planktonic forms.53 Polymicrobial biofilms were found to have tolerance to antimicrobial agents and increased virulence due to an extracellular matrix (ECM) containing abundant extracellular polymeric substances (EPS) to protect all microbial cells from various dangers.54 The presence of extracellular matrix (ECM) can influence pH, oxygen concentration, and nutrient availability in the deepest layers of the biofilm. In addition, ECM can limit the penetration of antimicrobial agents and cause the accumulation of antibiotic-degrading enzymes.44 Therefore, increasing the permeability of polymicrobial biofilms is one of the targets of antimicrobial agents to inhibit the microorganisms within them.\n\nIn the phytochemical tests that have been carried out, flavonoid, tannin, alkaloid, saponin, triterpenoid and polyphenol class compounds were found present in avocado seed extract. Followed by quantitative tests of phytochemical compounds, it was found that the total flavonoid content in avocado seed extract was 4.0888 mgQE/g, the total phenol content was 66.8157 mgGAE/g, the total alkaloid content was 1.22%, and the total saponin content was 1. 59%. Vinha et al. (2013) found higher levels of flavonoids and total phenolics in avocado seeds compared to avocado flesh and skin.55 The extraction technique used in the research was the maceration technique, which is a method that is very suitable for secondary metabolite compounds that are sensitive to heat, such as polyphenolic compounds, especially flavonoids, causing the discovery of high levels of flavonoids and polyphenols.26 Flavonoids and tannins are a family of polyphenolic components that are widely distributed in Kingdom Plantae.56 Flavonoids were found to have an antibiofilm effect by penetrating the biofilm layer and inhibiting bacterial growth and attachment. surface. The presence of hydrophilic parts of the chemical structure of flavonoids, including glycoside and hydroxy groups, could increase penetration of the biofilm structure and increase antibiofilm activity.27 Matilla-Cuenca et al. (2020) found that the antibiofilm activity of flavonoids which could inhibit S. aureus biofilm formation was specifically mediated by Bap.57 Tannins were also found to influence the gene expression of virulent factors such as biofilm, enzymes, adhesins, motility and toxins, and act as quorum sensing inhibitors.58 Villanueva et al. (2023) found that all unmodified natural tannins had broad spectrum activity due to their ability to exhibit very significant anti-biofilm activity against Gram-positive and Gram-negative bacteria at least at a concentration of 150 mg/L.59\n\nAlkaloids have been found to damage bacterial cell membranes, inhibit efflux pumps, inhibit ATP synthesis which affects the metabolic processes of microorganisms, damage DNA/RNA molecules or inhibit DNA thereby preventing the expression of virulent genes, and inhibit FtsZ protein synthesis by participating in the diaphragm formation and forming a ring structure in division sites to control the division process and growth of bacterial cells.60 Saponin can reduce the surface tension of bacterial cell walls and damage cell permeability so that saponin can diffuse into the cell and bind to the cytoplasmic membrane which can lead to cell lysis.58 This activity can facilitate the influx of antimicrobial agents to the deeper layers of the polymicrobial biofilm. Brahim et al. (2015) found that the combination of saponin extract with fluconazole showed good synergism against C. albicans, C. parapsolosis, C. krusei, and C. glabrata.61 Monte et al. (2014) showed the potential of saponins in controlling the shape of plankton and biofilms of E. coli and S. aureus.62 Triterpenoids with more polar groups such as hydroxyl, carboxyl and carbonyl have anti-biofilm activity due to their hydrophilic nature so they are able to penetrate the exopolysaccharide polymeric matrix in bacterial biofilms and has an effect on bacterial cells in the biofilm, and shows anti-quorum sensing activity.63\n\nThe inhibition value of the positive control alkaline peroxide against polymicrobial biofilm was found to be higher (63.10 ± 28.26%) than the MBIC50 inhibition value of 20% avocado seed extract (50.81 ± 8.32%). This shows that alkaline peroxide has a good anti-biofilm effect. Kaypetch et al. (2023) found that acrylic resin soaked in alkaline peroxide for more than 3 hours could efficiently penetrate and inhibit multispecies denture biofilm with an effect comparable to immersion in 0.5% NaClO for 10 minutes.64 Research by Lucena-Ferreira et al. (2013) found that daily use of alkaline peroxide could improve denture cleanliness by reducing total microorganisms and total Streptococcus, but had no effect on the Candida spp. population.65 This is contrary to research by Li et al. (2010) who examined the effect of alkaline peroxide on C. albicans biofilms mixed with microorganisms taken from human saliva samples that were conditioned in cases of denture stomatitis and found that alkaline peroxide was able to reduce the viability of Candida growing on the surface of acrylic resin by 3-4 times.66 However, MBIC50 avocado seed extract has been declared effective in inhibiting polymicrobial biofilm with an inhibition value exceeding 50% so that 20% avocado seed extract has the potential to be applied clinically as a natural denture cleanser.\n\nSeveral limitations have been found in this study. First, the diversity and composition of microorganisms in the polymicrobial biofilm in this study is a broad generalization of the diversity and composition of denture plaque in denture wearers. Second, the research was carried out in vitro, which means that all research variables were under the control of the researcher, which cannot be used to represent the condition of the oral cavity in patients using dentures that can be influenced by factors such as age, gender, habits, and so on. Third, this research can only tell how much of the biofilm biomass that can be inhibited with avocado seed extract, but cannot know what microorganisms are inhibited in the polymicrobial biofilm.\n\nThis study did not include any human participants or animal. The denture base subjects’ research was approved on 27th February 2024 and performed according to the ethical standards by the Health Research Ethics Committee of the University of Sumatera Utara, Indonesia as stated in letter number 166/KEPK/USU/2024.",
"appendix": "Data availability\n\nFigshare: Avocado Seed Extract on Inhibiting Mono-species and Polymicrobial Biofilm. https://doi.org/10.6084/m9.figshare.25996006. 67\n\nThis project contains the following underlying data:\n\n• Ethical Clearance No. 166KEPKUSU2024. pdf\n\n• Determination of Avocado Fruit Plants. pdf\n\n• Phytochemical Test Results of Avocado Seed Ethanol Extract. pdf\n\n• Quantitative Analysis for Phytochemical Compounds. pdf\n\n• Research Data of Mono-species C. albicans Biofilm. docx\n\n• Research Data of Mono-species C. glabrata Biofilm. docx\n\n• Research Data of Mono-species A. odontolyticus Biofilm. docx\n\n• Research Data of Mono-species S. gordonii Biofilm. docx\n\n• Research Data of Mono-species S.aureus Biofilm. docx\n\n• Research Data of Polymcrobial Biofilm. docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nFerro KJ: The glossary of prosthodontic terms (GPT-9). J. Prosthet. Dent. 2017; 117(5S): C1–e105. Publisher Full Text\n\nKangsudarmanto Y, Rachmadi P, Arya WI: Perbandingan perubahan warna heat cured acrylic basis gigi tiruan yang direndam dalam klorhesidin dan effervescent (alkaline peroxide). DENTINO. 2014; 2(2): 205–9. 2337-5310.\n\nFadriyanti O, Alamsyah Y, Rabianti D: Evaluasi pemakaian denture adhesive pada gigi tiruan lengkap resin akrilik: Scoping review. Menara Ilmu. 2022; 16(2): 55–62. Publisher Full Text\n\nZarb G, Hobkirk JA, Eckert SE, et al.: Prosthodontic treatment for edentulous patients. 13th ed.St. Louis: Elsevier Mosby; 2013; 133–134.\n\nBohra PK, Ganesh PR, Reddy MM, et al.: Colour stability of heat and cold cure acrylic resins. J. Clin. Diagn. Res. 2015; 9(1): ZC12–ZC15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRashid AA: Temperature effect on the hardness of different types of resin denture base materials. MDJ. 2013; 10(1): 69–76. Publisher Full Text\n\nJain V, Babu J, Ahuja S, et al.: Comparison of fungal biofilm formation on three contemporary denture base materials. Int. J. Exp. Dent. 2015; 4(2): 104–108. Publisher Full Text\n\nO’Donnell LE, Robertson D, Nile CJ, et al.: The oral microbiome of denture wearers is influenced by levels of natural dentition. PLoS One. 2015; 10(9): e0137717. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPatel M: Oral cavity and Candida albicans: Colonisation to the development of infection. Pathogens. 2022; 11(335): 6–8. Publisher Full Text\n\nCoulthwaite L, Verran J: Potential pathogenic aspects of denture plaque. Br. J. Biomed. Sci. 2007; 64(4): 180–189. PubMed Abstract | Publisher Full Text\n\nShi B, Wu T, McLean J, et al.: The denture-associated oral microbiome in health and stomatitis. mSphere. 2016; 1(6): e00215–e00216. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMorse DJ, Wilson MJ, Wei X, et al.: Denture-associated biofilm infection in three-dimensional oral mucosal tissue models. J. Med. Microbiol. 2018; 67: 364–375. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThieme L, Hartung A, Tramm K, et al.: MBEC versus MBIC: The lack of differentiation between biofilm reducing and inhibitory effects as a current problem in biofilm methodology. Biol. Proced. Online. 2019; 21(18): 15–18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKumari KS, Dash P, Subudhi E, et al.: Antimicrobial resistance: A dentists’ prospective. Indian J. Med. Forensic Med. Toxicol. 2020; 14(4): 8456–8460. Publisher Full Text\n\nPonde NO, Lortal L, Ramage G, et al.: Candida albicans biofilms and polymicrobial interactions. Crit. Rev. Microbiol. 2021; 47(1): 91–111. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPeracini A, Regis RR, Souza RF, et al.: Alkaline peroxides versus sodium hypochlorite for removing denture biofilm: A crossover randomized trial. Braz. Dent. J. 2016; 27(6): 700–704. PubMed Abstract | Publisher Full Text\n\nOussama M, Ahmad H: Materials and methods for cleaning dentures- A review. Int. J. Dent. Clin. 2014; 6(2): 19–20. Reference Source\n\nLestari R, Sukamto LA, Aprilianti P, et al.: Selection of avocado plants based on fruit characters, fat content, and continual harvest along the year in west java-indonesia. Int. J. Adv. Sci. Eng. Inf. Technol. 2016; 6(1): 77–83. Publisher Full Text\n\nDomínguez MP, Araus K, Bonert P, et al.: The avocado and its waste: An approach of fuel potential application.Lefebvre G, Jiménez E, Cabañas B, editors. Environment, energy and climate change II: Energies from new resources and the climate change. Switzerland: Springer Cham; 2016; 199–223. Publisher Full Text\n\nSetyawan HY, Sukardi S, Puriwangi CA: Phytochemicals properties of avocado seeds: A review. IOP Conf. Ser.: Earth Environ. Sci. 2021; 733(1): 012090–012097. Publisher Full Text\n\nBahru TB, Tadele ZH, Ajebe EG: A review on avocado seed: Functionality, composition, antioxidant and antimicrobial properties. Chem. Sci. Int. J. 2019; 27(2): 1–10. Publisher Full Text\n\nAnggraini V, Masfufatun M: Efektivitas kombinasi ekstrak daun sirih merah (Piper crocatum) dan ekstrak biji alpukat (Persea americana) dalam menghambat pertumbuhan Candida albicans. Jurnal Kimia Riset. 2017; 2(2): 86–92. Publisher Full Text\n\nThalib B, Nahar CL: Efektivitas antibakteri ekstrak biji alpukat (Persea americana Mill.) terhadap Streptococcus mutans. Makassar Dent. J. 2018; 7(1): 26–29. Publisher Full Text\n\nHamzah H, Hertiani T, Pratiwi SUT, et al.: The inhibition activity of tannin on the formation of mono-spesies and polymicrobial biofilm Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Trad. Med. J. 2019; 24(2): 110–118. Publisher Full Text\n\nFujinami W, Nishikawa K, Ozawa S, et al.: Correlation between the relative abundance of oral bacteria and Candida albicans in denture and dental plaques. J. Oral Biosci. 2021; 63: 175–183. PubMed Abstract | Publisher Full Text\n\nAbubakar AR, Haque M: Preparation of medicinal plants: Basic extraction and fractionation procedures for experimental purposes. J. Pharm. Bioallied Sci. 2020; 12(1): 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMajnooni MB, Ghanadian SM, Mojarrab M, et al.: Antibacterial, antibiofilm, antiswarming, and antioxidant activities of flavonoids isolated from Allium colchicifolium leaves. J. Food Biochem. 2023; 2023: 1–14. Publisher Full Text\n\nNadeem SG, Shafiq A, Hakim ST, et al.: Effect of growth media, pH, and temperature on yeast to hyphal transition in Candida albicans. Open J. Med. Microbiol. 2013; 03: 185–192. Publisher Full Text\n\nAtriwali T, Azeem K, Husain MF, et al.: Mechanistic understanding of Candida albicans biofilm formation and approaches for its inhibition. Front. Microbiol. 2021; 12: 638609. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWulansari S, Mintarjo DF: Efek ekstrak etanol biji alpukat (Persea americana) terhadap biofilm Candida albicans. JKGT. 2023; 5(1): 239–243. Publisher Full Text\n\nHassan Y, Chew SY, Than LTL: Candida glabrata: Pathogenicity and resistance mechanisms for adaptation and survival. J. Fungi. 2021; 7(667): 1–18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVale-Silva L, Sanglard D: Tipping the balance both ways: Drug resistance and virulence in Candida glabrata. FEMS Yeast Res. 2015; 15(fov025): 1–8. PubMed Abstract | Publisher Full Text\n\nFarahyar S, Zaini F, Kordbacheh P, et al.: Expression of efflux pumps and fatty acid activator one genes in azole resistant Candida glabrata isolated from immunoccompromised patients. Acta Med. Iran. 2016; 54(7): 459–464. PubMed Abstract\n\nYu S, Chang Y, Chen Y: Deletion of ADA2 increases antifungal drug susceptibility and virulence in Candida glabrata. Antimicrob. Agents Chemother. 2018; 62(3): e01924–e01917. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWolff A, Rodloff AC, Vielkind P, et al.: Antimicrobial susceptibility of clinical oral isolates of Actinomyces spp. Microorganisms. 2022; 10(125): 1–11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSteininger C, Willinger B: Resistance patterns in clinical isolates of pathogenic Actinomyces species. J. Antimicrob. Chemother. 2016; 71: 422–427. Publisher Full Text\n\nCalosa BT, Sugiaman VK, Pranata N: Comparison of antibacterial activity of both seeds and leaves ethanol extract of avocado (Persea americana Mill.) against Streptococcus mutans. MDJ. 2023; 12(1): 38–42. Publisher Full Text\n\nLiu S, Sun Y, Liu Y, et al.: Genomic and phenotypic characterization of Streptococcus mutans isolates suggets key gene clusters in regulating its interaction with Streptococcus gordonii. Front. Microbiol. 13: 945108. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCampos J, Pires MF, Sousa M, et al.: Unveiling the relevance of the oral cavity as a Staphylococcus aureus colonization site and potential source of antimicrobial resistance. Pathogens. 2023; 12(765): 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMontelongo-Jauregui D, Lopez-Ribot JL: Candida interactions with the oral bacterial microbiota. J. Fungi. 2018; 4(122): 1–15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSantosa CM, Rosyadi I, Arifianto D, et al.: Kajian kliniko-patologik dan antimikroba ekstrak biji alpukat (Persea americana Mill.). Jurnal Sain Veteriner. 2019; 37(2): 160–165. Publisher Full Text\n\nMorelli VG, Oliveira VC, Vasconcelos GLL, et al.: Effect of effervescent tablets on removable partial denture hygiene. Am. J. Dent. 2023; 36(2): 75–80. PubMed Abstract\n\nO’Brien TJ, Figueroa W, Welch M: Decreased efficacy of antimicrobial agents in polymicrobial environment. ISME J. 2022; 16: 1694–1704. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKart D, Tavernier S, Acker H, et al.: Activity of disinfectants against multispecies biofilms formed by Staphylococcus aureus, Candida albicans, and Psedomonas aeruginosa. Biofouling. 2014; 30(3): 377–383. PubMed Abstract | Publisher Full Text\n\nAnju VT, Busi S, Imchen M, et al.: Polymicrobial infections and biofilms: Clinical significance and eradication strategies. Antibiotics. 2022; 11(1731): 1–31. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOlson ML, Jayaraman A, Kao KC: Relative abundances of Candida albicans and glabrata in in vitro coculture biofilms impact and formation. Appl. Environ. Microbiol. 2018; 84(8): e02769–e02717. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrunke S, Hube B: Two unlike cousins: Candida albicans and C. glabrata infection strategies. Cell. Microbiol. 2013; 15(5): 701–708. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBernard C, Girardot M, Imbert C: Candida albicans interaction with gram-positive bacteria within interkingdom biofilms. J. Mycol. Médicale. 2020; 30(1): 1–8. PubMed Abstract | Publisher Full Text\n\nDiaz PI, Strausbaugh LD, Dongari-Bagtzoglou: Fungal-bacterial interactions and their relevance to oral health: linking the clinic and the bench. Front. Cell. Infect. Microbiol. 2014; 4(101): 1–6. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHu Y, Niu Y, Ye X, et al.: Staphylococcus aureus synergized with Candida albicans to increase the pathogenesis and drug resistance in cutaneous abscess and peritonitis murine models. Pathogens. 2021; 10(1036): 1–17. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGuo Y, Wei C, Liu C, et al.: Inhibitory effects of oral Actinomyces on the proliferation, virulence and biofilm formation of Candida albicans. Arch. Oral Biol. 2015; 60: 1368–1374. PubMed Abstract | Publisher Full Text\n\nMorse DJ, Wilson MJ, Wei X, et al.: Modulation of Candida albicans virulence in in vitro biofilms by oral bacteria. Lett. Appl. Microbiol. 2019; 68: 337–343. PubMed Abstract | Publisher Full Text | Free Full Text\n\nUruén C, Chopo-Ecuin G, Tommassen J, et al.: Biofilms as promoters of bacterial antibiotic resistance and tolerance. Antibiotics. 2021; 10(3): 1–36. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBatoni G, Maisetta G, Esin S: Therapeutic potential of antimicrobial peptides in polymicrobial biofilm-associated infections. Int. J. Mol. Sci. 2021; 22(482): 1–24. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVinha AF, Moreira J, Barreira SVP: Physicochemical parameters, phytochemical composition and antioxidant activity of algarvian avocado (Persea americana Mill.). J. Agric. Sci. 2013; 5(12): 100–109. Publisher Full Text\n\nGutiérrez-Venegas G, Gόmez-Mora JA, Meraz-Rodríguez MA, et al.: Effect of flavonoids on antimicrobial activity of microorganisms present in dental plaque. Heliyon. 2019; 5: e03013. Publisher Full Text\n\nMatilla-Cuenca L, Gil C, Cuesta S, et al.: Antibiofilm activity of flavonoids on staphylococcal biofilms through targeting BAP amyloids. Nat. Res. 2020; 10(18968): 18912–18968. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDennis, Nurliza C, Savitri W: Antibacterial effect of ethanol extract of the avocado seed (Persea americana Mill.) as an alternative root canal irrigants againts Porphyromonas gingivalis (in vitro). Int. J. App. Dent. Sci. 2017; 3(1): 89–93. 2394-7497.\n\nVillanueva X, Zhen L, Ares JN, et al.: Effect of chemical modifications of tannins on their antimicrobial and antibiofilm effect against Gram-negative and Gram-positive bacteria. Front. Microbiol. 2023; 13(987164): 1–15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYan Y, Li X, Zhang C, et al.: Research progress on antibacterial activities and mechanisms of natural alkaloids: A review. Antibiotics. 2021; 10(318): 1–30. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBrahim MAS, Fadli M, Markouk M, et al.: Synergistic antimicrobial and antioxidant activity of saponins-rich extracts from paronychia argentea and Spergularia marginata. European J. Med. 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}
|
[
{
"id": "320510",
"date": "03 Oct 2024",
"name": "Nada Z. Mohammed",
"expertise": [
"Reviewer Expertise Prosthetic dentistry",
"dental materials",
"Microbiology"
],
"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 Methods are concise, it needs to be more informative, add the name of tests used. -You should add a concise information about the statistical analysis that used in the study.\nIntroduction -The introduction is informative but lacks a clear statement of the research gap and aim of the research.\nMethods -The methodology section is detailed but could benefit from sequential numbering of the subheadings for better organization - There are many paragraphs without reference ; you should add the reference. - In Avocado seed extraction procedure ; Chromatography also should be carried out to identified the extract composition. - Mention the name of medium used to culture Actinomyces odontolyticus on fastidious anaerobe agar. - In Biofilm formation on heat polymerized acrylic resin disc ; How much the amount of polymicrobial biofilm was added. - Inhibition Value%=[(ControlOD_SampleOD)÷-ControlOD]×100; clarify if the subtracted control was the negative or positive ? -Statistical analysis required more clarification as mentioned by adding table for the inhibition value for each extract treatment group obtained by the inhibition formula to be compared directly\n\nResult -The results are presented clearly; but it could be improved; the results display need to be more consistent without excessively repeating the data. Display the main finding and explain the reason leads to this result -Please insert table contain the inhibition value obtained by the inhibition formula\nDiscussion -The authors should enrich the discussion by the analysis and interpreting the obtained results and by comparing the obtained results with what reported in other papers. -The limitations of the studies should be presented. -The clinical relevance should be further highlighted.\nTables -The MBIC50 of avocado seed extract and its effect on polymicrobial biofilm; the 50.81_8.32%. value must be placed in table.\nReferences There are too many references. Remove the outdated and unnecessary 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? 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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12673",
"date": "29 Oct 2024",
"name": "Thalia Angela",
"role": "Author Response",
"response": "First and foremost, we would like to thank the reviewers for providing necessary reviews to improve the content and writing of the articles. We have made changes in the new version of the article according to the reviews given. Reviewer comments and Angela et al. responses (R.) Abstract 1. The Methods are concise, it needs to be more informative, add the name of tests used. 2. You should add a concise information about the statistical analysis that used in the study R: We have included the name of the test (microtiter biofilm plate assay) and the statistical analysis used in the study as concise as possible. Introduction The introduction is informative but lacks a clear statement of the research gap and aim of the research. R: We have given a much clearer statements on the research gap and the research aim which can be seen on the last paragraph of the introduction section. Methods 1. The methodology section is detailed but could benefit from sequential numbering of the subheadings for better organization R: We have added sequential numbering on the methods section. 2. There are many paragraphs without reference; you should add the reference. R: We have added necessary references on the methods section. 3. In Avocado seed extraction procedure; Chromatography also should be carried out to identified the extract composition. R: We do agree that the extract can use Chromatography to further identify the extract composition. In our research location, the only available Chromatography is Gas Chromatography Mass Spectrometry (GC-MS). However, we decided not to do the test during our research period as we only wanted to know the presence of flavonoids, polyphenols, alkaloids, and saponin in our avocado seed extract as many research have shown their antimicrobial properties in order to make sure that we fulfilled the purpose of our study which is to know the effect of avocado seed extract on denture plaque microorganisms grown on HPA resin. The two tests we have done, phytochemical examination and its quantitative tests, have shown the existence of those compound and specified their amount in the extract. Hence, we directly continue our research without doing Chromatography. 4. Mention the name of medium used to culture Actinomyces odontolyticus on fastidious anaerobe agar. R: We have previously written the name of the medium used to culture A. odontolyticus which is fastidious anaerobe agar which we supplemented with 5% (v/v) defibrinated bovine blood. 5. In Biofilm formation on heat polymerized acrylic resin disc; How much the amount of polymicrobial biofilm was added. R: We have specified the amount of polymicrobial biofilm added which can be seen on the second subheading “Biofilm formation on heat polymerized acrylic resin disc” 6. Inhibition Value%=[(ControlOD_SampleOD)÷-ControlOD]×100; clarify if the subtracted control was the negative or positive? R: We confirmed that the ControlOD for the inhibition value formula is positive, not negative. 7. Statistical analysis required more clarification as mentioned by adding table for the inhibition value for each extract treatment group obtained by the inhibition formula to be compared directly R: We have added the inhibition value table on the Result section. Result 1. The results are presented clearly; but it could be improved; the results display need to be more consistent without excessively repeating the data. Display the main finding and explain the reason leads to this result R: We have removed the repetitive sentences. 2. Please insert table contain the inhibition value obtained by the inhibition formula R: We have replaced the figures of inhibition value into tables (Table 3 dan Table 5). Discussion 1. The authors should enrich the discussion by the analysis and interpreting the obtained results and by comparing the obtained results with what reported in other papers. R: We would like to apologize for our paper shortcoming. We have previously included as much other paper results as possible, however there is still limited data that can be used as comparison, especially for the microorganisms that we studied in this paper, such as C. glabrata, A. odontolyticus, S. gordonii. 2. The limitations of the studies should be presented. R: We have presented the limitations of the study and made a separate section for it. 3. The clinical relevance should be further highlighted. R: We have highlighted the clinical relevance which is written on the last sentence in the discussion section, above the study limitation. Tables The MBIC50 of avocado seed extract and its effect on polymicrobial biofilm; the 50.81_8.32%. value must be placed in table. R: We have added it to Table 5 in the results section. References There are too many references. Remove the outdated and unnecessary references R: We have removed the outdated and unnecessary references."
}
]
},
{
"id": "320506",
"date": "04 Oct 2024",
"name": "Mervat E. Abd-Ellah",
"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\nThe work being reviewed is entitled “ The effect of soaking heat-polymerized acrylic resin denture base in avocado seed extract on the inhibition of denture-plaque microorganisms biofilm growth”\n\nThis study aimed to evaluate the effect of avocado seeds on denture-plaque microorganism biofilm on Heat polymerized acrylic (HPA) resins. It was concluded that 20% avocado seed extract was effective in inhibiting polymicrobial biofilm because it was able to inhibit more than 50% polymicrobial biofilm.\n\nThere are certain limitations for approving this study;\n- First, it was mentioned that “The avocado seed powder was put into a vessel and poured with 70% ethanol solvent” then may be the antimicrobial effect from the ethanol not the avocado seed powder and that makes the idea of the study not sound.\n- Second, the work partly cite the current literature as it does not justify the use of the used concentrations of avocado seed extract clearly. It was mentioned that “Anggraini et al. (2017 [Ref - 1]) studied the inhibition zone of avocado seed extract at concentrations of 10%, 20%, 40%, 80%, 100% on the growth of C. albicans, and found that the 10% concentration was the most effective concentration in inhibiting C. albicans.22 Another study by Talib et al. (2018 [Ref - 2]) tested the effectiveness of avocado seed extract in inhibiting Streptococcus mutans at concentrations of 2%, 4%, 6%, 8%, 10% and found that the most effective concentration was 10%.23” It was already stated that 10% is the most effective concentration, then it was useless to test the same concentration that was used before. This is an unnecessary repetition. Moreover, it was concluded in the current study that 20% avocado seed extract was effective in inhibiting polymicrobial biofilm but it was not justified way the difference in percentage of avocado seed extract from the literature that stated that 10 % was the most effective concentration in inhibiting C. albicans\n- Third, it was mentioned that “Sterile HPA resin discs were preconditioned for 24 hours by immersion in artificial saliva.” You did not say how the process of sterilization happened. Please clarify.\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? 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 source data required\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12674",
"date": "31 Oct 2024",
"name": "Thalia Angela",
"role": "Author Response",
"response": "First and foremost, we would like to thank the reviewers for the reviews given to improve the content and writing of the articles. We have made the changes accordingly in the new version and we would also like to humbly respond to some of the reviews given. Reviewer comments and Angela et al. responses (R.) First, it was mentioned that “The avocado seed powder was put into a vessel and poured with 70% ethanol solvent” then may be the antimicrobial effect from the ethanol not the avocado seed powder and that makes the idea of the study not sound. R: We would like to explain the use of 70% ethanol solvent when it was poured inside the vessel containing the avocado seed powder. According to Abubakar et al. (2020), solvent is also known as menstruum which is defined as a liquid chosen for an effective extraction process.1 The solvent used in this study is ethanol which is a polar solvent that is used to extract polar compounds such as flavonoids and polyphenols. The reason we are using 70% ethanol (water-ethanol) instead of water only is that according to Plaskova et al. (2023), all the bioactive molecules from the plant material cannot be extracted using only single solvent, instead binary solvent mixture such as water and organic solvent are recommended. The study claimed that water-ethanol solvent shows a much better extraction of polyphenols than any single solvent.2 Another study that supported this claim is a study by Munthe et al. (2023) which concluded that 70% ethanolic extract of avocado seeds using maceration technique showed a strong antioxidant activity.3 In our study, at the end of extraction process, the filtered liquid avocado seed extract underwent evaporation on a rotary evaporator which removed the solvents used for extracting the avocado seeds, leaving behind a very thick extract. Plaskova et al. (2023) did mentioned that some residual solvents might remain unintentionally, however the level of the remaining solvent is limited. The study has also presented a table showcasing the maximum limitation of the solvent which can be further read in the published paper.2 The thick extract that our study has gained are then diluted using aquadest, hence the negative control of our study is also aquadest because it can be said that through the evaporation process, the ethanol solvent has little to no effect in contributing to the antimicrobial effect. References Abubakar AR, Haque M. Preparation of medicinal plants: basic extraction and fractionation procedures for experimental purposes. J Pharm Bioallied Sci. 2020;12(1):1-10. doi: 10.4103/jpbs.JPBS_175_19 Plaskova A, Mlcek. New insights of the application of water or ethanol-water plant extract rich in active compounds in food. Front Nutr. 2023;10:1118761. doi: 10.3389/fnut.2023.1118761 Munthe SWN, Riskianto R, Juvi D, Novia J. Antioxidant, total phenolic, and total flavonoid of 70% ethanol extract of avocado seeds (Persea americana Mill.). Pharmacogn J. 2023;15(4):599-605. doi: 10.5530/pj.2023.15.126 Second, the work partly cite the current literature as it does not justify the use of the used concentrations of avocado seed extract clearly. It was mentioned that “Anggraini et al. (2017 [Ref - 1]) studied the inhibition zone of avocado seed extract at concentrations of 10%, 20%, 40%, 80%, 100% on the growth of C. albicans, and found that the 10% concentration was the most effective concentration in inhibiting C. albicans.22 Another study by Talib et al. (2018 [Ref - 2]) tested the effectiveness of avocado seed extract in inhibiting Streptococcus mutans at concentrations of 2%, 4%, 6%, 8%, 10% and found that the most effective concentration was 10%.23” It was already stated that 10% is the most effective concentration, then it was useless to test the same concentration that was used before. This is an unnecessary repetition. Moreover, it was concluded in the current study that 20% avocado seed extract was effective in inhibiting polymicrobial biofilm but it was not justified way the difference in percentage of avocado seed extract from the literature that stated that 10% was the most effective concentration in inhibiting C. albicans. R: We would like to explain the reason why we included those previous studies in our Introduction section and why we did our research based on the concentrations that the previous studies have concluded. Denture plaque that is formed in the denture wearers appliances is not a mono-species biofilm but a polymicrobial one. O’Donnell et al. (2015) declared that denture plaque consists of Candida spp. which co-aggregates with bacteria.1 The previous studies we included in our paper are only done on planktonic bacteria and fungal, not polymicrobial biofilm. Meanwhile a study by Hamzah et al. (2019) has found that a much higher concentration is needed to inhibit polymicrobial biofilm than mono-species biofilms. Not to mention, the previous studies we included our papers are done on C. albicans and S. mutans while our paper actually studies the effect of avocado seed on C. albicans, C. glabrata, A. odontolyticus, S. gordonii, S. aureus, both mono-species and polymicrobial biofilms. Hence, our study still used the previous established effective concentration (10%) with varieties that centered on the concentration from previous studies (5%, 15%, 20%).2 We also still studied the effect of avocado seed on the mono-species biofilms to not only know which concentration can be determined as the MBIC50 on each mono-species biofilms, but also to see whether there is truly a difference between the MBIC50 of each mono-species biofilm and the polymicrobial biofilm. The result of our study, which summary can be seen on our Abstract section, has shown that MBIC50 for each mono-species are different from the previous studies’ concentration. This shows that our study did not do any unnecessary repetition. On a side note, we have added further explanation on the research gap in our introduction section. We hope it could add more clearance on the matter. We truly appreciate the feedback given by the reviewer. References O’Donnell LE, Robertson D, Nile CJ, et al.: The oral microbiome of denture wearers is influenced by levels of natural dentition. PLoS One. 2015;10(9):e0137717. 26368937 10.1371/journal.pone.0137717 PMC4569385 Hamzah H, Hertiani T, Pratiwi SUT, et al.: The inhibition activity of tannin on the formation of mono-spesies and polymicrobial biofilm Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Trad. Med. J. 2019;24(2):110–118. 10.35856/mdj.v7i1.12 Third, it was mentioned that “Sterile HPA resin discs were preconditioned for 24 hours by immersion in artificial saliva.” You did not say how the process of sterilization happened. Please clarify. R: We have clarified the sterilization process of the HPA resin discs in the Methods section."
}
]
},
{
"id": "320505",
"date": "29 Oct 2024",
"name": "Prabha S Newaskar",
"expertise": [
"Reviewer Expertise Prosthodontics",
"Dental materials",
"Implants",
"Maxillofacial prosthodontics",
"Systematic reviews",
"Fixed prosthodontics",
"Removable prosthodontics."
],
"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 current in-vitro study is based on denture plaque microorganism inhibition by avocado seed extract on heat-cured denture base resin. The author considered the 5%, 10%, 15% & 20% concentrations of the same extract and two groups of controls. for the study. and concluded that a 20% concentration was more effective than other concentrations. The following are suggestions for improvement of the current manuscript: 1. Abstract: Ensure that the abstract concisely summarizes the key findings. The methodology, key results, and conclusion can be streamlined further to highlight the core contributions without too much technical detail. 2. Methodology: Include any steps taken to mitigate bias or ensure reproducibility. For instance, if there were any controls (such as positive and negative controls), clearly define how they were handled to ensure the integrity of the experiment. Specify more details about the process of ensuring the sterility of HPA resin disks or provide a brief explanation of the significance of the preparation technique. 3. Result: Add more visual aids (tables, charts, or graphs) to clarify results. This will make it easier for readers to interpret the data. provide context to the statistical findings. Instead of just reporting p-values, discuss the biological or practical significance of these results. 4. Discussion: Ensure that each point is directly tied back to the research question. Avoid over-explaining background information already provided in the introduction. Provide a more detailed comparison between your findings and previous studies. Highlight areas where your results diverge or align with other research to emphasize the novelty or contribution of your work. 5. Conclusion: You may consider discussing the potential limitations of your study (e.g., the in vitro setting) and suggest avenues for future research. 6. Reference & citations: Double-check all citations to ensure they adhere to the journal's guidelines (e.g., proper format, all sources accounted for). Ensure recent and relevant literature is cited, particularly on the antimicrobial activity of avocado seed extracts. 7. Ethical consideration: If the study involves the handling of microorganisms, briefly outline the safety measures taken to ensure proper disposal and handling, in compliance with biosafety standards. 8. Language & grammar: Revise for grammatical consistency. For instance, avoid shifting tenses within the same section. Avoid redundancy. For example, once the MBIC50 is defined, you do not need to explain it repeatedly in different sections.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-933
|
https://f1000research.com/articles/13-1292/v1
|
29 Oct 24
|
{
"type": "Research Article",
"title": "Computational prediction of a phage cocktail active against multidrug-resistant bacteria",
"authors": [
"Rabia Nawaz",
"Ali Husnain",
"Muhammad Ali Arif",
"Zohal Hassan",
"Ammara Ahad",
"Hafsa Amat Ur Rasool",
"Muhammad Shahid",
"Uqba Mehmood",
"Attia Razzaq",
"Muhammad Idrees",
"Wayne G.Carter",
"Rabia Nawaz",
"Ali Husnain",
"Muhammad Ali Arif",
"Zohal Hassan",
"Ammara Ahad",
"Hafsa Amat Ur Rasool",
"Muhammad Shahid",
"Uqba Mehmood",
"Attia Razzaq",
"Muhammad Idrees"
],
"abstract": "Background Antibiotic misuse and overuse have contributed to the emergence of multi-drug resistant (MDR) bacteria, posing a serious public health problem across the globe. Phage cocktails, which combine multiple phages, provide an efficient method to combat multidrug-resistant bacterial infections. This study integrated a computational pipeline to design a phage cocktail against the bacterial strains Acinetobacter baumannii AB0057, Klebsiella pneumoniae subsp. pneumoniae HS11286, and Pseudomonas aeruginosa UCBPP-PA14.\n\nMethods The whole genome sequences of selected multidrug-resistant bacteria were accessed. Prophage sequences were identified from them which could be expressed to produce viable lytic phages against MDR bacterial strains, thereby reducing the severity of infection. Prophages were annotated for open reading frames (ORFs), putative promoters, virulence factors, transcriptional terminators, ribosomal RNAs, and transfer RNAs. A dot plot was also generated to investigate similar phages and phylogenetic analysis was performed.\n\nResults A total of 11 prophages were predicted from the bacterial genomes. About 472 open reading frames were predicted along with 3 transfer RNAs. Additionally, the presence of 754 putative promoters and 281 transcription terminator sequences was also detected. Comparative genomic and phylogenetic analyses provided insight into the diversity, relatedness, and lytic potential of the phages. The final designed phage cocktail consisted of five selected prophages including Acinetobacter baumannii prophages (2759376-2809756) and (3311844-3364667), and Klebsiella pneumoniae prophages (1288317-1338719), (1778306-1808606), and (2280703-2325555).\n\nConclusion The phage cocktail designed in this study might be useful against MDR Acinetobacter baumannii and Klebsiella pneumoniae infections, especially where conventional antibiotics fail. Sequence similarity analysis suggested that the phage cocktail may also be effective against other carbapenemase-producing K. pneumoniae strains.",
"keywords": [
"Acinetobacter baumannii",
"Klebsiella pneumoniae",
"MDR bacteria",
"Prophage annotation",
"Prophage detection"
],
"content": "1. Introduction\n\nAntibiotic resistance is a major public health concern worldwide (World Health Organization, 2023). Multidrug-resistant (MDR) bacterial infections are challenging to treat as these bacteria have developed resistance to a variety of conventional drugs. Overuse and misuse of antibiotics in both humans and livestock is a major factor that has contributed to the creation and spread of antibiotic-resistant bacteria (World Health Organization, 2023; Mittal et al., 2020). MDR infections in humans result in a wide range of diseases, including skin infections, pneumonia, sepsis, and urinary tract infections. These infections can be difficult to treat, leading to longer hospital stays, higher healthcare costs, and a higher mortality risk. The number of MDR infections is increasing globally, and in some severe cases, there are no viable or effective treatments available (Chinemerem et al., 2022).\n\nPhage therapy utilizes viruses that selectively target and infect bacterial cells. This highly specific approach offers an effective alternative to antibiotics for the treatment of bacterial infections, without causing harm to eukaryotic cells. People in Eastern Europe and the former Soviet Union have used phage therapy to treat bacterial infections, with treatments initiated nearly a century ago (Chanishvili, 2012). In recent years, phage therapy has received interest as a potential solution to the problem of antibiotic resistance and phage cocktails with selective bacteriophages provide a promising strategy for treating infections caused by MDR bacterial strains (Yen et al., 2017; Michodigni et al., 2022).\n\nThe carbapenem-resistant strains of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa are among the globally prevalent MDR bacteria that have caused bacterial outbreaks (Buehrle et al., 2017; Hamidian & Hall, 2011). Carbapenem-resistant Pseudomonas aeruginosa can cause pneumonia and bacteremia in infected subjects (Wen et al., 2018). Based on their clinical significance, these bacteria have been selected as targets for phage cocktail-based bacteriophage therapy (Adams et al., 2008; Cienfuegos-Gallet et al., 2022; Aly et al., 2008).\n\nProphages are the genomes of bacteriophages that are integrated into the chromosomes of host bacteria. Prophages remain dormant until they express their genomic regions in order to initiate a lytic cycle. They serve as a reservoir of genes that are required for the expression of structural and functional viral components that produce an active bacteriophage (Fortier and Sekulovic, 2013; Premetis et al., 2023). This study considered a phage cocktail creation that could tackle certain MDR bacteria. Instead of considering individual phages, a phage cocktail design was undertaken that contained a mixture of selected phages since this represents a potentially viable method for targeting a broader range of MDR bacterial strains.\n\n\n2. Methods\n\nThree whole genome sequences of bacteria were selected based on their pathogenicity in humans and generation of MDR diseases. The NCBI GenBank was used to obtain the nucleotide sequences of Acinetobacter baumannii AB0057 (accession number: NC_011586.1), Klebsiella pneumoniae subsp. pneumoniae HS11286 (accession number: NC_016845.1), and Pseudomonas aeruginosa UCBPP-PA14 (accession number: NC_008463.1).\n\nThe presence of prophages in the genomes of Acinetobacter baumannii AB0057, Klebsiella pneumoniae subsp. pneumoniae HS11286, and Pseudomonas aeruginosa UCBPP-PA14 were investigated by utilizing the results of prophage prediction from a previous study conducted by Mageeney et al. (2020a). In this study, prophage prediction was performed using two bioinformatics software programs: Islander (Hudson et al., 2015) and TIGER (Mageeney et al., 2020b). The predicted prophages were extracted from the output files generated by these tools and were used for further analyses. In addition, the PHASTER tool (Arndt et al., 2016) was also used to identify potential prophages in the selected bacterial genomes.\n\nOpen reading frames encoded by the 11 selected prophage sequences were predicted by two command line tools Prodigal Hyatt et al., 2010) and Phanotate McNair et al., 2019), and an online tool GeneMark.hmm (Besemer et al., 2001).\n\nThe Prokka annotation tool (Seemann, 2014) was utilized to locate the transfer RNAs, CDS, and ribosomal RNAs from the predicted prophages. In order to determine the locations of genomic features inside contigs, Prokka uses external feature prediction algorithms.\n\nPredicted ORFs were annotated using the BLASTP algorithm against the non-redundant (nr) protein database of the NCBI (National Center for Biotechnology Information).\n\nThe putative promoter sequences and regions on the phage genomes were identified using BPROM which is a promoter online analysis tool of Softberry (Salamov and Solovyev, 2011).\n\nVirulent genes on the predicted prophage sequences were detected by using the VFDB: Virulence Factor Database.\n\nRho-independent transcription terminators on predicted prophage sequences were detected using ARNold program (Naville et al., 2011).\n\ntRNAs carried by prophage sequences were detected using the online program tRNAscan-SE (Schattner et al., 2005) and ARAGORN. The rRNA genes were also searched using Barrnap ribosomal RNA predictor.\n\nA dot plot was generated using Gepard software in order to check the similarity between sequences of prophages (Krumsiek et al., 2007).\n\nTo identify the phages with the highest similarity, Blastn analysis was performed against a standard database of nucleotides within NCBI.\n\nComparative genome analysis of predicted prophages was conducted using EasyFig 2.2 (Sullivan et al., 2011). Genome maps of selected prophage sequences were constructed with their highest similar lytic phages using the tBlastx analysis and with a minimum selected e-value of 0.001.\n\nPhylogenetic analysis of the selected phages was performed based on the nucleotide sequences of their large terminase subunits. A neighbor-joining phylogenetic tree was constructed for nucleotide sequences of finally selected prophages using MEGA 11 software with 1000 bootstrap replications (Tamura et al., 2021).\n\n\n3. Results\n\nThe detection of the presence and then annotation of prophages within bacterial genomes was undertaken. Similar to the study of Mageeney et al. (2020b), 7 prophages from Klebsiella pneumoniae subsp. pneumoniae HS11286, 3 prophages from Acinetobacter baumannii AB0057, and 1 prophage from Pseudomonas aeruginosa UCBPP-PA14 were detected using islander and TIGER algorithms. The island length and coordinates of these predicted prophages were determined and have been included in Table 1. Subsequently, whole genome sequences of Acinetobacter baumannii AB0057, Pseudomonas aeruginosa UCBPP-PA14, and Klebsiella pneumoniae subsp. pneumoniae HS11286 were retrieved from NCBI (accession numbers “NC_011586.1”, “NC_008463.1” and “NC_016845.1”, respectively) and prophage prediction undertaken using the PHASTER tool (Table 2).\n\nAbout 29 ORFs were predicted from Acinetobacter baumannii AB0057 prophages (1464206-1483241), 79 ORFs from Acinetobacter baumannii AB0057 prophages (2759376-2809756), and 85 ORFs from Acinetobacter baumannii AB0057 prophages (2759376-2809756). Only 14 ORFs were predicted from Pseudomonas aeruginosa UCBPP-PA14 prophage (4345129-4355794). There were 14, 13, 73, 37, 63, 43, and 22 ORFs predicted from 7 Klebsiella pneumoniae subsp. pneumoniae HS11286 prophages (Table 3) and their positions, strand type and length of gene were also annotated (Underlying data: ORFs) (Nawaz, 2024).\n\nThe BLASTP algorithm was used to annotate ORFs in the prophage sequences of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The sequences were compared with known protein sequences in the NCBI non-redundant protein database, and where possible, putative functions and biological roles were assigned (Underlying data: BLASTp_analysis) (Nawaz, 2024). A total of 29, 79, and 85 ORFs were identified in 3 prophages of Acinetobacter baumannii with maximum protein sequence identity percentages of 100% and minimum identity percentages ranging from 30.84 to 42.82%. Similarly, 14, 13, 73, 37, 63, 43, and 22 ORFs were identified in 7 prophages of Klebsiella pneumoniae with maximum protein sequence identity percentages of 100% and minimum identity percentages ranging from 27.51 to 93.83%. Finally, 14 ORFs were identified in 1 prophage of Pseudomonas aeruginosa, with maximum protein sequence identity percentages of 100% and minimum identity percentages of 38.22%. ORFs with their maximum and minimum identities were also predicted (Table 4).\n\nAnnotations of prophages revealed the coding sequences (CDS) and tRNAs carried by the prophage sequences. One tRNA was found from Acinetobacter baumannii AB0057 prophage (3311844-3364667) and two tRNAs from Klebsiella pneumoniae subsp. pneumoniae HS11286 prophage (1288317-1338719). However, no ribosomal RNAs were found in the prophage sequences (Table 5).\n\nThe three prophages of Acinetobacter baumannii had 47, 126, and 133 putative promoters, respectively. Among the seven prophages of Klebsiella pneumoniae, the number of putative promoters were 25, 19, 108, 67, 95, 78 and 37. For the single prophage of Pseudomonas aeruginosa, 19 putative promoters were identified (Table 3). The list of promoter sequences of 11 prophages with their transcription factors (TFs), binding site, position and binding scores were recorded (Underlying data: Promoter_sequences) (Nawaz, 2024).\n\nThe expression of virulent genes produces bacterial virulence factors, which have an essential role in bacterial pathogenicity (Abdulateef et al., 2023), hence, it is important to check for their existence in prophage sequences prior to prophage final selection. The prediction analysis identified peptidoglycan DD-metalloendopeptidase family protein and undecaprenyl-phosphate glucose phosphotransferase in one prophage sequence from Klebsiella pneumoniae, which are known virulence factors (Paczosa & Mecsas, 2016). Additionally, the prophage of Pseudomonas aeruginosa was found to contain phenazine biosynthesis protein PhzF, which is involved in phenazine biosynthesis and has been linked to virulence in P. aeruginosa (Blankenfeldt & Parsons, 2014) (Table 6).\n\n† Prophage size less than 30 kb.\n\n‡ Values that did not meet the inclusion criteria.\n\nRho-independent transcriptional termination in bacteria is characterized by the formation of a G/C rich hairpin structure which efficiently terminates transcription elongation without the requirement for a Rho-factor. The prediction of Rho-independent terminators is required to understand the transcriptional regulation of prophage genes and their integration into the host genome (Naville et al., 2011). Sequence analysis showed the presence of various Rho-independent transcription terminators in prophages, including 3 prophages of Acinetobacter baumannii containing 18, 53, and 61 terminators, 7 prophages of Klebsiella pneumoniae containing 10, 8, 35, 25, 31, 29, and 9 terminators, and 1 prophage of Pseudomonas aeruginosa containing 2 terminators (Table 3). The predicted transcription terminators, the position of terminators in the prophage genome, strand type, and the sequence of predicted terminators were also recorded (Underlying data: Terminators_sequences) (Nawaz, 2024).\n\ntRNAs prediction was undertaken using tRNA-SCAN-SE and ARAGORN programs and these detected the presence of 3 tRNA regions in the 11 prophage genomes (Table 5). Given that the host bacteria normally supply the tRNA molecules required for translation, this result raises the possibility that these prophages rely on the host translation machinery for protein synthesis. The structure of the tRNAs was also predicted (Figure 1a, b). Barrnap was used to attempt the detection of rRNA genes from the prophage sequences, but none were detected.\n\nA dot plot, created using Gepard software, provided a means to investigate the similarity between sequences of the selected Acinetobacter baumannii AB0057 and Klebsiella pneumoniae subsp. pneumoniae HS11286 prophages (Figure 2). In order to avoid redundancy, the Klebsiella pneumoniae subsp. pneumoniae HS11286 prophage (1778306-1808606) was rejected from further consideration, as its sequence was found to be highly similar to that of Klebsiella pneumoniae subsp. pneumoniae HS11286 prophage (4049881-4085225).\n\nFor the selection of viable phages, the threshold values for annotations including prophage size, presence of any tRNAs, rRNAs, virulence factors, terminators and promoter regions, and sequence similarity analysis were taken into consideration. The prophages having sequence length less than 30 kb, those sharing sequence similarity with other prophages, or having any potential virulence factors were excluded from further study. Finally, based on the above-mentioned criteria, two out of three prophages from Acinetobacter baumannii AB0057 and three out of seven prophages from Klebsiella pneumoniae subsp. pneumoniae HS11286 were selected as viable phages (Table 6).\n\nComparative genome analysis of the 5 prophages with their highest similar lytic phage sequences were analysed using EasyFig 2.2. A multiple sequence alignment between our predicted prophage sequences and similar prophages was performed. A visual representation was produced showing linear comparisons for the similarities and differences between the prophages and their closest homologs. The genome map of Acinetobacter baumannii prophage (2759376-2809756) and Acinetobacter phage YC#06 (ON391949.1) indicated a similarity of 95.67% (Figure 3a), while A. baumannii prophage (3311844-3364667) with Acinetobacter phage Acba_3 (OQ101248) showed a similarity of 99.86% (Figure 3b). A higher similarity of 100% was indicated in the genome maps constructed for Klebsiella pneumoniae prophage (1288317-1338719) with Phage LAU1 (MN688132.1) (Figure 4a) and Klebsiella pneumoniae prophage (1778306-1808606) with Klebsiella phage ST437-OXA245phi4.2 (NC_049449.1) (Figure 4b). The genome map of Klebsiella pneumoniae prophage (2280703-2325555) with the highest similar Klebsiella phage ST11-VIM1phi8.3 (MK416019.1) showed a similarity of 99.99% (Figure 4c).\n\nBLASTn analysis was performed using 5 selected prophages. The most identical phages were selected for further analysis to check the viability and lytic potential of the prophages. The sequence similarity between two prophages of Acinetobacter baumannii and previously known phage sequences ranged from 93 to 99%, and for the three prophages of Klebsiella pneumoniae, it ranged from 80 to 100%. The identical phages, sharing 99.9% and 100% similarity with our prophages, were found to have been previously used in phage therapy (Jeon et al., 2012; Bagińska et al., 2023; Lavigne et al., 2004). The sequences of identical phages were retrieved via their accession numbers (Table 7).\n\n† The phages sharing 100 and 99.9% similarities and a query coverage between 78-89%.\n\nPhylogenetic analysis of predicted prophages was conducted based on their large terminase subunits. A neighbour-joining phylogenetic tree was generated with 1000 bootstrap replications using MEGA 11 (Figure 5). Phylogenetic analysis of the selected prophages along with the similar phages provided an insight into their diversity and relatedness. The Klebsiella pneumoniae prophages were present with other known Klebsiella pneumoniae phages showing close relatedness, whereas the prophages from Acinetobacter baumannii AB0057 sequences were closely related in a monophyletic order.\n\n\n4. Discussion\n\nA prophage is a phage genome incorporated into the genome of bacteria that can infect and destroy a bacterial cell once it is expressed (Fortier and Sekulovic, 2013; Premetis et al., 2023). The presence of potentially useful and exploitable prophages within a bacterial genome can be detected and annotated via metagenomic data mining and bioinformatic algorithms and tools. Hence, this study considered the identification and annotation of prophage sequences that have been integrated into the genomes of MDR bacterial strains. After conducting rigorous screening based on annotations and sequence similarity analyses, we detected five prophages which met various selection criteria for an ideal infective prophage. From this selection, a cocktail of phages was computationally designed, consisting of phages that could collectively target the MDR strains of Acinetobacter baumannii and Klebsiella pneumoniae. Each phage in the cocktail is selected for its ability to target specific MDR strains of Acinetobacter baumannii and Klebsiella pneumoniae. By using a combination of phages, the intention is that the cocktail will have improved effectiveness as a treatment since it can target multiple bacterial strains and potentially reduce the probability of resistance development, thereby enhancing overall therapeutic efficacy.\n\nAntibiotic resistance has propagated due to factors including the overuse or misuse of antibiotics, gene transfer, and inadequate diagnostics (World Health Organization, 2023; Mittal et al., 2020; Chinemerem et al., 2022; Ventola, 2015). Antibiotic-resistant bacteria like carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, have become an issue of global concern. These gram-negative bacteria are difficult to treat and the infections they cause often lead to increased morbidity and mortality rates (Breijyeh et al., 2020). Previous studies have considered the whole genome analysis of carbapenem-resistant Klebsiella pneumoniae genomes and MDR Acinetobacter baumannii; bacterial strains that can cause serious human health problems (Adams et al., 2008; Cienfuegos-Gallet et al., 2022). Phage therapy utilizes viruses which can attack and infect bacterial cells and can, therefore, operate as an effective substitute for antibiotics due to their high specificity and ability to target bacterial cells without harming human cells (Adams et al., 2008). Hence, bacteriophages are potential bactericidal agents; advantageous for the treatment of drug-resistant gram-negative bacteria (Breijyeh et al., 2020). Phage cocktails can be formulated by the combination of several phages that collectively possess an enhanced efficiency to lyse bacterial cells and can also be re-tailored if resistance develops (Abdulateef et al., 2023; Menor-Flores et al., 2022). This study considered the design of an effective phage cocktail against the MDR bacterial strains: Acinetobacter baumannii AB0057, Klebsiella pneumoniae HS11286, and Pseudomonas aeruginosa UCBPP-PA1, using a computational pipeline. Previously, therapeutic phage cocktails have been designed against Staphylococcus and Vibrio cholerae (Yen et al., 2017; Kornienko et al., 2020). Resistance to the antibiotic carbapenem is known to be dominant in the bacterial strains we have considered (Hamidian & Hall, 2011; Wen et al., 2018; Ranquet et al., 2001; Bi et al., 2015).\n\nPreviously, a number of integrative genetic elements including prophage sequences were identified in bacterial genomes using TIGER and Islander software, including 7, 3, and 1 prophage from the genomes of Klebsiella pneumoniae HS11286, Acinetobacter baumannii AB0057, and Pseudomonas aeruginosa UCBPP-PA1, respectively (Mageeney et al., 2020b). In the present study, we used the identified prophage sequences and considered their functional annotations. In addition, we examined prophage sequences from the selected strains using the PHASTER tool (Arndt et al., 2016) and this correlated with the prophage detection results of Mageeney et al. (2020b).\n\nA range of bioinformatic packages provide a means to reveal phage genomic data; with PHASTER, Prophet, Virsorter, PhiSpy and Phigaro algorithms utilized for identifying phages in Lactobacillaceae (Happel et al., 2022). Using this approach, prophage sequences that were beyond the average size range for bacteriophages in the NCBI Caudovirales database (less than 11.6 kb) were detected (Happel et al., 2022). Those prophages were excluded from further consideration since it was improbable that they would perform their function properly. Also, phages with a size larger than 800 kb, much larger than the size of known phage genome sizes, were excluded (Happel et al., 2022). Similarly, vertically inherited caudophage sequences have previously been detected in enterobacterial genomes, whilst discarding phages with a size lower than 30 kb, considering them to be non-functional (Bobay et al., 2014). Hence, in this study, we selected only those prophages with a size greater than 30 kb for cocktail design, and none were larger than 60 kb; indicative of prophages that can code for complete and viable bacteriophages.\n\nA total of 472 ORFs were predicted from the 11 prophages analyzed. We used the BLASTP algorithm to annotate the predicted ORFs in the prophage genomes. The NCBI non-redundant protein database which contains known protein sequences was then used to consider putative functions and potential biological roles of the encoded proteins. A total of 193 ORFs in 3 prophages of Acinetobacter baumannii were identified with maximum identity percentages of 100% and minimum identity percentages of 30.84%, 40.68%, and 42.82%, respectively. The Acinetobacter phage 5W, effective against MDR Acinetobacter baumannii (Peng et al., 2022), was found to share high sequence similarity with our putative prophages. About 265 ORFs in 7 prophages of Klebsiella pneumoniae were identified with maximum percentage identities of 100% and minimum identity percentages of 93.76%, 27.51%, 87.79%, 93.83%, 59.29%, 70.18%, and 86.84%, respectively. A BLAST analysis of Klebsiella prophages showed sequence similarity with the Klebsiella phage Mulock. The Klebsiella phage KPP5665-2 and Klebsiella phage Mulock have been previously used for bacteriophage therapy against resistant strains of Klebsiella (Herridge et al., 2020). A total of 14 ORFs were identified in the prophage of Pseudomonas aeruginosa which showed maximum identity of 100% and minimum identity of 38.22% in BLAST analyses. We found that Pseudomonas phage Pf1 was the most identical, which is known to be effective against other Pseudomonas strains (Peng et al., 2022).\n\nProkka annotation of these prophages enabled us to acknowledge their features including coding sequence (CDS) regions, ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs). This annotation provided insight into the diversity and development of these mobile genetic elements, as well as their possible interactions with bacterial hosts and other mobile genetic elements. We also identified putative promoter sequences and regions in the 11 prophage genomes. Our study revealed that three prophages of Acinetobacter baumannii had 47, 126, and 133 putative promoters, respectively. Among the 7 prophages of Klebsiella pneumoniae, the number of putative promoters ranged from 19 to 108. For the single prophage of Pseudomonas aeruginosa, we identified 19 putative promoters. These findings provide insights into the potential regulatory mechanisms of these prophages and their interactions with their host bacteria.\n\nVirulent genes encode for virulence factors, crucial for the spread of bacterial infection and the potential initiation of disease. These factors also aid bacteria in the evasion of host defences, enhancing their pathogenicity (Abdulateef et al., 2023). Thus, in order to prevent bacteriophage-mediated transmission of these virulence genes, we used the Virulence Factor Database (VFDB) to detect them in our prophage genomic sequences. The results revealed that one prophage of Klebsiella pneumoniae harboured a peptidoglycan DD-metalloendopeptidase family protein and an undecaprenyl-phosphate glucose phosphotransferase, encoded by the wcaJ gene included in the cps gene cluster. This virulence factor is involved in the glycosyltransferase activity in the bacterial capsule (Paczosa & Mecsas, 2016). Additionally, the prophage of Pseudomonas aeruginosa was found to contain the phenazine biosynthesis protein PhzF, which is an isomerase that has been linked to virulence in P. aeruginosa (Blankenfeldt & Parsons, 2014). Thus, prophages in which these virulence genes were detected were rejected.\n\nThe Rho-independent transcriptional termination in bacteria involves the formation of a G/C rich 8-10 bp hairpin structure, followed by a uridine-rich stretch at the 3´ end of mRNA (Naville et al., 2011). This form of termination does not require the Rho factor and is adequate to trigger transcription arrest. This mechanism is characterized by sequence and structural signals within the genome, which can be identified via computational algorithms (Naville et al., 2011; Kingsford et al., 2007; Di Salvo et al., 2019). The detection of Rho-independent terminators is an important step in the annotation of phage genetic sequences as it characterizes the 3´ terminus of the mRNA transcript. We used ARNold program for the rapid identification of Rho-independent transcription terminators in our prophage sequences (Table 3).\n\nThe presence of 3 tRNAs encoded by 11 prophages was discovered through examination of the tRNA regions in the prophage genomes. Given that the host bacteria normally supply the tRNA molecules required for translation (Hudson et al., 2015), this result suggests that these prophages rely on the host translation machinery for protein synthesis. We also attempted to detect rRNA genes, which can interact with the host cell translation and protein production machinery. However, no rRNA genes were detected in the predicted prophages, but this does not have any effect on phage functioning because a bacteriophage hijacks the host translation machinery and replicates inside the host cell (Hamidian et al., 2019). A dot plot of selected phages was generated, which enabled us to reject K. pneumoniae prophage (4049881-4085225) which shared high sequence similarity with the K. pneumoniae prophage (1778306-1808606).\n\nSmall prophages with sizes below 11 kb, are considered to be non-functional and unable to assemble into a mature and viable bacteriophage, and only an intact phage with complete functional units can completely disrupt a target bacterium (Happel et al., 2022). The prophages with a size below 30 kb are also considered small, and it is difficult to differentiate between them and other mobile genetic elements (Bobay et al., 2014). This can pose a challenge when attempting to accurately identify and classify small prophages within prokaryotic genomes, therefore, we included only those prophages in our study which had a size greater than 30 kb.\n\nA comparative genome analysis of the prophages was conducted using EasyFig and genome maps were created to consider the similarities between two identical genomes of prophages. The selected prophages with the highest similar phage sequences were analyzed using EasyFig 2.2. This provided a visualization of the similarities and differences between the prophages and their closest homologs. The identified prophage Acinetobacter baumannii (2759376-2809756) shared 96.57% sequence similarity with Acinetobacter phage YC#06; a virulent Acinetobacter phage YC#06 (accession number: ON391949.1) active against MDR Acinetobacter baumannii 4015, that was previously identified and characterized for formulating a phage-antibiotic combination therapy in vitro (Luo et al., 2022).\n\nAfter performing BLASTn analyses, we reviewed available studies on phages having 100% and 99.9% similarity and a good query coverage with the prophages that we had detected and considered their ability to target any additional bacterial species or strains in addition to the aforementioned strains. We found that our selected prophage Acinetobacter baumannii 2759376-2809756 shared 96.06% identity with Podoviral Bacteriophage YMC/09/02/B1251 ABA BP (NC_01954.1) up to a query coverage of 40%. This bacteriophage belongs to the family Podoviridae and has a double-stranded circular DNA genome with a length of ~45kb and a 39.05% GC content. A complete analysis of Bacteriophage YMC/09/02/B1251 ABA-BP reported that this phage could lyse an isolate of the carbapenem-resistant Acinetobacter baumannii (CRAB) strain from a septic patient (Jeon et al., 2012). Previously, phages targeting a wide range of Klebsiella strains have also been reported, among which some of the phages were also included in our study. The phage (MK416019.1) was found to target K. pneumoniae ST11-VIM1 and phage (MK433582.1) was found to target K. pneumoniae ST258-KPC3. In the same way, phages (MN166823.1 and NC_049452.1) were reported to target K. pneumoniae ST512-KPC3 and phage (NC_049449.1) targets K. pneumoniae ST437-OXA245 (Bagińska et al., 2023; Lavigne et al., 2004). These Klebsiella strains are carbapenemase producing and can contribute to nosocomial infections, pneumonia, and urinary tract infections (Bleriot et al., 2020). These previously identified prophages shared a good percentage identity with our prophage sequences and this investigation suggested that the phage cocktail we have designed might target the above-mentioned bacterial strains as well, in addition to our selected MDR bacterial strains.\n\nA study on the determination of morphology and biological properties of 12 viable phages against MDR Acinetobacter baumannii was carried out previously, and these were further selected to be used against MDR Acinetobacter baumannii (Bagińska et al., 2023). BLAST analysis revealed that their selected phages shared sequence similarity with the phages detected against Acinetobacter baumannii in our study. Another study involved genomic analysis of 40 Klebsiella prophages which were integrated into 16 strains of carbapenem-resistant Klebsiella pneumoniae (Bleriot et al., 2020). They also included prophages, with high similarity to the Klebsiella pneumoniae prophages reported in the current study, and these phages contain proteins mainly involved in the structure of virions, replications, the transcription of virions, and the regulation of the lysogenic and lytic cycles (Bleriot et al., 2020).\n\nIn this study, we have selected a total of 5 prophages for designing a phage cocktail, following rigorous screening (Table 7). Phylogenetic analysis of prophages isolated from Acinetobacter baumannii and Klebsiella pneumoniae was performed using a neighbor-joining method and the sequences were selected based on BLASTn analyses. Prophage sequences with the highest similarity were selected and a phylogenetic tree was constructed based on large terminase subunits of selected phages. Two critical tasks are carried out by the terminase large subunit during a viral replication cycle. Firstly, it acts as an ATP-powered molecular motor to help viral DNA move into empty capsids. Secondly, it also serves as an endonuclease, cleaving the viral DNA to start and stop packing activity (Bleriot et al., 2020). The phylogenetic analysis of selected prophages with other closely related prophages provided important insights into the diversity and relatedness of phages. The Klebsiella prophages were found to be present with other known Klebsiella prophages showing close relatedness, whereas the prophages from Acinetobacter baumannii genomes were found to be monophyletic. In this study, the highest similar sequences for Acinetobacter baumannii ranged from 99.91 to 75.38%, indicating a relatively high degree of diversity among the phages. For Klebsiella pneumoniae, a total of 25 of the most similar phages were selected, with similarities ranging from 99.99 to 78.95%: indicative of a relatively high diversity within the species.\n\nRecently computational programs and tools have revealed unprecedented insights for the detection, functional annotation, and similarity analyses of potential prophages integrated within bacterial genomes (Breijyeh et al., 2020). The phages can be isolated and propagated relatively quickly and can be tailored to target specific strains or combinations of strains. The identified phages are highly specific in their action, which allows for targeted and personalized treatment. This reduces the risk of disrupting the action of beneficial bacteria within the body, unlike traditional antibiotics which can lead to collateral damage to the microbiome (Mu et al., 2021).\n\n\n5. Conclusion\n\nA phage cocktail against MDR Acinetobacter baumannii and Klebsiella pneumoniae was predicted computationally, which may prove useful to combat these bacterial strains that are resistant to a variety of drug treatments. Through extensive sequence similarity analyses, it was discovered that this phage cocktail might possess an ability to target other carbapenemase-producing Klebsiella pneumoniae strains as well, in addition to the initially selected MDR bacteria. As an alternative to conventional antimicrobial treatment, this highly specific phage cocktail could be developed in vitro and employed as a therapeutic agent for tackling certain MDR bacterial infections.\n\n\nAuthor contributions\n\nConceptualization: RN; Data Curation: AH, MAA and ZH; Formal Analysis: AH and MAA; Project Administration: UM; Supervision: RN and MI; Validation: AH, MAA, MS, AR, and WGC; Visualization: RN and WGC; Writing – Original Draft Preparation: AH, MAA and AA; Writing – Review & Editing: HAR and WGC.",
"appendix": "Data availability\n\nFigshare. Underlying data for ‘Computational prediction of a phage cocktail active against multidrug-resistant bacteria’. https://doi.org/10.6084/m9.figshare.27079600.v2 (Nawaz, 2024).\n\nThis project contains the following extended data:\n\n• BLASTp_analysis.xlsx\n\n• ORFs.xlsx\n\n• Promoter_sequences.xlsx\n\n• Terminators_sequences.xlsx\n\nData is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nAccession numbers:\n\nNCBI GenBank: Acinetobacter baumannii AB0057, complete sequence; Accession number: NC_011586.2; https://www.ncbi.nlm.nih.gov/nuccore/NC_011586 (Adams et al., 2008).\n\nNCBI GenBank: Klebsiella pneumoniae subsp. pneumoniae HS11286 chromosome, complete genome; Accession number NC_016845.1; https://www.ncbi.nlm.nih.gov/nuccore/NC_016845.1 (Liu et al., 2012).\n\nNCBI GenBank: Pseudomonas aeruginosa UCBPP-PA14, complete sequence; Accession number: NC_008463.1; https://www.ncbi.nlm.nih.gov/nuccore/NC_008463.1 (Lee et al., 2006).\n\n\nAcknowledgements\n\nWe would like to thank Dr. Samyyia Abrar for her assistance during the study and the Library of Superior University, Lahore, especially Dr. Furkan Yousaf, the chief librarian, for providing assistance and resources.\n\n\nReferences\n\nAbdulateef SA, Owaif HAA, Hussein MH: Importance of virulence factors in bacterial pathogenicity: a review. 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}
|
[
{
"id": "336822",
"date": "13 Dec 2024",
"name": "Laura Bonofiglio",
"expertise": [
"Reviewer Expertise Microbiology",
"bacteriophages",
"Streptococcus"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript presents a computational pipeline for designing a phage cocktail targeting multidrug-resistant (MDR) bacterial pathogens, including Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. By analyzing prophage sequences from bacterial genomes, the authors aim to identify and select potential phages for therapeutic applications. The pipeline integrates various bioinformatics tools for prophage detection, annotation of open reading frames (ORFs), identification of functional elements (e.g., promoters, terminators), and similarity analysis to previously characterized lytic phages. The study concludes with a proposed five-phage cocktail that could combat MDR pathogens.\nWhile the manuscript is well-structured and focuses on clinically relevant MDR pathogens, there are areas where clarity and depth are lacking, particularly regarding host range predictions, receptor-binding protein (RBP) analyses, and experimental validation. The speculative nature of the claims about the cocktail’s efficacy undermines confidence in its potential utility without additional experimental testing (e.g., in vitro or in vivo studies).\nSpecific Feedback Background The authors state that “this study integrated a computational pipeline to design a phage cocktail against A. baumannii AB0057, K. pneumoniae subsp. pneumoniae HS11286, and P. aeruginosa UCBPP-PA14.” However, given the lack of conclusive results for P. aeruginosa, it should not be mentioned in the background.\nThe manuscript does not clearly explain how the detection of ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and promoter sequences provides insights into the regulatory mechanisms of prophages and their interactions with host bacteria. Supporting references are needed to substantiate these claims.\nTables and Figures Tables 1 and 2 should be unified to better correlate the results of prophage prediction and identification. Similarly, Tables 3, 4, and 5 could be merged to simplify result interpretation. Figures 3 and 4 should clearly label the prophage genomes being compared. Table 6 and section 3.10: The title “Selection of viable prophages” should specify “possible viables,” as the predictions are based on in silico analyses. Table 7: It is unclear why sequence similarity between two A. baumannii prophages and known phages is mentioned when coverage is low. The authors should clarify whether the prophages identified have previously been used in phage therapy (e.g., Jeon et al., 2012; Bagińska et al., 2023; Lavigne et al., 2004).\nResults The selection of phages in Figures 3 and 4 is not well-explained in relation to Table 7. The selection criteria should be clarified. Moreover, beyond comparing similar phages, it would be helpful to compare the five selected ones using tools like EasyFig, highlighting what these comparisons reveal about their lytic potential.\nIn section 3.11, the results should begin by explicitly listing the five selected prophages. This information is currently unclear. Section 3.12 should be integrated into 3.11, as per the methodology, since the BLASTn analysis precedes comparative genomic analysis.\nDiscussion The authors propose a five-phage cocktail but do not explicitly state that the selected phages are part of the same cocktail. Furthermore, it is unclear whether the cocktail targets different species or strains of the same species.\nThe potential efficacy of the cocktail is questionable due to the lack of studies on phage-bacteria interactions, such as receptor-binding analysis. While some similarity to lytic phages is noted, the specific modules where these similarities occur are not detailed, except for the large terminase subunit (TerL). This relationship should be supported with references linking TerL similarity to host range.\nFor phages with antibacterial activity (e.g., Acinetobacter phage 5W, Klebsiella phage Mulock, Klebsiella phage KPP5665-2, and Bacteriophage YMC/09/02/B1251), the low coverage in Table 7 raises concerns. The authors should clarify whether the shared sequences are located in regions associated with lytic activity. A similar issue arises with Pseudomonas, where the rationale for excluding this genus from the phage selection process is not adequately addressed.\nThe similarity between the A. baumannii prophage (2759376-2809756) and Acinetobacter phage YC#06 (ON391949.1) is mentioned in the discussion but not included in Table 7. If coverage is high, this phage should be considered as a candidate.\nSeveral sentences in the discussion are more appropriate for the results section and should be removed, such as: “Prokka annotation of these prophages.” “A dot plot of selected phages was generated, which enabled us to reject K. pneumoniae prophage (4049881-4085225), which shared high sequence similarity with the K. pneumoniae prophage (1778306-1808606).”\nRecommendations Specify the phage modules with shared similarity for future inclusion in the cocktail. Suggest conducting in silico searches for bacteria-phage interactions to evaluate the spectrum of action. Justify the relevance of the large terminase subunit in assessing lytic potential with supporting literature. By addressing these issues, the authors can improve the clarity, applicability, and scientific impact of their work.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
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https://f1000research.com/articles/13-1292
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https://f1000research.com/articles/12-1577/v1
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11 Dec 23
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{
"type": "Study Protocol",
"title": "Evaluation of comparative efficacy of Celastrus paniculatus (Jyotishmati) capsule versus sertraline capsule in the management of Chittodvega (generalized anxiety disorder): protocol for a randomized controlled trial",
"authors": [
"Reeya Gamne",
"Sadhana Misar",
"Mayank Rai",
"Sadhana Misar",
"Mayank Rai"
],
"abstract": "Background Generalized anxiety disorder (GAD) (Chittodvega) is one among many types of mental disorders explained in Ayurveda. It can be defined as a Chitta (mind) + Udvega (anxiety)= Chittodvega- Anxious status of a mind. Celastrus paniculatus is one of the most important medicinal plants of the Celatraceae family commonly known as Jyotishmati. It stimulates and improves the digestive fire and metabolism at a cellular level (Jatharagni and Majja dhatwagni). It can be correlated to GAD. GAD is characterized by feelings of threat, restlessness, irritability, sleep disturbance, and tension, and symptoms such as palpitations, dry mouth, and sweating. It affects women more frequently than men and prevalence rates are high in midlife (prevalence in females over age 35: 10%) and older subjects. In modern medicine the first-line psychological and pharmaceutical treatments are selective serotonin reuptake inhibitors (SSRIs) like sertraline (SNRIs).\n\nAim and objectives To evaluate the comparative efficacy of Jyotishmati versus sertraline in the management of Chittodvega.\n\nMethods In this randomized clinical equivalence trial a total of 70 patients will be enrolled and divided into two equal groups. Patients between 20–50 years age of either gender having symptoms of Chittodvega and a Hamilton anxiety rating (HAM-A) scale score less than 24 (i.e., mild to moderate) will be selected for the study. In Group A, sertraline capsules 25 mg for first 7 days and then dose increased to 50 mg at bedtime for next 53 days and in Group B Jyotishmati Capsules 500 mg will be given twice a day after food with water for 60 days.\n\nResult and observation The patients will be assessed on the HAM-A scale, serum cortisol and WHO Quality of Life on day 0, 30, 60 and 90 and data collected will be analysed by using statistical tests.\n\nTrial registration CTRI No. REF/2023/07/069880 Date – 15/09/2023",
"keywords": [
"Chittodvega",
"Celastrus paniculatus",
"GAD",
"HAM-A Scale",
"Jyotishmati",
"Medhya",
"Sertralin"
],
"content": "Introduction\n\nAyurveda, due to its psychosomatic approach considers the mind as an integral part of life. It advocates the integration between the mind, body and soul with holistic approach. In our bodies, there are two different types of mind qualities (Manas doshas like Satva, Rajas, and Tamas) and bodily humours like (Vata, Pitta, and Kapha). Because bodily humours and mind qualities frequently interact with one another,1 Ayurveda accepts the idea of psychosomatic disorder. Of the three humours, Vata (Particularly Prana, Vyana, and Udana Vata) is primarily in charge of controlling and stimulating mental activity as well as generating enthusiasm. Sadhaka, a subtype of Pitta, has a direct connection to how the mind works. It is in charge of intelligence, memory, and cognition, as well as self-worth and enthusiasm.2 The qualities of Kapha (Tarpaka and Bodhaka, types of Kapha) include endurance, strength, knowledge, learning, wisdom, thinking, understanding, comprehensiveness, comprehension ability, equilibrium, enthusiasm etc.3 Generalized anxiety disorder (GAD) (Chittodvega) is referred to as the “anxious status of a mind” and is described as a Chitta (mind) + Udvega (anxiety).4 It is referred to as Raja-tama vikara in Charaka vimana 6 (Rogaanik vimaana adhyaya).5\n\nThe vitiation of mind qualities like Raja and Tama leads to the development of Chittodvega. Raja is aggravated by indulgence in causative factors, which also aggravates another mind quality, i.e., Tama as well as Vata, and Pitta. In Ayurveda Chittodvega (anxiety disorders) is described as one of the causes of psychosis (Unmada) rather than as a separate disease.6 One of the minor psychiatric diseases is chittodvega; there is no disorientation and the patient can carry out everyday activities without much trouble (i.e neurosis),7 whereas psychosis (Unmada) is a major psychological disorder (impairment of orientation, i.e. psychosis), and neurosis may leads to psychosis, so can be considered as prodromal of psychosis (Unmada).8\n\nThe symptoms of Chittodvega are similar to those of GAD, which are muscle tension, poor concentration, autonomic arousal, feeling “on edge” or restless, and insomnia. GAD manifests as persistent, excessive, and/or exaggerated worry. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) includes the following diagnostic criteria: anxiety and worry that has lasted at least six months.9 Controlling the worry is difficult. For at least 6 months, the anxiety is connected with three or more of the following symptoms: 1. Restlessness, tenseness, or apprehension. 2. Being easily exhausted. 3. Difficulty concentrating or going blank, as well as impatience. 4. Muscle tenseness. 5. Sleep deprivation. Irritability: anxiety causes severe distress or impairment in social and work settings.10 There is no physiologic reason for the worry.11\n\nMany disorders are more common today, and one of them is mental illness, which stands as India’s third largest health burden according to a World Health Organization (WHO) report.12 WHO estimates that 264 million people globally, or 3.6%, suffer from an anxiety illness. Additionally, anxiety affects 4.6% of females and 2.6% of males worldwide.13 The following primary categories of anxiety disorders are included in the DSM-5, according to the American Psychiatric Association: acute stress disorder, post-traumatic stress disorder, obsessive compulsive disorder (OCD), GAD, agoraphobia without panic, social phobia (social anxiety disorder), specific phobia, and anxiety disorder not otherwise mentioned.14\n\nIn modern medicine, GAD management consists of psychotherapy, like cognitive behavioral therapy (CBT) and pharmacological approaches such as cannabis, citalopram, escitalopram, sertraline, duloxetine, and venlafaxine.15 The first-line psychological and pharmaceutical treatments are CBT and selective serotonin reuptake inhibitors (SSRIs) like sertraline; alternative possibilities include selective norepinephrine reuptake inhibitors (SNRIs). Compared to other anxiolytics, SSRIs deal with depression, which is frequently co-occurring with anxiety and has less adverse effects.16 The World Federation of Societies of Biological Psychiatry recommends SSRIs, and SNRIs as first-line therapies for GAD. However the medicine should treat the condition without any adverse effects on the body. So, there is a need to search for better treatment with less complications.\n\nOne of the most significant medicinal plants in the Celatraceae family is Celastrus paniculatus, also known as Jyotishmati. It is a deciduous, woody forest climber that grows primarily in mountainous terrain. Jyotishmati is a combination of the words “enlightens” (Jyoti) and “brain functions” (mati), which means “enlightens the psychomotor function.” The seed oil (Jyotishmati taila) is well renowned for its intellect-promoting (medhya) properties. As a brain tonic, it is used to boost intelligence and improve memory.17 With its pungent and bitter taste and hot potency, Celastrus paniculatus (Jyotishmati) has an effect on three bodily humours of the body. It strengthens the ability of grasping and remembering (i.e Grahana and Smarana) and supports Sadhak Pitta (a subtype of pitta). Both digestion and cellular metabolism (Jatharagni and Majja dhatwagni) are stimulated and improved by its attributes.18 By clearing and opening the micro channel, it enhances circulation and offers appropriate nutrition.19,20\n\nIn Bhavaprakash Nighantu and Raj Nighantu it is mentioned as intellect promoting (Medhya) drug.21\n\n\nNeed for the study\n\nOne type of anxiety illness, known as generalized anxiety disorder (GAD), is marked by excessive worry and anxiety that the individual with it has trouble controlling. GAD leads to functional disability and a markedly reduced quality of life for the patient.22 This constituted 25–30% of psychiatric outpatients.23 International Statistical Classification of Diseases and Related Health Problems ICD 10 enlists anxiety as one of the symptoms. Anxiety has a significant financial impact on the healthcare system that cannot be overlooked. Its prevalence is about 2–4%, along with psychological arousal, muscle tension, sleep problems, and restlessness.24 Many people live with GAD, which makes it difficult for them to engage in relationships, employment, and other parts of life. Due to the problems of living in a materialistic, competitive society as well as the modern way of life, these types of symptoms and diseases are becoming more and more prevalent day by day.25\n\nTo reduce the impact of these ongoing health hazards, treatment regimens are always being sought for the management of anxiety and the reduction of stress. Substitutes to SSRIs, benzodiazepines, and other prescribed medication are highly sought after in an effort to reduce exposure to hazardous effects related to these drugs.26\n\nThe intellect promoting (Medhya) medicines described in the Ayurvedic texts have a powerful effect on the mind, have the ability to lower anxiety, and support mental wellness. It is also mentioned in the classics that the one who uses rejuvenating (medhya rasayana) drugs would attain longevity, memory, intellect, youth, luster, skin tone and voice, excellent functioning of the body and sense organs.\n\nPresently there is a need for safer and effective drugs for GAD (Chittodvega) and less research have been done in this regard in recent years. Celastrus paniculatus is one such herb mentioned having intellect promoting (Medhya) property.27\n\nAs a result, this study aims to assess the effectiveness of Celastrus paniculatus (Jyotishmati) capsules in the treatment of Chittodvega.\n\nAim: Evaluation of comparative efficacy of Celastrus paniculatus (Jyotishmati) capsules versus sertraline capsules in the management of Chittodvega (generalized anxiety disorder).\n\nPrimary\n\n• To evaluate the efficacy of Jyotishmati capsules on the Hamilton anxiety rating-scale (HAM-A) and serum cortisol level.\n\n• To evaluate the efficacy of sertraline capsules on the HAM-A Scale and serum cortisol level.\n\n• To compare the efficacy of both on the HAM-A Scale and serum cortisol level.\n\nSecondary\n\n• To evaluate the efficacy of Jyotishmati capsules on quality of life.\n\n• To evaluate the efficacy of sertraline capsules on quality of life.\n\n• To compare the efficacy of both on quality of life.\n\n\nMethods\n\nThe study will start after clearance from the institutional ethics committee of Mahatma Gandhi Ayurved College Hospital and Research Centre, Salod (H), Wardha. And after CTRI registration (Ref. No. REF/2023/07/069880) Date – 15/09/2023.\n\nThe committee will decide on the endpoint and oversee the trial as it progresses. The researcher will assess any adverse event and will report these to the ethics committee. The committee will decide on the endpoint and oversee the trial as it progresses.\n\nBefore conducting the trial, written informed consent will be taken from the patient in the local language while explaining every aspect of the study. The researcher will take consent from trial participants.\n\nThe personal information of the participants will be collected and kept confidential before, during, and after the trial. Physical data will be stored in a protected storage facility with only access to the researcher. Computerized data will be held in a password-protected hard drive with only access to the researcher.\n\nThe patients will be selected from Kayachikitsa Out-patient department and In-patient department 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 70 patients will be recruited for the study. They will randomly be divided into two groups; Group A – sertraline capsules, and Group B – Jyotishmati capsules. All the baseline parameters will be recorded at the start of the study. The patients will undergo treatment for 60 days for both groups. All the parameters will be recorded at the 0th, 30th, 60th, 90th day of the study duration.\n\nInclusion criteria\n\n• Patients willing to take part in a research study and ready to give written informed consent.\n\n• Patients will be selected according to DSM-V,28 ICD-1029 criteria for anxiety disorders.\n\n• A score of less than 24 on HAM-A scale.\n\n• Age group of 20 to 50 years of either sex.\n\n• Free of psychiatric conditions other than anxiety.\n\nExclusion criteria\n\n• Current primary diagnosis of a comorbid disorder deemed to require treatment prior to GAD, such as major depressive disorder, panic disorder, social phobia, obsessive compulsive disorder, post-traumatic stress disorder, or drug dependency.\n\n• Currently undertaking CBT with a psychologist.\n\n• GAD (Chittodvega) due to drug abuse, a medication or due to general medical state like hyperthyroidism.\n\n• Alcoholic, and self-harm or suicide risk.\n\n• Diagnosed with psychosis, schizophrenia, or bipolar illness currently or in the past.\n\n• Treatment with sertraline for two or more weeks within the previous three months.\n\n• Pregnant and lactating mothers.\n\n\n\n• Group A – sertraline capsules 25 mg at bedtime for 1 week, then increased to 50 mg with water for 60 days.\n\n• Group B – Jyotishmati capsules containing processed seed powder of Jyotishmati, 500 mg twice a day with water for 60 days.\n\nPreparation\n\nJyotishmati (Celastrus paniculatus) seed will be pulverized into powdered form which then will be sieved and three bhavanas (trituration) of Jyotishmati phanta will be given to it according to Churnakriya method mentioned in Sharangadhara Samhita in Dattatreya Ayurved Rasashala, Salod (H), Wardha.30 The processed powder will be filled into capsules.\n\nIntervention modification\n\nAny adverse effect during the treatment will be noted and will be informed to the ethical committee. The patients will be taken care of for the adverse effect. If participants want to drop out, this will be mentioned with the reason for discontinuing the treatment.\n\n\n\n• Primary – Reduction in Hamilton A score and serum cortisol levels,\n\n• Secondary – Improvement in quality of life.\n\nPatients will be treated for 60 days and assessment will be done up to 90 days as mentioned in Figure 1.\n\n\n\nPrimary Variable = Hamilton anxiety rating scale (Anxiety Assesment)\n\nBefore the treatment (sertraline) Hamilton Anxiety Rating Scale (mean ± sd) = 19.38 ± 4.318, (As per reference article).31\n\nAfter the treatment (sertraline) Hamilton Anxiety Rating Scale at 28 day (mean ± sd) = 15.70 ± 4.550,\n\nMean difference (δ) = 3.68\n\nPooled Std. Deviation = (4.318+ 4.550)/2 = 4.434\n\nSample size N = 31\n\nConsidering 10 % drop out = 3\n\nTotal sample size required = 31+3 = 34 per group.\n\nFor protocol purposes and according to the calculated sample size for each group is = 34\n\nAs per sample size calculation, total 34 patients will be recruited which include 31 patients and 3 drop outs. Data collected will be analyzed by using appropriate statistical methods. The patients of Chittodvega 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\nA total of 70 patients will be recruited for the study.\n\nThe intervention period will be from 0 to 60 days and follow up on the 0th, 30th, 60th and 90th day.\n\nThis protocol follows the SPIRIT guidelines.23\n\nPatients between 20–50 years of age of both gender having symptoms of Chittodvega and a HAM-A scale score of less than 24, i.e., mild to moderate cases, will be selected for the study.\n\nInterventional study.\n\nRandomized active controlled double blind equivalence trial.\n\nInvestigation – Serum cortisol level.\n\nDiagnostic criteria – DSM-V Diagnostic Criteria for Generalized Anxiety Disorder.32\n\n\n\n1. Hamilton Anxiety Scale – HAM-A assessment will be done on 0, 30, 60 and 90 days by asking the validated questionnaire attached in annexure.33\n\n2. Serum cortisol level – will be assessed before and after treatment in our lab.\n\n3. WHO Quality of life – assessment will be done on 0, 30, 60 and 90 days by asking the validated questionnaire attached in annexure.34\n\nAllocation sequence generation – Computer-generated random numbers.\n\nAllocation implementation – The researcher or the first author will generate an allocation sequence, enrol participants, and assign participants to intervention.\n\nRandomization will be done by computer-generated random allocation software by SPSS 7.0 to avoid bias in the study.\n\nA third person will do coding to allocate subjects in sequentially numbered, opaque, sealed envelopes in groups A or B (SNOSE Scheme) to avoid bias in the study.\n\nBlinding – Randomized active controlled double blind equivalence trial, i.e., trial participants and care providers will be blinded in the study.\n\nData will be assessed according to HAM-A Scale, WHO Quality of life, on 0th, 30th, 60th & 90th day and serum cortisol at baseline and after completion of treatment. See Table 1.\n\nThe raw material for the drug will be purchased from an authentic shop from Nagpur (Wagh brothers) and will be identified by the department of Dravyaguna and Rasashastra of M.G.A.C.H. and RC, Salod, Wardha.\n\nAfter the study, the data will be analyzed according to a suitable statistical test.\n\nThe collected data will be entered in the software SPSS version 22. Man-Whitney and Wilcoxon tests will be used if the distribution of data was not normal. A chi squared test will be used to compare the qualitative variables. Independent t-test will be used to compare the mean of the two groups in the normal distribution of data, and for comparison before and after data, the paired t-test will be used.\n\nDrug preparation is in process.\n\n\nDiscussion\n\nChitta (mind) + Udvega (anxiety) = Chittodvega, or anxious mental state. However, Chittodvega is a more appropriate expression for describing the entire anxious illness.35 As a result, the term Chittodvega is compared to GAD in this study. GAD patients exhibit chronic, excessive, and/or unreasonable worry that is accompanied by muscle tension, reduced focus, autonomic arousal, a feeling of being on edge or restless, and insomnia for at least six months. This disease causes the patient to have unfocused worry and anxiety that is not related to recent traumatic experiences, but it may be worsened by specific circumstances.36 GAD is a common mental condition in the general society as a whole with a prevalence of about 5%. Women are twice as likely as men to have this condition.37 Medication such as selective serotonin reuptake or serotonin-norepinephrine reuptake inhibitors are the first-line treatments38 but long-term use can have negative side effects such nausea, trouble sleeping, changes in appetite, dry mouth, headaches, and sexual dysfunction.39 In contrast, Ayurveda states that mental disorders (manas rogas) is where mind promoting (Medhya) medicines are used. Jyotishmati (Celastrus paniculatus) is a thorny climbing polygamodioecious shrub that may climb up to 10 m with the help of a nearby tree. It is found virtually across India, rising to an elevation of 1800 m in the subtropical Himalayas.40 The seed oil and fruit are often used for their tranquillizing, sedative, wound-healing, and other properties. The Ayurvedic application is primarily for its Medhya (brain tonic) activity. It can be used as a brain tonic to enhance intelligence and memory. Its Deepana (stimulating digestion) property help in improving deranged digestive fire (Agni) and thereby balancing bodily as well as mental humours (Sharir and Manas dosha)41 Jyotishmati is a renowned medicinal herb recognised for its brain-boosting properties that has been used for generations in Ayurvedic medicine to sharpen memory and improve concentration and cognitive function.42\n\nData monitoring: formal committee.\n\nThis protocol will be further published as a thesis to disseminate the study for GAD (Chittodvega). 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 by posters, papers and publications.",
"appendix": "Data availability\n\nZenodo: SPIRIT checklist for ‘Evaluation of comparative efficacy of Celastrus paniculatus (Jyotishmati) capsule versus sertraline capsule in the management Of Chittodvega (generalized anxiety disorder) – protocol for a randomized controlled trial’. https://doi.org/10.5281/zenodo.8125916. 43\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 recognize the invaluable assistance provided by the scholars whose articles are mentioned and referenced in the manuscripts. 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.\n\n\nReferences\n\nShilpa S, Murthy CV: Understanding personality from Ayurvedic perspective for psychological assessment: A case. Ayu. 2011; 32(1): 12–19. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nLatendresse G, Elmore C, Deneris A: Selective serotonin reuptake inhibitors as first-line antidepressant therapy for perinatal depression. J. Midwifery Womens Health. 2017; 62(3): 317–328. PubMed Abstract | Publisher Full Text\n\nFerguson JM: SSRI antidepressant medications: adverse effects and tolerability. Prim. Care Companion J. Clin. Psychiatry. 2001; 3(1): 22–27. PubMed Abstract | Publisher Full Text\n\nDebnath M, Biswas M, Shukla VJ, et al.: Phytochemical and analytical evaluation of Jyotishmati (Celastrus paniculatus Willd.) leaf extracts. Ayu. 2014; 35(1): 54–57. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDhumal SR, Shete RV, Adak VS, et al.: A review on Celastrus paniculatus wild (Jyotishmati): It’s species, geographical sources, phytoconstituents, and therapeutic uses and pharmacological actions. IJHM. 2021; 9(4): 112–118.\n\nBhanumathy M, Harish MS, Shivaprasad HN, et al.: Nootropic activity of Celastrus paniculatus seed. Pharm. Biol. 2010; 48(3): 324–327. Publisher Full Text\n\nDr Gamne R : Evaluation Of comparative efficacy of Celastrus paniculatus (Jyotishmati) capsule versus Sertraline capsule in the management Of Chittodvega (Generalized Anxiety Disorder) - RCT (Version V1). Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "281408",
"date": "05 Jun 2024",
"name": "Dr Savitha H P",
"expertise": [
"Reviewer Expertise Clinical research",
"Survey study",
"Literary 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\n1. Evaluation of comparative efficacy of Jyotishmati ( Celastrus paniculatus ) capsule versus sertraline capsule in the management of Chittodvega (generalized anxiety disorder) - A Proposed protocol for a randomized controlled trial 2. Introduction and need for study - need to include explanation behind comparing with sertraline as control as there are many other SSRIs. 3. Introduction is very lengthy and it needs to be crisp and clear 4. Repetitions in inclusion and exclusion criteria 5. Justify about the dose of both control and study drugs 6. There is difference in the prescription of control drug in abstract and study plan which needs to be corrected 7. Inclusion of a modern psychiatrist in the study enhances the quality of proposal 7. Discussion has to be crisp\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Partly\n\nAre the datasets clearly presented in a useable and accessible format? Not applicable",
"responses": [
{
"c_id": "11718",
"date": "20 Jun 2024",
"name": "Reeya Gamne",
"role": "Author Response",
"response": "Thanks for the review."
}
]
},
{
"id": "286303",
"date": "06 Jun 2024",
"name": "Punam Khobarkar",
"expertise": [
"Reviewer Expertise ayurveda cardiology",
"diabetes",
"insomnia",
"herbsl medicine",
"ayurveda"
],
"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.Title: It is precise and informative, giving a clear indication of the research topic. 2.Abstract: The abstract succinctly summarizes the background, objectives, methodology, and anticipated outcomes. However, it could benefit from a more detailed description of the study design, including specific statistical methods and anticipated sample size, to better inform the reader about the study's robustness and scope. 3.Introduction The introduction provides a comprehensive overview of GAD, detailing its prevalence, symptoms, and the limitations of current pharmacological treatments, such as side effects and dependency issues. The rationale for investigating Celastrus paniculatus (Jyotishmati) is well-grounded, citing its historical use in Ayurvedic medicine and previous studies suggesting its anxiolytic properties. 4.Literature Review: The introduction could be strengthened by including a more exhaustive review of contemporary studies and meta-analyses on the efficacy of Jyotishmati and Sertraline, thereby situating the current research within the broader scientific context. 5.Aims and Objectives The study’s aims and objectives are clearly articulated. The primary objective is to compare the efficacy of Jyotishmati and Sertraline in reducing anxiety symptoms as measured by the Hamilton Anxiety Rating Scale (HAM-A). Secondary objectives include assessing changes in serum cortisol levels and evaluating quality of life improvements. 6.Methods a.Study Design: The study employs a randomized clinical equivalence trial design, which is appropriate for comparing the effectiveness of two interventions. However, further elaboration on the randomization process, blinding procedures (if any), and controls to mitigate bias would enhance the methodology's rigor. b.Participants: Inclusion and exclusion criteria are well-defined, ensuring a relevant study population. Yet, additional details on the demographic characteristics of the target population would be beneficial. c.Intervention: The interventions are described with adequate detail, specifying the dosage and duration of treatment for both Jyotishmati and Sertraline. However, the manuscript should provide more information on the standardization and quality control of the Jyotishmati capsules used. d.Outcome Measures: Primary and secondary outcome measures are appropriate and clearly defined. The choice of HAM-A for primary outcome and serum cortisol levels, along with quality of life assessments, as secondary outcomes are justified. Including information on the validity and reliability of these measures within the study context would be advantageous. e.Data Collection and Analysis: The data collection methods are thorough, but the statistical analysis section is underdeveloped. A more detailed plan, including sample size calculation, power analysis, handling of missing data, and specific statistical tests to be used, would enhance the study’s scientific rigor. f. Ethical Considerations The manuscript adequately addresses ethical considerations, mentioning informed consent, confidentiality, and the approval by an institutional ethics committee. This reflects adherence to ethical standards in clinical research. 7.Expected Outcomes: While the manuscript outlines expected outcomes, it should also discuss potential challenges and limitations in greater detail, such as sample size constraints, adherence issues, and potential biases. 8.Discussion: The discussion should provide a balanced view of the study's potential impact on clinical practice and future research. It should also elaborate on how the findings could influence the treatment paradigm for GAD, especially in contexts where traditional and alternative medicine practices intersect. 9.Strengths: Comprehensive background and rationale for the study. Clearly defined aims and objectives. Detailed description of interventions and outcome measures. Ethical considerations are well addressed. 10.Weaknesses: The abstract could be more detailed regarding the study design and statistical methods. The methodology section lacks comprehensive details on randomization, blinding, and statistical analysis. The literature review in the introduction could be more exhaustive. The discussion does not sufficiently address potential limitations and the broader impact of the study findings. The manuscript presents a well-conceived study protocol to compare the efficacy of Jyotishmati and Sertraline in managing GAD. Addressing the noted weaknesses, particularly in the methodological and analytical details, will enhance the study's scientific validity and reliability. This research has the potential to provide significant insights into alternative treatments for GAD, contributing to the broader field of integrative medicine.\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? Partly",
"responses": [
{
"c_id": "11727",
"date": "20 Jun 2024",
"name": "Reeya Gamne",
"role": "Author Response",
"response": "THANKS FOR THE REVIEW."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1577
|
https://f1000research.com/articles/13-1288/v1
|
28 Oct 24
|
{
"type": "Research Article",
"title": "Re-conceptualising the Theory of Justice and the Needs of Victims of Sexual Violence in Nigeria: an Appraisal of a Victim Centered Approach",
"authors": [
"Cynthia Chukwufumnanya Izu",
"Sesan Fabamise",
"Oriola Oyewole",
"Sesan Fabamise",
"Oriola Oyewole"
],
"abstract": "Abstract\nBackground In the 21st century, the recognition of the rights and needs of victims of sexual violence has emerged as a fundamental discourse within international, regional, and local policy agendas. This has been influenced by the lasting psychological, emotional, and physical effects of sexual violence on the victims. These commentaries and agitation have spurred the need for alternative ways in which the Nigerian criminal justice system can be strengthened by incorporating criminal justice mechanisms and interventions that would enhance the needs and interests of victims in accessing justice despite its adversarial system of justice.\n\nMethods This study aims to appraise the different mechanisms of justice, needs, and interests of victims of sexual violence through a theoretical lens and drawing lessons from South Africa and Australia. To achieve this work, a doctrinal research methodology that utilized existing literature and secondary sources such as textbooks and online websites was adopted.\n\nResults The study found that there is a need for accountability for the protection of victims, implementation of legislation, and scaling up of resources for effective support services. In addition, the absence of resources, effective monitoring and compliance institutions, monitoring reports, specialized courts, and special regulations hampers the implementation of a victim-centered approach. Among others, the study recommends an all-inclusive criminal justice mechanism that would further incorporate a victim-centered approach towards advancing the rights and quality of justice for victims of Sexual Violence and the need for a victim impact statement to our criminal justice system for cases of sexual violence.\n\nConclusion The study concludes that there is a need to make provisions for more effective alternative responses to incorporate the justice interests and needs of victims of sexual violence.",
"keywords": [
"ustice",
"Rights",
"Victims",
"Sexual Violence",
"Victim Centered Approach and Nigeria."
],
"content": "1. Introduction\n\nGlobally, Sexual Violence (SV) is a special offence that is complex in nature and affects women, men, children, and society. Research shows that females living in Nigeria could experience at least one form of Sexual Violence (SV) before turning 30years old (De Veauuse Brown et al., 2022). Governments and non-governmental organizations, in an attempt to curb the menace and the ugly trend, have supported interventions with the passage of the Administration of the Criminal Justice Act (ACJA) (ACJA, 2015). Violence against Persons and Prohibition Act (VAPPA) (VAPPA, 2015), establishment of sexual assault referral centers, and sexual offenders registers. The ACJA provides for cost, compensation, and restitution to be made to the victims of crime, which is one of the alternative justice mechanisms that employs a victim-centered approach. However, these provisions are unrealistic for victims, particularly victims of Sexual Violence, as they lack accountability, effective monitoring institutions, and implementation. In addition, despite the laudable efforts of VAPPA and its introduction to victims’ rights, there is largely an increasing gap and demand for services (medical, psychological, counselling) to victims of sexual violence, accountability, quick dispensation, and access to justice and victims’ participation during the trial. The study argues that any effective criminal justice system must allow for the implementation of laws, regard the interests of victims and offenders, and hold perpetrators accountable for their acts.\n\nAdditionally, the study posits that for the criminal justice system to be effective, victims must be engaged in the system. To make criminal justice responses fairer and more just for victims of sexual violence, the first step must be to listen to victim/survivors. The potential of the criminal justice system as well as other systems’ institutional and organizational responses to provide a sense of justice to victim/survivors is discussed in the subsequent chapters based on victims’ narratives. Therefore, there is a need for a justice system mechanism that enhances victims’ dignity, a safe, supportive, and non-judgemental environment, appropriate information, victims’ right to privacy and confidentiality, and accountability of defendants (UN Women, 2019). Another basic aim stated in the UN Declaration (UN Declaration, 1985) for victims is that all victims should be able to exercise their rights within the justice system as well as receive support throughout the process, and that the justice system should not hinder the victims’ search for justice. Therefore, this study seeks to identify the rights and needs of victims of sexual violence from a theoretical perspective and to draw lessons from selected jurisdictions.\n\nTo further advance this study, concepts such as justice, victims’ rights, feminist theory, restorative theory, therapeutic jurisprudential theory, and all-inclusive theory will be examined. In addition, to achieve this, a doctrinal research methodology was adopted.\n\nThe concept of the term ‘Justice’ lacks a generally acceptable definition (Thursday and Duson, 2021). The meaning of justice is dynamic, and a range of justice paradigms have emerged in the recent administration of criminal justice and practice worldwide (Iliadis, 2020a). Justice has always been defined from different perspectives. Over the years, justice has been perceived more as a punishment, particularly through the practice of retributive justice within the Nigerian Criminal Justice System. However, with the grappling need to shift the focus away from offenders to victims to meet their interest and justice needs, the world is agitating for pathways for criminal justice reforms. The raging question the study tends to answer is whether justice for victims of sexual violence should be solely retributive given the adversarial nature of criminal justice in Nigeria. Black’s Law Dictionary (Garner, 2014) defines justice as follows:\n\nAn equal treatment being given to everyone; the act of being fair or reasonable; the manner in which individuals, cases, or their matters are adjudicated, especially the justice system where people are punished for crimes they commit; the even-handed application of justice.\n\nClark (Clark, 2010) asserts that the expectations of sexual violence victims’ justice are multi-layered and vary depending on a certain range of factors relating to the circumstances of the offence, the individual victim, and the victim’s relationship (if any exists) with the accused. Furthermore, according to Clark, victims seek different explanations and justice systems to assist them in regaining the power they once had and making amends for the harm they have suffered. This is a result of the varying demands and expectations of victims. Jordan (Jordan, 2008) argues that victims of sexual assault may not always receive justice from the traditional legal system. The rationale was based on the idea that victims may be reporting in order “to regain a sense of personal safety, and to have their experience validated,” rather than always expecting the criminal to be apprehended and found guilty (Clark, 2010). These conclusions are corroborated by Kelly (Kelly, 2020), which involved the interview of 100 rape victims in Washington, DC. Kelly discovered that although victims welcomed the idea of the offender/accused being found guilty, a conviction ultimately had little impact on their level of satisfaction with the legal system.\n\nAccording to Aristotle, the search for justice has not been accomplished (Durant, 1961). His definition acknowledges universal, distributive, and corrective justice. In Aristotle, Distributive Justice refers to the distribution of all resources and goods in equal measure. His corrective justice promoted the rectification of imbalances. As Cardozo, a one time justice of the Supreme Court of the United States said, ‘justice though due to the offender is also due to the victim’(State of Punjab & Bakshi, 2015).The concept of fairness must not be extended to the extent that it is reduced to a thin thread. In his view, there must be a balance between the rights of offenders and victims. If we remove justice from the criminal justice system, we are left with a system that rewards only the criminal (Durant, 1961). To ensure that justice is not removed from the criminal system and that a system was only the perpetrator’s benefit, the role of the victims has started to change dramatically in the criminal justice system of nations in the last few years by providing them with an important place in the criminal justice system and by affording victims a better chance of being compensated either through civil action or criminal compensation or indemnification (Cuomo, 1992).\n\nIn the case of Jago v. District Court of New South Wales, Brennan held that justice can be better served when victims’ interests are considered in proceedings (Jago & District Court of South Wales, 1989). According to the Australian Institute of Family Studies (AIFS) (Iliadis, 2020b) victims’ perceptions of justice ‘are formed with reference to the totality of the victims’ experiences within the process.’ This study examined the effects of victim-focused reforms on victims’ criminal justice experiences at a multi-jurisdictional level. The AIFS concluded in their research that the experience of the process defines justice, not the result of the process. For most (victim) participants, getting (justice) meant getting knowledge, affirmation, and respect. There has long been acceptance that the only way to perceive any kind of justice is to be convicted, but from recent research, this may not always be the case.\n\nDrawing from the above scholarly works, justice has no generally accepted definition, but one thing is recurrent in most definitions: equality and fairness. Therefore, this study considers justice as a process that responds to the needs and interests of victims at every stage until an outcome is reached, which puts the victim in a state of wholeness and acceptance. Invariably, whatsoever outcomes so far, the victims climax to a state of wholeness that itself is justice. In addition, the pursuit of retribution justice is neither the primary nor the only element that influences a victim’s degree of satisfaction within the criminal justice system. Therefore, a deeper comprehension of victims’ justice requirements is required to provide a more thorough and nuanced explanation of the variables influencing and forming the perceptions of justice held by victims of sexual violence. Some of these requirements are access to justice, the assessment of rights, and theories underpinning the study.\n\n\n\n\nThe United Nations Declaration of Basic Principles of Justice defines a victim as:\n\nArt. 1: Victim refers to an individual or a group of individuals who have been directly affected or having suffered a loss or damage in any form through an act or omission that is prohibited by the criminal law enforceable within the member states. Even those laws outlawing criminal abuse of power. Art. 2: The term victim also includes where appropriate the direct victim’s immediate family or dependents and person who have suffered harm in intervening, to assist victims on distress or to prevent victimization.\n\nBlack’s Law Dictionary defines victims as individuals affected by crime, torts, or any other form of wrong (Black’s Law Dictionary, 2004). In the words of Karibi (Karibi, 1990), a ‘victim’ of a crime is any person, dependent, or institution that has been harmed by an offender. Dignified treatment refers to the proposition that the victim should be treated with ‘compassion and respect for their dignity’ and secondly, that the victim should be endowed with ‘the right of access to justice and that justice be bestowed on the victim with haste for the wrongs that the victim has had to endure. However, the notion of compensation starts when restitution ends and looks forward to the possible, though remote, benevolence of States. If compensation is not available in full from the offender or from other sources, states should strive to ensure that financial compensation is provided to the victims, their families, and dependents, and to other applicable forums, including trust funds, where necessary. It should be noted that, as has been seen, the trial chamber of the ICC in the case of Prosecutor v. Thomas Lubanga Dyilo (Prosecutor & Lugbanga Dyilo, 2008) extended the definition of the victims under Rule 85 of the Victims Declaration to mean any person who had ‘suffered harm as a result of the commission of a crime within the jurisdiction of the Court,’ but this decision was overturned by the Appeals.\n\nThe UN, in its Security Council Resolution (Resolution 2468) that was passed in April 2019, admitted there are loopholes in the policies and laws that seek to address sexual violence, which requires a victim-centered approach (Ojo et al., 2021). Recently, the resident representative of the UNDP, Mr. Simon Ridley, recommended that all EU-UN interventions should align with victims’ modality, norms, and international standards (SGBV, 2017). Further, General Recommendation 35 of the CEDAW Committee also considered that all the measures for addressing GBV should be adopted with an approach that focuses on the victim/survivor, the women’s human rights approach, which embraces agency and autonomy for women and girls of all ages, and developing the capacity of girls from childhood to adolescence. Furthermore, it is crucial that the measures are developed and adopted with the involvement of women and their specific context with regard to women, discriminated based on multiple reasons.”\n\nRegardless of the affiliation of the accused perpetrator, the victim-centered approach places the rights and dignity of victims, including their well-being and safety, at the forefront of all efforts to prevent and respond to sexual exploitation, abuse, and harassment. From a victim’s perspective, justice may serve many other purposes, and being victim-centered recognizes that justice is multifaceted and subjective. For some victims, justice may mean punishment and conviction for others; it may be tied to dignity, truth, or the ability to tell one story in a safe space. Furthermore, in adopting a victim-centered approach, justice can be a vehicle for empowerment or a pathway towards simply feeling happier, healthier, and reconnecting to the community. It could also infer an ability to seek divorce and leave a violent spouse or acknowledgement the harm done to them.\n\nAccording to South African activists Dyantyi and Sidzumo (Decker, Wood & Kennedy, 2020), in addressing how the system strips victims of power, a victim-centered approach is used. It refers to the challenges they encounter in terms of these support systems, assists them in engaging with such systems in a way that does not re-entrench their disempowerment, and centers on their re-humanization throughout this process. In reality, the Nigerian Criminal Justice System has little regard for victims – even victims of sexual violence – who may be viewed as inconvenient to a smooth prosecution, yet often serve as a witness for the prosecution (Manty, 2001). This is because the NIS criminal justice system is more offender-focused than victim-focused. By being offender-centered, the system places more emphasis on guilt, punishment, and offender rights. The needs of the victim have never been considered, and the question has never been raised. After the prosecution of the criminal trial, the offender, if found guilty, is punished by one form of punishment or the other. This ends the pursuit of justice. A victim-centered approach is recognized as an international best practice in handling victims under the Criminal Justice System. It is a grand attempt to alter the criminal justice process so as to eliminate the principle of innocence until proven guilty, raise chances of conviction, and recast the process as a vital mental health intervention for self-identified survivors. As pointed out by Flynn, victim-centered approaches have been formulated to meet the special needs of vulnerable and threatened victims, including sexual violence victims (Iliadis & Flynn, 2018). Acknowledgement of the special needs of sexual violence survivors aligns with the general mission of adversarial systems that state that justice has been receiving more emphasis on equality, fairness, and respect for the rights of the victim and offender. In its implementation, victimology must employ a multi-sectoral response that encompasses medical treatment; psychosocial services such as mental health services; security services that include police; other law enforcement responses and protection measures; and judicial and legal services.\n\nIt is pertinent to note that the terms sexual violence, sexual assault, and rape will be used interchangeably in this research. According to Pedersen, Sexual violence is widespread worldwide (Pedersen, 2020). Sexual violence affects women, girls, men, and boys. Sexual Violence has been described as an act of violence that exposes a victim to the risk of physical harm, psychological harm, emotional harm, pregnancy, and STD. As highlighted by Peterson et al., sexual violence is a recognized public health concern, and the physical and mental health consequences of sexual violence, either in the short or long term, include increased risk of sexual and reproductive health complications, including suicide or contracting HIV (Peterson et al, 2017). For instance, in Ejieke Maduka v. Microsoft Nigeria Limited and three Ors (Ejieke & Microsoft, Nig. Ltd, 2012), the National Industrial Court of Nigeria recognizes that sexual harassment violates the provisions of Section 34 (1) (a) of the CFRN, Articles 2 and 5 of the African Charter asserting that the dignity of persons is a human right and that degrading treatments are prohibited (Ejembi et al., 2020). The WHO also noted that sexual violence has severe effects on physical and mental health as it leads to sexual and reproductive health issues with short- and long-term effects such as HIV/STIs, pain, illness, pregnancy, loneliness, and PTSD. The type of sexual violence includes rape, which can be caused by an acquaintance or a stranger, stalking, sexual harassment, forced trafficking, female genital mutilation (FGM), child sexual abuse, and forced marriages. For instance, it has been estimated that one in every five women across the globe will be raped or have attempted rape in her lifetime (UN, 2008).\n\nHere, theories that support the applicability of a victim-centered approach are analyzed. The theories will provide a jurisprudential analysis of why needs and rights are relevant in reconceptualizing justice for victims of sexual violence in Nigeria within the Criminal Justice System. Theories such as Feminist, Restorative, therapeutic jurisprudence, and all inclusive theory will be examined.\n\nIn recent decades, feminist activists and women’s movements have fought against patriarchal structures and systems that support violence against women and justify the legal system’s treatment of victims of sexual assault as a means of oppression, undermining women’s equality, freedom, and access to the justice system. The social, legal, and political contexts defining responses to victims of gendered violence have also been criticized by these movements. Under this theory, the researcher will look at feminist critiques of the criminal justice system’s response to sexual violence and their call for a more efficient justice system for victims of sexual violence. Since criminal justice is always found to be incapable of responding to cases of sexual violence, feminist scholars have recently shifted their focus to how justice can be sought outside the legal system (Daly, 2017). Feminist advocates and victims’ rights groups have also persisted in reforming the social, legal, and political contexts for responding to victims, especially those of sexual offences, which has led to remarkable changes in how victims are seen and treated in the criminal justice system as a result (Iliadis, 2020b). This has led to further enhancements in the social and service rights of victims associated with information, compensation, VISs, and security features, including video remotes and restrictions on questions about the experiences of complainants of sexual assault during trials. Feminist theories are quite diverse, and it is possible to identify some that are contradictory to each other. Nonetheless, the focus of most feminist interferences, including those that contradict each other, is to respond to the needs and justice issues of survivors of sexual assault. According to Zehr (Zehr, 2003) victims face various demands. Thus, they require opportunities to express their emotions. They must be compensated for the losses. Victims require justice: they require an ethical declaration of their innocence, identifying the guilty party, and emphasizing that this should not have occurred to them. These require responses to queries that bother them. Since perpetrators have taken their authority away, they require it to be restored.\n\nO’Connell (O’Cornell, 2015) opines that despite many changes in the role and level of recognition granted to victims of sexual assault, they continue to experience alienation and exclusion from the prosecution process. To advance the above, O’Connell concludes that victims’ rights remain a secondary consideration in the legal system and that there is a need for victims’ reform. Daly calls for new and more ‘innovative’ ways to address sexual violence issues. She proposes restorative justice wherein she agrees that victims of sexual violence need a justice mechanism that will offer them an ‘informal’ environment in which to discuss the impact of the crime upon them and redress the harm (Daly, 2011). Hudson (Hudson, 2002), is of the opinion that the Criminal Justice System has failed to eradicate the causes of Sexual Violence. Instead, its practice has served to maintain its prevalence. Consequently, while attempting to convince victims of its effectiveness, the overall Criminal Justice System has made little progress up to this point in time. Another area neglected by the Criminal Justice System is the need for victims of sexual violence. However, other authors have noted that this is likely because there is limited comprehension of what it means to achieve justice for victims and what the requirements of sexual violence victims are (Herman, 2005). Major Proponents of Restorative Justice exclude punishment as part of Restorative Justice because it does not seek to cause any form of pain/harm to an offender but rather aims to repair the harm done (Zernova, 2016). As a result, Restorative Justice has been described as a soft option or ‘cheap justice’ (Coker, 1999). If this is the case, it becomes impossible to believe that deterrence theory can stand for this idea. This raises the question whether Restorative Justice can contain the public’s wrath of Sexual Violence. Similarly, the broader category of the feminist school holds that reparative steps are inadequate in the endeavor to stigmatize the offence and deter wrongdoers. Specifically, feminists argue that extending the use of Restorative Justice to this area will reduce the gains made over the years with the aim of ensuring that Sexual Violence is addressed seriously (Naylor, 2010). By contrast, supporters of this practice focus on the shortcomings of the Criminal Justice System in addressing the multiple needs of victims of Sexual Violence. Opponents have predicted that the core principles of Restorative Justice, because the procedure is not mainly legal, will increase the number of reported Sexual Violence cases by victims where the offender is a relative. Furthermore, most feminist scholars such as Pali (Pali, 2017), Zinsstag and Keenan (Zinsstag and Keenan, 2017) affirm the assumption that there is no permissive reason to exclude restorative justice in sexual violence cases when certain standard precautions are taken, including culturally sensitive, trauma-informed, and evidence-based approaches (Sardina & Ackerman, 2022).\n\nThere have been discussions regarding the application of RJ in Sexual Violence over the last few decades. Some of the arguments that have been made include the following from the victim and the society. Some arguments lie in the possibility of encounters between an offender and victim (Umbreit, 1999). More importantly, feminists argue that the use of RJ in Sexual violence will reverse the gains made in the last few decades to address sexual violence (Naylor, 2010). On the other hand, proponents of this practice point to the shortcoming of the Criminal Justice system in addressing the multifaceted needs of victims of Sexual Violence, thereby supporting RJ. Generally, when one is faced with the concept of using RJ for Sexual Violence cases, what one would usually wonder is what can be rebuilt after a crime of Sexual Violence has been committed? In the usual construction language, ‘reconstruction’ implies that a victim can be brought back to his or her previous position. This question may not be asked in the case of property offences, since replacement of the item will put the victim back to the state he was before the commission of the offence. However, for cases of sexual violence, the question that follows is, is it possible to restore a victim of sexual violence? When asked, Daly (Daly & Curtis-Fawley, 2005) opines that people end up having a very narrow definition of the word ‘restorative’. She points out that RJ is more a label that refers to a range of activities than about ‘restoring.’ Critics counter argues that there are positive features of RJ that include the fact that the process is non-adversarial, and thus the reporting rate of offences of Sexual Violence, particularly by relatives, will rise.\n\nDespite the potential benefits of RJ for victims, it is also important to note that RJ may indeed recreate some of the problems identified with the Criminal Justice System. As Ptacek put it in her own no-nonsense manner, “restorative practices were not designed to address crimes of violence against women.” The main strain of this argument is that RJ replicates victimization. The author recognizes that restorative justice serves a significant purpose in various settings, such as juvenile crime, family law (if there is no violence involved), and probate issues. Those who support its use in other cases, however, object to adopting a restorative model for sexual violence because of its possible effects on victims.\n\nThe major proponents of the use of RJ for Sexual Violence affirm that the criminal trial process has been widely accepted for its ability to traumatize victims because of the existing rules that allow for a language of denial. This normally occurs when defense counsel is through the defense examination process. On the other hand, the restorative process (where appropriately implemented) should prevent victims’ revictimization as well as ensure that either the offender or the community does not adopt victim-blaming attitudes (Koss, Bachar & Hopkins, 2003). In the same regard, the process helps the victim recount her ordeal in a safe environment, with full support accorded to the victim (Edwards and Haslett, 2003). This cannot be said of the criminal justice process, whereby the voices of the victims are only considered when they are invited to testify. Finally, RJ can offer more options to different kinds of victims, some of whom do not wish to prosecute the offender, and it is also flexible in addressing the cultural and religious background of a victim. For instance, Delta State Law on Administration of Criminal Justice whereby the law provided for the use of digital/video conferencing for cross-examination of victims. The other powerful argument of antagonist scholars is whether Restorative Justice can act as a deterrent. This has been opposed to punishment because RJ does not use any form of harm/pain in an offender but aims to repair the harm. Hence, it has been described as a soft option or ‘cheap justice’ (Coker, 1999). If this is the case, he argues that it is unlikely that deterrence theory can be applied to this concept. Thus, questions arise as to whether RJ can capture social attitudes towards Sexual Violence. In response, advocates have posited that while the idea cannot guarantee the actualization of general prevention, it may be capable of producing individual prevention (Cunneen and Hoyle, 2010). Depending on the level of understanding of the victim and the degree to which the abuser visibly experiences the social condemnation of the members of his society, this kind of ‘shaming’ may marshal the society’s condemnation of this act (Braithwaite & Daly, 2013). It may therefore lead to individual deterrence. According to King (King et al., 2014), many offenders, especially those who have had an opportunity to meet victims during the program, stated that it was uncomfortable and even more difficult than ordinary retribution. Being given a direct responsibility to take personal blame for the injury to which they contributed can be much tougher than facing a judge and a nameless jury.\n\nGenerally, therapeutic justice is a framework that requires the court to use and promote healing for victims of crime and offenders (Imiera, 2018). The involvement of therapeutic justice in the criminal justice system emerged in the 1990s during David Wexler’s exploration of ways to harness therapeutic power within the criminal justice system (Wexler, 1990). Therapeutic Justice suggests that a legal process must be responsive to the impact of its consequences on parties involved in the criminal justice procedure (Wilson, 2021). It further advocates how the law can be therapeutically applied to reform the Criminal Justice System. In addition, therapeutic justice holds that something as simple as the approach used by a judicial officer to handle a case influences a person’s welfare. It targets the special demands of the people involved in particular circumstances of crime and challenges them to join a personal and confidential process in which they can think about what is required to rebuild their lives. Therapeutic justice seeks to determine the effect of substantive laws, legal rules, legal procedures, and the behavior of legal players, including judges, lawyers, court staff, and service providers, on the psychological and emotional well-being of justice system participants (Babb and Wexler, 2018). Therapeutic justice has appeared as a new criminal justice model (Daly and Marchetti, 2012); it is a reformist paradigm since it postulated that evidence from behavioral and social sciences should inform the development of advocates of therapeutic jurisprudence, affirming that extending recognition to the voices of crime victims improves their mental state and condition (Freckelton, 2008). The poor treatment and violation of crime victims in the criminal justice system only strengthens the weaknesses of the justice system, which marginalizes the suffering of crime victims and thus increases it (Imiera, 2018). Actually, actions taken against the offender help a lot in responding to the pain felt by crime victims and their families due to the crime. Instead, healing is a complex, continuous, and time-consuming process through which crime victims need to engage in proactive efforts to restore their well-being in the aftermath of a crime.\n\nIn addition, although Therapeutic Justice may advance a new way of administering justice, Van der Merwe opines that the onus and responsibility are on courts to impose balanced (Van der Merwe, 2007). Therapeutic justice is significant to today’s modern-day criminal justice adjudication system as it builds on collaborative and consensual processes, not only to determine the crime but also to assist in offender retreatment and rehabilitative programs that reduce recidivism (Iwuagwu, 2003).\n\nPradeep concludes that therapeutic justice is significant in that it releases support to crime victims and, in turn, helps provide relief from strong or repressed emotions (Pradeep, 2015).\n\nAn all-inclusive theory of justice will entail a system that allows victims to choose a process within the Criminal Justice System that will effectively address their needs and situations. The above theory is based on the notion that victims themselves are in the best position to determine the approach that is most appropriate to their circumstances. Here, victims are offered three choices, and the requirement that a victim choose between two options must be made by her and not by her attorney or judge, although the victim may be advised. The first option will be for victims who may wish to confront their abuse informally by opting for restorative justice. Through this channel, a victim can arrange a meeting with an accredited Restorative Justice organization to meet with him/her, the offender, and members of their respective communities in accordance with any of the models of Restorative Justice, which shall be discussed in chapter four of this thesis. For instance, this approach may be useful in the case of an adult victim or a victim of child sexual abuse because of the high rate of failure when prosecuting such a crime owing to the delay in the time in which the offence was committed. The second option concerns those who want to pursue justice through the Criminal Justice System. Criminal charges are initiated against an offender.\n\nThe third option is a combination of both retributive and restorative justice. This approach addresses victims who want to engage in restorative justice and those who want retributive justice. Issues regarding the question of deterrence will also be discussed if this approach is adopted because both individual and general deterrence can be affected. The use of both retributive justice and restorative justice shall give structure to the victim-centered approach in addition to addressing some of the safety concerns of victims. For example, an order of protection may be made against the offender and will only be lifted once parties are sitting for a restorative justice program. Likewise, the Criminal Justice system machineries of enforcement can also be utilized to enforce restorative agreements between parties.\n\nThis study examines a few practices in South Africa and Australia. These Countries were selected because of their common law similarity with the Nigerian Legal system and the practice of the adversarial system of justice. Some of the lessons learned are as follows.\n\n1.10.1 South Africa\n\nIn the case of S & Matyityi, Supreme Court of South Africa (Matyityi, 2011), it was noted that there is a need to change and adopt a more victim-centered approach in the criminal justice system. The Court’s decision shows that has a legitimate and important purpose; hence, the rationale of rape shield provisions and, more importantly, Rights in the Bill of Rights are not exclusively for accused persons (Prinsloo & Bramley Children’s Home, 2006). In a small measure, South Africa was able to introduce the following:\n\n1. Establishment of Victims’ Support Bill\n\nThe Department of Social Development has crafted the victim empowerment support service bill. This Bill mandates the state to provide and take financial responsibility to support victims and regulate the norms and standards of such services.\n\n2. Provision of Thuthzela Care Centres\n\nAt present, 55 Thuthuzela Care Centers (TCCs) and 60 Sexual Offences Courts are integrated in terms of how sexual offences are handled. Thuthuzela Care Centers are health facilities that offer appropriate treatment, counselling, and psychosocial support to survivors through non-governmental organizations, SAPS investigators, and prosecutors, known as case managers. The cases reported through TCCs have been associated with higher conviction rates 12 on the sources of funding, it will be observed that TCCs are mostly donor funded rather than state funded and a recent decision of a major donor about it has led to withdrawal of funds from 27 TCCs. According to the Members of the Campaign, this is likely to affect the psychosocial support and counselling services provided to the victims. Unfortunately, the South African government has not moved to fill this funding deficit, despite the effectiveness of this model. The TCC-model is a loading approach to rape care compliments designed for the purpose of comforting the victims of rape, making them feel dignified, and fighting for justice. The efficiency and effectiveness of cooperation with stakeholders underpin the working of TCCs.\n\n3. Provision of Rape Shields\n\nThe legislative goals of rape shield laws are targeted for a number of social reasons. One of these is to shield victims of sexual offence victims from being victimized under the legal process as the process can be demeaning, intimidating, and humiliating for the complainant (Jameelah, 2016). Rape shield laws also protect the right of the administration of justice by protecting the constitutional right of the complainant from humiliation and violation of her right to privacy to such an extent that she fails to testify effectively (Smythe, 2005). In another authority, Sv Mothopeng (Mothopeng, 1979), the court reaffirmed that there is a need to properly administer justice by ensuring that if a witness wanted to testify, he or she should not be able to be retaliated against. Decreasing secondary victimization is connected with enhancing the reporting of sexual offences. The Court in the case of S v Staggie (S & Staggie, 2003) pointed out that women reporting sexual offences ought to be afforded greater assistance to entice more women into becoming witnesses in such proceedings if they knew they would not be exposed to massive embarrassment and humiliation.\n\n1.10.2 Australia\n\nSome of the victim centered approach adopted in Australia are as follows:\n\ni.) Victim Impact Statement (VIS)\n\nA VIS is a declaration from a victim of crime and his/her family regarding the effects of crime on them (Clarke, Davis, & Bookyes, 2003). Hence, the VIS is one of the primary models of the victimology approach to the criminal justice system. Nonetheless, it was found to differ in the application and extent of common law jurisdiction. This enables victims to describe the impact of the emotional, physical, emotional, and economic conditions of the crime committed to them through VIS (Clarke, 2003). According to Erez, these statements reveal the emotional, physical, and economic impacts of crime, according to the views of victims. Some of the arguments raised regarding the application of VIS within the criminal justice system of victims are as follows. While there are some schools of thought that support the use of VIS, there are others that do not. The protagonist school of thought asserts that VIS may have an impact on court dispositions and, hence, increase the use of restitution and compensation (Johnson & Morgan, 2008). They also argued that a positive result could be beneficial for the healing of victims.\n\nThe antagonist school of thought argues that victims’ state of mind may override objective sentencing based on sentencing guidelines and uniformity. Ashworth (Erez & Roeger, 1999) criticized the use of VIS to overcome the strength that it challenges fundamental principles of an adversarial system. In addition, the antagonist school concludes that it may cause unacceptable pressures on the court, particularly in high-profile cases.\n\nDespite these controversies, the study argues that VIS would act as a guide to judges in determining the probative value in any sentence to be given. The VIS necessary does not impose on the judge what to do but will provide directions on how to ameliorate the pain and suffering of the victim while holding the offender accountable. Judges must understand that justice is a two-way traffic and must not act in a sentimental manner.\n\nii.) State-driven and government funded responses to sexual assault\n\nSome of these measures include providing specialist Crisis Care Units in hospitals to deal with the response of victim/survivor of SA and Quality of care of medical, police, forensic services, and counselling services. Others include increased police training and the introduction of a Code of Practice for investigations, creation of Sexual Assault and Child Abuse Units (SOCITs), and Sexual Assault and Child Abuse Investigation Teams (SOCITs). In the court system, reforms have included the implementation and expansion of witness facilities for children and vulnerable witnesses – Court Network; Children giving evidence/testimony through video link; victim personal statements where the impact of an incident can be considered by the judge when sentencing; Specialism courts and specialized prosecution; and limitation in available cross-examination information.\n\n\n2. Conclusion\n\nWithin various jurisdictions, criminal justice reforms have been made to improve the substantive, evidentiary, and procedural rules of the system in the hope that it would effectively tackle cases of Sexual Violence. From the fore-going, it can be deduced that victims need a legal remedy that will enable them to heal, be validated, and empower. Hence, there is a need to make provisions for more effective alternative responses to the evaluated justice interests and needs of the victims.\n\nHaving examined a few of the interventions in South Africa and Australia, the following are recommended:\n\ni.) Victims need to be encouraged to seek medical or psychosocial support from surgeons, therapists, and counsellors.\n\nii.) Therefore, there is a need for more awareness and sensitization in the society through structuring at the federal, state, and local government levels.\n\niii.) Nigerian legislation should adopt the use of victim impact statements in our criminal justice system for cases of sexual violence.\n\niv.) Multi-sectoral and government-supported solutions related to sexual violence should be available to include well-coordinated medical, police, forensic, and counselling services for victims in accordance with the quality of care standards.\n\nv.) Enactment of a rape shield provision in any of our laws that concerns the offence of sexual violence, perhaps through legislation.\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nNo data associated with this article.\n\n\nAcknowledgement\n\nAuthor roles: IZU CC, Conceptualization, Formal Anaysis, Funding Acquisition and Writing of Original Article; FABAMISE S, Review and Editing; OYEWOLE O, Review and Editing.\n\n\nReferences\n\nAdministration of Criminal Justice Act, 2015: Violence against Persons and Prohibition Act. 2015.\n\nBabb BA, Wexler DB: Therapeutic Jurisprudence. Encyclopedia of Criminology and Criminal Justice. 2018; 5211–5292.\n\nBlack Law Dictionary: St. Paul MMN West Publishing Co:2004.\n\nBraithwaite J, Daly K: Masculinities, Violence and Communitarian Control.Just Boys Doing Business?Routledge; 2013.\n\nClark H: ‘What Is the Justice System Willing to Offer?’: Understanding Sexual Assault Victim/Survivors’ Criminal Justice Needs. Family Matters. 2010: 28–37.\n\nClarke D, Davis L, Bookyens K: A Silver Era for Victims of Crime Reassessing the Role that VIS can play in Improving Victims Involvement in Criminal Justice Procedures. Acta Crimilogica. 2003; 1692: 44.\n\nCoker D: Enhancing Autonomy for Battered Women: Lessons from Navajo Peacemaking. Ucia Law Review. 1999; 47: 1.\n\nCunneen C, Hoyle C: Debating Restorative Justice. Bloomsbury Publishing; 2010. Publisher Full Text\n\nCuomo MM: The Crime Victim in a System of Criminal Justice. Journal of Civil Rights and Economic Development. 1992; 8(1).\n\nDaly K, Curtis-Fawley S: Gendered violence and restorative justice: the views of victim advocates. Violence Against Women. 2005; 11(5): 603–638. Publisher Full Text\n\nDaly K: Conventional and innovative justice responses to sexual violence. Melbourne: Australian Institute of Family Studies; 2011.\n\nDaly K: Remarking Justice after Sexual Violence: Essay in Conventional. Restorative and Innovative Justice. The Hague: Eleven International Publishing; 2022.\n\nDaly K: Sexual violence and Victims’ Justice Interests. Restorative Responses to Sexual Violence: Routledge; 2017. Publisher Full Text\n\nDaly K, Marchetti E: Innovative Justice Processes: Restorative Justice, Indigenous Justice and Therapeutic Jurisprudence.Marmo M, De Lint W , Palmer D, editors. Crime and Justice: A guide to Criminology. 4th Edition.Thompson Reuters; 2012.\n\nDe Veauuse Brown NF, Annor FB, Swahn MH, et al.: Sexual Violence Experience among Nigerian Girls and Young Women: What are the Roles of Early Sexual Debut, Multiple Sex Partnerships, and Traditional Gender Role Beliefs? Journal of Interpersonal Violence. 2022; 37(5-6): NP2747–NP2767. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDecker MR, Wood SN, Kennedy SR: Adapting The Plan Safety App To Respond To Intimate Partner Violence For Women In Low- And Middle-Income Country Settings: App Tailoring And Randomized Controlled Trial Protocol. BMC Public Health. 2020; 20: 808. Publisher Full Text\n\nDurant W: The Story of Philosophy. New York: Washington Square Press; 1961.\n\nEdwards A, Haslett J: Domestic Violence and Restorative Justice: Advancing the Dialogue.In 6th International Conference on RestorativeJustice, Vancouver, Bc; 2003.\n\nEjembi PA, Aina-Pelemo AD, Owo J, et al.: The trajectory of Nigerian law regarding sexual harassment in the workplace. Journal of Law and Human Rights. 2020; 4: 1.\n\nEjieke Maduka v Microsoft Nigeria Limited and 3 Ors.2012.\n\nErez E, Roeger L: The Effect of Victim Impact Statements on Sentencing Patterns and Outcomes: The Australian Experience. Journal of Criminal Justice. 1999; 23(4): 363–375. Publisher Full Text\n\nFreckelton I: Therapeutic Jurisprudence Misunderstood and Misrepresented: The Price and Risks of Influence. Thomas Jefferson Law Review. 2008; 30: 575–751.\n\nGarner BA: Black’s Law Dictionary.Thomson Reuters; 2014.\n\nHerman JL: Justice from the victim’s perspective. Violence Against Women. 2005; 11(5): 571–602. Publisher Full Text\n\nHudson B: Restorative Justice and Gendered Violence: Diversion or Effective Justice? British Journal of Criminology. 2002; 42(3): 616–634. Publisher Full Text\n\nIliadis M: Adversarial Justice and Victims’ Rights: Re-conceptualizing the Role of Sexual Assault Victims. London: Routledge, Taylor & Francis Group; 2020a.\n\nIliadis M: Victim Representation for Sexual History Evidence in Ireland: A Step Towards or Away from Meeting Victims’ Procedural Justice Needs? Criminology & Criminal Justice. 2020b; 20(4): 416–432. Publisher Full Text\n\nIliadis M, Flynn A: Providing a check on prosecutorial decision-making: An analysis of the victims’ right to review reform. The British Journal of Criminology. 2018; 58(3): 550–568. Publisher Full Text\n\nImiera PP: Therapeutic Jurisprudence and restorative justice: healing crime victims, restoring the offenders. De Jure Law Journal. 2018; 51(1). Publisher Full Text\n\nJago v. District Court of New South Wales (1989) 168 CLR 23.\n\nJameelah O, South Africa’s rape Shield: Does section 227 of the Criminal Procedure Act affect an accused’s fair trial? SACJ. 2016; 1–23. Accessed 27 March 2024. Reference Source\n\nJohnson MI, Morgan EF: Victim Impact Statements: Fairness to Defendants? (From Controversies in Victomology, Second Edition NCJRS Virtual Library 225289). 2008; pp. 115–131.\n\nJordan J: Serial survivors: Women’s Narratives of Surviving Rape. Sydney: The Federation Press: 12; 2008.\n\nKaribi JW: National Policy on Compensation to Victim of Crime; How desirable. Federal Ministry of Justice, Lagos; 1990.\n\nKelly DP: ‘Victim’s Reaction to The Criminal Justice Response’, Paper Prepared for The Annual Meeting of The Law and Society Association, Toronto, 1982. 2020.\n\nKing M, Freiberg A, Batagol B, et al.: Non-Adversarial Justice.Federation Press; 2014.\n\nKoss MP, Bachar KJ, Hopkins CQ, et al.: Restorative Justice For Sexual Violence: Repairing Victims, Building Community, And Holding Offenders Accountable. Annals of the New York Academy of Sciences. 2003; 989(1): 384–396. Publisher Full Text\n\nManty P: Personalizing Crime: Mediating Produces Restorative Justice and Offenders American Bar Association: Dispute Resolution Magazine; 2001.\n\nNaylor B: Effective Justice for Victims of Sexual Assault: Taking Up the Debate on Alternative Pathways. University of New South Wales Law Journal. 2010; 33: 662.\n\nO’Connell M: The evolution of victims’ rights and services in Australia. In Crime, Victims and Policy: International Contexts, Local ExperiencesLondon: Palgrave Macmillan UK; 2015.\n\nOjo E, Annad R, Noureddine I: How can victims centered approach address Sexual Violence. Accessed on 11th September 2021. Reference Source\n\nPali B: Towards Integrative Frameworks For Addressing Sexual Violence: Feminist, Abolitionist Social Harm And Restorative Perspectives. In Restorative Responses to Sexual Violence: Routledge; 2017. Publisher Full Text\n\nPedersen L: Moving Bodies as Moving Targets: A Feminist Perspective on Sexual Violence in Transit. Open Philosophy. 2020; 3(1): 369–388. Publisher Full Text\n\nPeterson C, DeGue S, Florence C, et al.: Lifetime Economic Burden of Rape among US Adults. American Journal of Preventive Medicine. 2017; 52(6): 691–701. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPradeep S: Victims and victimization: Process and Healing.2015. Accessed on 11 March 2024. Reference Source\n\nPrinsloo v Bramley Children’s Home [2006] JOL 17236 (T) at 19.\n\nProsecutor v. Thomas Lubanga Dyilo, ICC-01/04-01/06-1119, decision on victims’ participation, paras 90-92 (18 January 2008).\n\nS v. Mothopeng 1979 SA 180 (T).\n\nS v. Matyityi (2011 (1)) SACR 40 (SCA).\n\nS v. Staggie 2003 (1) BCLR 43 (C) at 44.\n\nSardina A, Ackerman A: Restorative Justice in Cases of Sexual Harm. The City Of New York. Review. 2022; 25: 1.\n\nSGBV, FG to Review 2017 National Policy on Justice – News Agency Nigeria. Accessed on 11 September 2023. Reference Source\n\nSmythe D: Moving beyond 30 years of Anglo-American rape law reforms: Legal representation for victims of sexual offences. SACJ. 2005: 18.\n\nState of Punjab v. Saurabh Bakshi (2015) 5 SCC 18. 2\n\nThursday NN, Duson NA: The concept of Justice and Its Application in a Developing Country such as Nigeria. International Journal of Innovative Legal and Political Studies. 2021; 9(1): 52–62.\n\nUmbreit MS, Bradshaw W, Coates RB: Victims of Severe Violence Meet The Offender: Restorative Justice Through Dialogue. International Review of Victimology. 1999; 6(4): 321–343. Publisher Full Text\n\nUN Women, ‘Victim Centered Approach’ 14 January 2019. accessed on 12 December 2024. https://www.endvawnow.org/en/articles/1790-victim-survivor-centere-approach.html\n\nUnited Nations Human Rights Declaration of Basic Principles of Justice for Victims of Crime and Abuses of Power, 1985, no. 4. accessed on 12 May 2024. www.ohchr.org/en/instruments-mechanisms/instruments/declaration-basic-principles-justice-victims-crime-and-abuse#:text=Judicial and administrative mehanisms through should, seeking redress through such mechanism\n\nVan Der Merwe A: Addressing Victims’ Harm: The Role of Impact Reports. T. Jefferson L. Rev. 2007; 30: 391.\n\nViolence against Persons and Prohibition Act, 2015.\n\nWexler DB: Inducing Therapeutic Compliance through the Criminal Law. Law and Psychology Review. 1990; 14(43).\n\nWilson D: Therapeutic Jurisprudence in Criminal Justice: The Price of Letting One Hundred Flowers Bloom. Eur. J. Curr. Leg. Issues. 2021; 25(1): 23.\n\nZehr H: Retributive justice, restorative justice.Johnstone G, editor. A Restorative Justice Reader: Text, Sources, Context.Willan Publishing: Cullompton, UK; 2003. Publisher Full Text\n\nZernova M: Restorative Justice: Ideals and Realities. Routledge; 2016.\n\nZinsstag E, Keenan M: Restorative Responses to Sexual Violence. Restorative Responses to Sexual Violence: Legal, Social and Therapeutic Dimensions. 2017; 17: 1."
}
|
[
{
"id": "343799",
"date": "05 Dec 2024",
"name": "Masahiro Suzuki",
"expertise": [
"Reviewer Expertise Restorative justice"
],
"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 manuscript addresses a timely topic, it requires significant revisions.\nThe manuscript's title suggests that the research focuses on victims of sexual violence in Nigeria. However, the specific problems within the Nigerian criminal justice system are not clearly articulated, nor is it apparent how the manuscript proposes to address these issues. To improve clarity, the authors should explicitly define the scope of the research and the central challenges the manuscript seeks to address. This requires streamlining the literature review to include only relevant studies that directly inform the focus of the manuscript. Currently, the literature review is overly generic and lacks specificity, which dilutes its contribution to the topic.\nThe methodology section requires substantial clarification. While the abstract states that the study employs a doctrinal research methodology, the manuscript does not provide sufficient detail on how secondary sources were collected or their integration into the analysis. The authors should outline the process for selecting and reviewing secondary sources, such as legal documents, statutes, case law, or academic commentaries. Additionally, it is important to demonstrate how these sources inform the arguments and findings presented within the manuscript. This will lend credibility and structure to the methodology.\nThe conclusion is notably brief and does not sufficiently connect the findings to actionable recommendations. The authors should expand the conclusion to clearly articulate how their proposed recommendations could contribute to improving the Nigerian criminal justice system's response to victims of sexual violence. This may involve discussing practical implications, policy reforms, or specific interventions that could address the identified challenges.\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?\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": []
}
] | 1
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https://f1000research.com/articles/13-1288
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https://f1000research.com/articles/13-1286/v1
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28 Oct 24
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{
"type": "Research Article",
"title": "Assessment of water quality in the piped water supply system by using Water Quality index method",
"authors": [
"Kshyana Prava Samal",
"Ashok Kumar Tarai",
"Ashok Kumar Tarai"
],
"abstract": "Background Drinking water of the right and approved quality is a basic requirement for the development of any civilization. According to SDG 6 it is crucial to provide every citizen with equitable water quality and quantity.\n\nMethods The study area is the smart city of Bhubaneswar with 67 wards and three zones: the north zone, south-west zone, and south-east zone with around 12.4 lakh population. To maintain the water quality in the supply pipeline in this city, which is always assumed to be safe, it needs to be examined within certain time intervals to check the contamination. In this context, studies on water quality parameters in the supply pipeline network from different anticipated vulnerable areas have been collected for testing. In this context, water samples were collected from areas near industries, market complexes, educational institutions, and construction sites of each ward of Bhubaneswar. Nearly 10 water quality parameters were tested and analyzed using the weighted arithmetic water quality index method. This method takes input of all the parameters and provides the overall water quality index value, which classifies the water in different grades like excellent, good, poor, and very poor quality.\n\nResults According to the WHO (2011) guidelines, the study found that there is a deviation in the parameters like 10.78% in pH, 19.48% in dissolved oxygen, 43.88% in conductivity, and 22.95% in hardness from the standard limit, but the overall water quality index indicates the water is not in the poor and very poor range. Also, water quality index values identify that the water in the south-east zone is excellent compared to the north and south-west zones. The reason for the slight deterioration is due to the underground cable works, road works and also some areas where the old pipeline system is still existing due to personal encroachment of people as per Public health Engineering department.",
"keywords": [
"Drinking water",
"Heavy metal contamination",
"SDG 6",
"Supply water",
"Water quality parameter",
"Water quality index"
],
"content": "1. Introduction\n\nThe global water consumption has expanded, and this value will continue to increase over the next 50 years. To fulfill Goal 6 of the Sustainable Development Goals, which calls for universal access to clean water and sanitation, safe and reasonably priced drinking water must be provided by 2030. According to the Honorable Minister of Urban Development, Bhubaneswar topped the list of the top 20 smart cities out of 98 nominated cities. Bhubaneswar was selected under the Smart City Development Plan of the Indian Government. The primary mission of a smart city is to fulfill citizens’ desired aspirations in a smart and sustainable manner. Thus, it is worthwhile to determine the extent of water quality detrimental across the wards of Bhubaneswar and intervene in a suitable way to ensure that the SDGs are met. It has been observed that cities like Bhubaneswar with large populations depend more on surface water than on groundwater. Water quality can deteriorate during distribution because of several variables, including interactions within the bulk water or between the distributed water and pipe material (Kirmeyer et al. 2001). Furthermore, the breakdown of disinfectants, such as chlorine, can deteriorate the microbiological conditions of the distribution system, putting customers’ health at risk (Clark and Haught, 2005).\n\nDue to rapid urbanization, people’s concern for health issues, and the higher aspiration level of consumers in Bhubaneswar, the government has focused more on water supply for human consumption (Government of Odisha, 2013). Domestic water demand is growing dramatically in Bhubaneswar because of the twin phenomena of population growth and rural-urban migration, which enhance industrialization, market segmentation, construction, etc. Nowadays, owing to population growth, a huge gap is created between population and water sources, leading to the rapid expansion of various water networks. A potable piped water supply with access to good quality at a low cost, equitable, sustainable, and environmentally acceptable is urgently needed. The aging and deterioration of pipeline systems in the distribution has now become a challenge to overcome (Shannon et al., 2008).\n\nAlthough the piped water supply has been implemented in Bhubaneswar, a mid-sized city and state capital of Odisha, India, the question arises as to whether equity in quality with real sense has been achieved. Because the public comes from a variety of professional backgrounds, it is important to raise awareness about the quality of the water supply (Nasirian, 2007). The water quality index (WQI), which was initially developed by Horton in 1965, has been widely used by many researchers. The WQI is an all-inclusive instrument that combines several supply water chemical constituents in a comprehensible format. This is accomplished by using an aggregation function and selectively weighing the water quality factors (Abtahi et al. 2015). Moreover, the Water Quality Index (WQI) has demonstrated efficacy in disseminating water quality data to decision makers, as evidenced by its extensive implementation in numerous water quality assessment (Batabyal and Chakraborty, 2015; Chen et al., 2019).\n\nThe Water Quality Index (WQI), frequently employed by researchers in developing nations, utilizes the Weighted Arithmetic Water Quality Index Method (WAWQIM). This strategy is especially common in areas with inadequate infrastructure for comprehensive data collection (Yogendra & Puttaiah 2008). This study employed the Water Quality Index (WQI) as a tool to scrutinize water quality and its variations.\n\nAssuming that the piped water supply system is consistently of high quality and safe, several investigations on its quality have been conducted. We measured some of the critical quality characteristics at 335 locations that received piped water supply in order to determine the answer to this issue. The water quality parameters studied include hardness, pH, chloride, dissolved oxygen (DO), alkalinity, electrical conductivity (EC), total dissolved solids (TDS), biochemical oxygen demand (BOD), nitrate, sulfate, lead, copper, and zinc.\n\nFew studies on the quality measurement of supply water have assumed that supply water quality deteriorates with the aging of infrastructure, type of pipe materials, and the combination of wastewater and drinking water (Liu et al., 2017). Potable water needs to maintain its quality according to the guidelines of the World Health Organization (WHO, 2011) and BIS (Bureau of Indian Standards: IS 10500:2012). Sometimes, these factors may lead to a loss in the quality of the piped water supply. It was observed that most of the leak points were detected as damages and cracks owing to the laxity of contractors during installation and pipe fittings. In addition, most of the leak points were detected at the connection points of couplings, elbows, valves, and saddle clamps. Backfilling and bedding sand containing large and sharp stones causes pipes and fittings to scratch and puncture (Qahtani et al., 2020). Furthermore, it was also found that the water quality deteriorated when synthetic materials were used in water pipes, particularly when trace organics were leached out by the flowing water. After testing, the presence of carbon tetra chloride (CTC), toluene, chloroform, styrene, and O-xylene were also detected in the water pipeline system (Shaikh et al., 2019). The variation in dissolved oxygen is directly related to the corrosion rate through redox couple reactions in pipeline systems. Dissolved oxygen consumption is related to pipeline materials such as copper, steel, and iron (Vargas et al., 2010).\n\nBiochemical oxygen demand was used to calculate the total amount of oxygen consumed over an extended period of time by bacteria and other microorganisms involved in stabilizing decomposable organic matter. Biochemical oxygen demand tests are widely used to assess the effects of effluents from sources, such as pulp mills, municipal wastewater treatment facilities, feedlots, and vegetation used in food processing, which can include large amounts of biodegradable organics. According to Dey et al. (2021), an increased oxygen demand indicates the possibility of an increase in dissolved oxygen as the organic content in the sewage is oxidized by macrobiotics. The extremely low oxygen demand indicates the presence of toxic or nonbiodegradable contaminants in pure water. When the biochemical oxygen demand of drinking water ranges from 1 to 2 ppm, it is considered reasonably clean; when it falls between 3 and 5 ppm, it is considered moderately clean. The biochemical oxygen demand of contaminated water is 6–9 ppm. A high level of pollution is indicated by a biochemical oxygen demand of more than 10 ppm in water (Koda et al., 2017).\n\nCorrosion and water quality degradation in water distribution systems are significantly influenced by the pipe type used. A combination of unlined cast iron pipes and galvanized pipes was used to study the characteristics of the deposited scale and water quality in the water distribution system. Bench testing was conducted to assess water quality parameters, such as pH, dissolved oxygen (DO), oxidation and reduction potential, alkalinity, conductivity, turbidity, color, Fe2+, and Zn2+. It was found that the significant effect of the pipe material on the corrosion scale characteristics leads to water quality variation. Iron, which is primarily released as ferric particulates from pipe lines, affects pH and alkalinity levels (Li et al. 2016). Learbuch et al. (2021) observed the impact of pipe material on the microbial population and biofilm development in semi-stagnant conditions. It was deduced that pipe material plays an important role in the growth of biomass concentration, the increase of specific microorganisms, and the bacterial community composition in the distribution system with unchlorinated drinking water.\n\n\n2. Methods\n\nBhubaneswar is situated at 20 °12 n to 20 °25’ N latitude and 85 °44’E to 85 °55’E longitude across the main axis of eastern Ghats in the Khordha district of Odisha on the western flange, as shown in Figure 1a (also refer underlying data). Bhubaneswar is the capital city of eastern Odisha. The rich heritage associated with the city, the spread of religious spots (Bhubaneswar is referred to as Temple City), contemporary acknowledgement as an education, and IT hub have contributed significantly to the growth and publicity of the city.\n\nThe BMC (Bhubaneswar Municipality Corporation) has separated the city of Bhubaneswar into three zones. There were 21 wards in the north zone, 21 in the south-west zone, and 25 in the south-east zone. The total population in all of these wards was approximately one million. The study concentrated on piped supply water in the northern, South-West, and South-East zones of Bhubaneswar, which comprises 67 wards, as per Bhubaneswar Municipal Corporation (BMC, 2011). The supply water sample collection areas were emphasized, keeping the following vulnerable areas in mind: industrial areas, market complexes, high-density populations, construction sites, and academic institutions. The water quality parameters for Bhubaneswar were tested zone-wise in the laboratory according to the guidelines stated in the BIS (Bureau of Indian Standards: IS 10500:2012). Water samples were taken at random from the 67 wards listed above, and the results are shown as ward-wise data. The detail flow chart of the process is mentioned in the Figure 1b. In each ward, five locations were selected, keeping in mind the areas with the presence of more population, new ongoing constructions, more academic institutions or industries, and the presence of market hubs. The areas were selected keeping in mind that there is a greater chance of contamination in comparison to other areas due to the multiusers in one place and the chance of more wear and tear, corrosion, leakage, etc. of the water pipeline system.\n\nThese parameters were selected by reviewing previous studies on the quality of potable water. Supply water samples were collected with a sample size of approximately 335 from different locations and two samples from the same location. The samples were kept at approximately 5 °C in glass bottles with a one liter capacity for analysis. From each location, two water samples were collected in clean screw-tight bottles. The testing procedure followed the American Public Health Association (APHA) book. Parameters such as sulfate, nitrate, lead, copper, and zinc were obtained from the State Pollution Control Board Laboratory in Bhubaneswar. Physicochemical parameters, including pH, dissolved oxygen, conductivity, alkalinity, hardness, chloride, total dissolved solids, biochemical oxygen demand, sulfate, nitrate were tested using the standard methods in APHA (1926). The weighted arithmetic index approach was used to calculate the water quality index by considering the average value of each parameter (Brown et al., 1970).\n\nBhubaneswar City mostly depends on surface water sources such as the Mahanandi, Kuakhai, and Daya rivers. The intake points are located on the banks of these rivers. There are multiple water treatment plants (WTP) with a capacity of millions of gallons per day (MGD) that supply treated water to Bhubaneswar City. Thereafter, the treated water is transmitted to the mass-balancing reservoir, the underground reservoir (UGR), which is pumped to the elevated service reservoir (ESR). House-level connections receive water from elevated service reservoirs through gravity. A schematic of these sources is presented in Figure 2.\n\n2.1.1 Use of ArcGIS Software for identification of contaminated areas\n\nThis study applied ArcGIS software to identify the topographical features of possible contaminated areas through spatial analysis and visualization. The advanced functionalities of ArcGIS facilitate a comprehensive understanding of environmental degradation and strengthen environmental management strategies. To explore the spatial variation in water quality parameters over the area of Bhubaneswar, the inverse distance weighted interpolation technique was used to produce different maps using the ArcGIS tool with scaling of the concentration of water quality parameters.\n\n2.1.2 Interpolating surfaces in ARCGIS by Inverse distance-weighted interpolation (IDW)\n\nArcGIS Spatial Analyst offers several interpolation tools for generating surface grids from point data. IDW method is used, when the set of points are dense enough to capture the extent of local surface variation needed for analysis. This is one of the simplest and most readily available methods. The method assumes that a weighted average of values at points within a certain cut-off distance or from a given number m of the closest points (typically 10 to 30) can approximate the value at an unsampled point. Weights are usually inversely proportional to a power of distance (Sajil Kumar & Kuriachan, 2022; Watson, 2013), which is shown in Equation 1.\n\n2.2.1 Calculation of Water Quality Index\n\nThe WQI was determined using drinking water quality criteria recognized by the Bureau of Indian standard (BIS) and the World Health Organization (WHO). According to Oni and Fasakin (2016), the WQI approach is a useful tool for educating the public and policymakers about the quality of the water. It is a unambiguous tool that makes it possible to integrate water metrics that are crucial for the water quality. Here ten parameters like pH, dissolved oxygen, conductivity, alkalinity, hardness, chloride, total dissolved solids, biochemical Oxygen demand, sulphate and nitrate are considered for calculation of water quality index. Parameters like lead copper and zinc are excluded from the calculation because these values are below the range of detectable limit. Given these conditions, the weighted arithmetic index approach (Brown et al., 1970) is utilized in this work to compute the WQI, which is the most appropriate technique to assess the impact of pollution on supply water.\n\nThe Water Quality Index (WQI) (Inayathulla et al., 2013) is given as:\n\nWhere,\n\nqi = quality rating of ith water quality parameter\n\nwi = unit weight of ith water quality parameter ≃ 1; and qi relates the value of the parameter in polluted water to the standard permissible value i,e. qi=100(vi−vi0si−vi0)k=1∑i=1n1si\n\nWhere, vi = estimated value of the ith parameter,\n\nvio = ideal value of the ith parameter\n\nsi = standard permissible value of the ith parameter as per IS 10500\n\nIn most of the cases, vio = 0 except for pH and dissolved oxygen\n\nFor pH, vio = 7 and for dissolved oxygen, vio = 14.6 mg/l\n\nThe unit weight (wi), which is inversely proportional to the values of the recommended standards is obtained\n\nas: wi=ksi, Where k=1∑i=1n1/si\n\nThe rating of the water quality using the above method is shown in Table 1.\n\n\n3. Results and Discussion\n\nThe statistical summary of water quality parameters and their comparison with the permissible limits indicate that the percentage of samples deviating from the permissible limit as per IS 10500 (2012) are shown in Table 2. The water quality parameters were plotted for the three different zones using box-whisker plots, as illustrated in Figure 3-a, b, c, d, e, f, g, h, i, and j. The corresponding maps with vulnerable and safe areas are shown in Figures 4–13 (refer underlying data).\n\nTable 2 represents the pH levels, with a standard deviation ranging from 0.48 to 0.70 across zones, which demonstrates moderate variability, while the average pH values fall within the recommended range of 6.5 to 8.5. The percentage of samples exceeding the permissible limit was minimum in the southeast zone, that is, 6.40%, and the maximum variation was 13.33% in the southwest zone. Dissolved oxygen levels exhibited moderate variability, with standard deviations ranging from 0.49 0.54. Despite the average values being within the acceptable range of 6.5-8 mg/l. The percentage of samples exceeding the permissible limit was minimum in the southeast zone, that is, 15.20%, and the maximum variation was 21.90% in the south-west zone. Electrical conductivity values, with standard deviations ranging from 73.69 to 90.63, indicate considerable variability in mineral content across zones. While the average electrical conductivity values generally align with the guidelines, the percentage of samples exceeding the permissible limits has a minimum of 27.61% in the southwest zone and a maximum of 72% in the southeast zone. These parameters exhibited varying levels of variability and adherence to guidelines across zones. Hardness and total dissolved solids showed significant standard deviations ranging from 40.78 to 60.24 and from 47.90 to 58.91, respectively, indicating substantial variability in mineral content. The minimum variation in hardness was 44.8% in the east zone and a maximum of 10.47% in the southwest zone. The percentage of samples exceeding permissible limits varied widely across parameters and zones, highlighting the complexity of water quality management. Parameters such as alkalinity, hardness, chloride, total dissolved solids, biochemical oxygen demand, sulfate, and nitrate were within permissible ranges. As shown in Figure 3, a comparative analysis was performed for various water quality parameters across three distinct geographic zones: north, south-west, and south-east. Each box-whisker plot represents the distribution and central tendency of a specific parameter within the zones.\n\nFrom Table 2 and Figure 3(a) (refer underlying data), it is found that the Bhubaneswar piped supply water has a pH range of 5.56 to 8.61 in both the north and south-west zones, whereas it is 6.23 to 8.59 in the south-east zone. The average values of all three zones were 7.66, 7.73, and 7.56, respectively, indicating that the supply water was slightly alkaline. The contents of hydroxides, carbonates, and bicarbonates primarily regulate the alkalinity of the groundwater (Sajil Kumar et al., 2013). Piped supply water samples exceeding the permissible limit were 12.62%, 13.33% in the south-west zone, and 6.4% in the south-east zones, respectively. The standard deviation was 0.48 to 0.70, which indicates that the value clustered tightly to the mean. Figure 3(a) represents the areas that are more affected by pH: Damana Area of Ward No. 8 and Indradhanu Market Area of Ward No. 27, whose pH values were 8.61. Areas with acidic water have also been detected, such as Sriram Nagar of Ward No. 59, Swadhin Nagar of Ward No. 34, and Pancha Sakha Nagar of Ward No. 64, with pH values of 5.56, 5.74, 5.74 and 5.56, respectively. The results show that the areas that are affected by this variation in pH are expected to be affected by factors such as the old age of supply pipes (more than 40 years) due to a lack of maintenance and many newly constructed underground sewerage systems, which cause contamination in the pipeline system (Eun et al., 2011).\n\nDissolved oxygen values are a significant indicator of water quality and organic pollution in water bodies. Dissolved oxygen had average values of 7.5, 7.54, and 7.43 in the north, south, west, and southeast zones, respectively. There is a deviation of dissolved oxygen values of 21.35%, 21.9%, and 15.2% from the permissible range in the northern, South-west and South-east respectively, as shown in Table 2 and Figure 3(b). In addition, it was found that there were some areas with dissolved oxygen values less than 6 mg/l, such as Sikharchandi Nagar of Word No. 2, Shakti Vihar of Ward No. 20, Shree Vihar of Ward No. 22, Dumduma Phase 3 of Ward No. 64, and Jharapada High School Area of Ward No. 42, as presented in Figure 5 Ward wise dissolved oxygen in supply water of Bhubaneswar, refer underlying data. Typically, polyphosphates are coated inside municipal water supply pipes to shield the metal from oxygen exposure, resulting in high dissolved oxygen concentrations (Sarin et al., 2004).\n\nIt is well understood that the electrical conductivity of water determines the minerals and salts that are dissolved in the water. Electrical conductivity ranges from 58.25 s/cm to 480 s/cm in the north zone, 67.7 s/cm to 519.9 s/cm in the South-West zone, and 173 s/cm to 581.47 s/cm in Bhubaneswar’s South-East zone, respectively. As shown in Figure 6 and Figure 3(c), in the north zone, 32.03% of the samples, 27.61% in the south-west zone, and 72% in the south-east zone are beyond the permissible limit. Some areas had a conductivity higher than 500 μs/cm: Sir Pu Bhoi Sahi of ward no. 51, Nico Park Lake area of ward no. 28, Bhoi Sahi of Ward no. 28, Gridco Colony of ward no. 29, Sarala Nagar, and Santoshi Nagar of Ward no. 31, as shown in Figure 6 Ward wise electrical conductivity in supply water of Bhubaneswar Refer underlying data. Runoff water, septic systems, animal waste, and sewage leakage into the ruptured old pipeline system are the causes of this The alkalinity values of the different areas presented in Figure 3(d) indicate that in all three zones, the data are below the permissible limit. Low values of alkalinity were observed in the southeast zone and high values in the northern zone. As shown in Figure 7 (refer underlying data) Ward wise alkalinity in supply water of Bhubaneswar, no areas were affected by the alkalinity.\n\nHardness concentration varied between 13.12 mg/l and 262.2 mg/l in the north zone, 13.12 mg/l to 229.6 mg/l in the south-west zone, and 98.4 mg/l to 268.96 mg/l in the south-east zone, with an average value of 118.45 mg/l, 116.96 mg/l, and 186.09 mg/l, respectively, presented in Table 2 and Figure 3(e). The presence of cations such as calcium, magnesium, iron, aluminum, and other bivalent and trivalent cations is the cause of water hardness (Malakootian et al., 2010). Supply of water with a high hardness level results in a poor taste of water. Furthermore, persistent use of an aberrant concentration in humans might result in kidney stones and cardiovascular issues (Chaudhary and Satheeshkumar, 2018). The highest deviation in hardness was found in two areas: Champa Pokhari of ward no. 45 and Rabindra Mandap of ward no. 36. These are the maximum values of the hardness of the supply water in Bhubaneswar, as shown in Figure 8 (refer underlying data) Ward wise hardness in supply water of Bhubaneswar.\n\nChloride infiltrates supply water systems through a combination of natural processes, such as soil erosion, geological weathering, and human activities, such as fertilizer usage and wastewater discharge (Clesceri, 2012). In the North zone, the mean chloride level is recorded at 33.86 mg/l, while in the South-West zone, it slightly increases to 34.29 mg/l, and in the South-East zone, it further rises to 38.84 mg/l, as illustrated in Figure 3(f). The standard deviation values for chloride vary across zones, with the north zone exhibiting 11.65, the South-West zone at 10.76, and the South-East zone at 7.61. These deviations indicate the extent of variability in the chloride levels within each zone. Remarkably, Figure 9 Ward wise chloride in supply water of Bhubaneswar (refer underlying data), shows no deviation from the permissible limit, confirming the safety of the Bhubaneswar water supply in terms of chloride contamination.\n\nTotal dissolved solids in the supply water varied between 37.86 mg/l and 312.2 mg/l in the north zone, 44.01 mg/l to 337.94 mg/l in the South-West zone, and 112.565 mg/l to 377.96 mg/l in the South-East zone, as per Figure 3(g). The average concentration of the supply water samples of 67 wards of Bhubaneswar was 166.02 mg/l, 163.16 mg/l, and 222.93 mg/l in the above-mentioned three zones, respectively. This demonstrates that the overall quality of the supply water is below the permissible level of 500 mg/l (IS 10500, 2012). In Figure 10 (refer underlying data) Ward wise Total dissolved solids in supply water of Bhubaneswar, it is demonstrated that no total dissolved solid value has exceeded the permissible limit.\n\nAs shown in Figure 3(h), the mean value in the three zones varies from 2.39 2.75. This indicates a relatively consistent range of values across the zones. According to Figure 11 Ward wise biochemical oxygen demand in supply water of Bhubaneswar (refer underlying data), all biochemical oxygen demand values fell within the allowed range. This suggests that the water quality in the measured zones met the specified standards or regulatory requirements, affirming the overall environmental health in those areas.\n\nAccording to IS-10500-2012 standards, the acceptable range for sulfate is set at 200 mg/l, with levels beyond 400 mg/l seeming harmful and potentially disease-causing if used for consumption. Various factors contribute to the presence of sulfate, including mineral dissolution, atmospheric deposition, and human activities such as fertilizer use and mining (Shengnan et al., 2021). The high sulfate levels found in many global aquifers are largely due to gypsum. The average value ranges between 15.57 mg/l and 17.14 mg/l in the three zones of Bhubaneswar. Figure 12 Ward wise sulphate in supply water of Bhubaneswar (refer underlying data), and 3(i) (refer underlying data) show that the sulfate value does not exceed the permissible limit.\n\nAccording to IS10500-2012 standards, the nitrate value range was set at 45 mg/l, representing the desired level, and all samples fell within the permissible limit. The maximum observed value was 30 mg/l in both the Southeast and Southwest zones, as illustrated in Figure 3(j). Adherence to regulatory standards is critical for ensuring water safety. The prevalence of high precipitation rates, which facilitate fertilizer infiltration, has been identified as the primary driver behind elevated NO3- values in the source of the supply water (Wagh et al., 2017, 2018). High concentrations of nitrate cause the blue baby syndrome (Elwood and van der Werf, 2022). Figure 13 Ward wise nitrate in supply water of Bhubaneswar (refer underlying data), (refer underlying data) indicates that Bhubaneswar supply water is safe in terms of nitrate contamination.\n\nFrom Table 3, it is observed that water quality is excellent and good in the supply water of the northern, south-west, and south-east zones of Bhubaneswar. The highest percentage of excellent water quality was found in the south-east zone of Bhubaneswar (28.58%), while the lowest percentage was found in the south-west zone (9.53%). The highest percentage of good water quality (90.47%) was found in the south-west zone of Bhubaneswar. The northern and south-east zone show 70-80% of a good water quality index. This is because the southeast zone has less human interference. The percentage of good quality is lower in the south-west zone than in others because many old pipeline networks still exist in these areas, as per the report of the Public Health Engineering Department (PHED). No signs of poor, very poor, or unsuitable water quality indices were found in any of the zones.\n\nAs shown in Figure 14 Comparison of water Quality Index of supply water in different zones of Bhubaneswar (refer underlying data), the overall water quality of Bhubaneswar is in good condition, although some parameters deviated slightly from their permissible limits. This is because of the large sample size in a greater number of areas, where the deviations in most of the parameters are within the permissible limit, and very few parameters, such as hardness and electrical conductivity, deviated in a slightly higher range from the permissible limit. However, it did not significantly affect the water quality index values.\n\n\n4. Conclusion\n\nThis study evaluated the overall water quality of supply water in different zones of Bhubaneswar, where the excellent water quality percentage was comparatively less than the percentage of good water quality. The south-west zone more areas are excellent water quality than north-zone and south-east zone. The study indicates that if the water supply network system is not properly monitored, future water quality deterioration will be a major issue. Suitable policies should be incorporated to address these issues in the future. A pipeline system of higher-grade material can be suggested where quality deterioration has already begun. Advanced technologies for the detection of faults in pipeline systems must be followed prior to water contamination.\n\n\nDeclarations\n\nAll authors critically evaluated the manuscript for intellectual content, approved the final version to be published, and agreed to be accountable for all aspects of the work.",
"appendix": "Data availability\n\nFigshare: Title: Research Raw Data files for supply water of Bhubaneswar, https://doi.org/10.6084/m9.figshare.26819056.v4 (Samal and Prava 2024).\n\nThis Project contains the following underlying data:\n\n• Volunerable Area maps using ArcGIS for all the 8 parameters and also Bhubaneswar Study area map (JPG format with 300 dpi)\n\n• Water Quality parameters in different zones and it’s comparison (JPG format with 300 dpi).\n\n• Excel Data of 10 parameters of 67 wards divided into three zones (.xls)\n\n• Excel Data of Water Quality Index calculation of 67 wards divided into three zones (.xls)\n\nData are available under the terms of the Creative Commons Zero ‘No Rights Reserved’ data waiver (CC0 Public domain dedication).\n\n\nReferences\n\nAbtahi M, et al.: A modified drinking water quality index (DWQI) for assessing drinking source water quality in rural communities of Khuzestan Province, Iran. Ecol. Indic. 2015; 53: 283–291. 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Publisher Full Text\n\nWagh VM, Panaskar DB, Muley AA: Estimation of nitrate concentration in groundwater of Kadava river basin-Nashik district, Maharashtra, India by using artificial neural network model. Model. Earth Syst. Environ. 2017; 3: 1–10. Publisher Full Text\n\nWatson D: Contouring: a guide to the analysis and display of spatial data. Elsevier; 2013.\n\nYogendra K, Puttaiah ET: Determination of water quality index and suitability of an urban waterbody in Shimoga Town, Karnataka. Proceedings of Taal2007: The 12th world lake conference. 2008; Vol. 342."
}
|
[
{
"id": "338598",
"date": "07 Jan 2025",
"name": "Taj Muhammad Jahangir",
"expertise": [
"Reviewer Expertise Water quality chemical assessment"
],
"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 am writing the following comments for the improvement of manuscript;\nThe manuscript is short and may be short communication. Overall each section needs improvements. The real objectives may given for to address within the introduction. Those tests conducted in present work, may only be basis of objectives. Table 2 guideline of EC is not mg/l, check other units and limits. The nitrate 30 mg/l is quite high in rivers, It may checked, the source of pollution in ice melt water. The source of water at within rivers that did not compared before wards. Inter river comparison may also present of three rivers. The methodology of parameters i.e nitrate may also explained. Therefore WQI within good quality is suspected and may checked. The results of analysis may compared for statistical analysis, i.e t-test, PCA, Hierarchal analysis, piper diagram, SAR for irrigation. The table for physico chemical parameters may also given supplementary. The discussion is very short and the number parameters were also less included, i.e metals. The abstract and conclusion should also improved. The results were not compared with local studies, and international rivers or water supply. Importance of water if any public water, dependency of type of people on supply water that did not given in detail. The nature of water in different wards may compared with other smart cities. Why samples crossed the limits, what was the reasons and how public awareness. Indicate the samples with GPS and contaminated samples. Indicate the mass balance and error. The spatial variation may also explained. Figures may improved with ranges to better view.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": []
},
{
"id": "348678",
"date": "13 Jan 2025",
"name": "Bouselsal Boualem",
"expertise": [
"Reviewer Expertise Fundamental Hydrogeology",
"Hydrogeochemistry",
"Water Drilling and Hydrodynamics",
"Groundwater Vulnerability and Management",
"Water Pollution",
"Hydrogeological Mapping",
"Aquifer Recharge and Potential Assessment."
],
"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\nFirst of all, thank you for inviting me to review this article \"Assessment of water quality in the piped water supply system by using Water Quality Index method\". After reading and analyzing it, here are my main observations:\nContent of the Article The article analyzes the quality of drinking water in Bhubaneswar, India, using the Water Quality Index (WQI). This study aligns with the Sustainable Development Goals (SDGs), particularly SDG 6, which aims to ensure universal access to safe and high-quality drinking water. The researchers collected and analyzed 335 water samples from three zones of the city (north, south-west, and south-east), covering 67 neighborhoods. Parameters such as pH, dissolved oxygen, electrical conductivity, and hardness were evaluated in accordance with WHO and Bureau of Indian Standards (BIS) guidelines. The results reveal that the water quality is generally good to excellent, with the south-east zone showing the best performance due to minimal human interference. However, some deviations from standards were observed, particularly in terms of pH and conductivity, mainly in areas with aging infrastructure or ongoing construction work. The authors recommend infrastructure improvements, enhanced monitoring, and the use of advanced technologies to prevent future water quality deterioration.\n\nStrengths of the Article The article stands out for its representative sampling, encompassing 335 samples from 67 neighborhoods, and its use of the Water Quality Index (WQI), which facilitates a comprehensive and understandable evaluation. It highlights disparities between the studied zones and identifies causes of degradation, such as aging infrastructure. Aligned with the Sustainable Development Goals, the study proposes practical recommendations, including pipeline upgrades and the use of advanced technologies. Its rigorous methodology, adherence to international standards, and transparent data presentation make it a valuable contribution to urban water quality management.\n\nRecommendations for the Authors 1. Abstract\nThe abstract should clarify the problem addressed by the study, its significance, and the method employed. Key findings should be highlighted concisely and quantitatively. For example, specifying the parameters with significant deviations and the percentage of affected zones would strengthen the impact of the results.\n2. Introduction\nThe novelty and specific contributions of the study should be clearly described and justified. Briefly compare the advantages of the proposed approach, such as the Water Quality Index (WQI), with existing methods. Although the study is specific to Bhubaneswar, demonstrate how its findings can be applied to other regions with similar contexts (e.g., rapid urbanization, aging infrastructure). Clarify the study's objectives and present them clearly at the end of the introduction.\n3. Methodology\nThe section \"2.1 Study Area\" should be limited to describing the geographical, social, and economic characteristics of the study area. Subsections on sampling and mapping should be separated for better clarity. The study does not address the bacteriological quality of water, a critical aspect for detecting contamination from wastewater, which poses a significant health risk.\n4. Results and Discussion\nPresent the chemical composition of reservoir water before its injection into the network to analyze changes during distribution. Describe the water treatment methods before distribution, as these can influence parameters such as hardness and chlorine concentration. Compare the findings with guideline values from the literature (Sawyer and McCarty, 1967; USEPA, 1994 for hardness; APHA, 2005 for TDS and electrical conductivity). Include scatter plots (e.g., TDS vs hardness) to highlight relationships between parameters. Add relevant indices to detect risks of scaling and corrosion in the distribution network (e.g., Langelier, Ryznar, Larson-Skold indices). Use a Piper diagram to determine the chemical facies of water and analyze its evolution within the network. Improve maps by adding scales and locality names for better readability.\n5. Conclusion\nInclude specific and practical recommendations for managing water distribution networks, such as modernizing infrastructure and using corrosion-resistant materials. Propose targeted policy interventions to ensure consistent drinking water quality, especially in regions facing similar challenges.\n6. References\nThe number of cited references is insufficient. More high-quality articles should be consulted, particularly on water quality assessment methods and risks related to chemical quality.\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": "350892",
"date": "13 Jan 2025",
"name": "Sudhir K Srivastava",
"expertise": [
"Reviewer Expertise Water Quality Ground Water Quality and Hydrochemistry"
],
"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 reported the analysis of Fe+2 and Zn2+ under Introduction para 8th, but no where the data of Fe+2 has been seen or utilized. APHA (1926) is very old version of the book the latest version is 2023 edition. The most of the chemical analysis has been done on out put point of piped supply, not the source point of water supply. so the BOD values are not appropriate as the supply water has travelled so much distance. It has not been cleared about the treatment of surface water before its supply.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1286
|
https://f1000research.com/articles/13-1023/v1
|
09 Sep 24
|
{
"type": "Case Report",
"title": "Case Report: Unveiling an anomalous diaphragmatic paraganglioma mimicking a hepatic tumor",
"authors": [
"Ermilo Echeverria Ortegon",
"Jose Luis Millet-Herrera",
"Javier Casillas",
"Jose Luis Millet-Herrera",
"Javier Casillas"
],
"abstract": "Abstract Paragangliomas are rare neuroendocrine tumors, often associated with catecholamine secretion. These tumors can arise in various locations, with the majority found in the abdomen and pelvis, while a smaller percentage occurs in the thorax and head and neck regions. Diaphragmatic paragangliomas are exceedingly rare, with only two documented cases in the literature. This report details a case of a primary diaphragmatic paraganglioma in a 59-year-old patient presenting with unexplained weight loss, tremors, and diaphoresis. Imaging studies revealed a mass in the right lobe of the liver, later identified as a diaphragmatic paraganglioma during surgery. The case underscores the importance of preoperative catecholamine assessment and careful surgical planning due to the risks associated with tumor manipulation. Complete surgical resection, although challenging, remains the definitive treatment, especially in hypervascular tumors located near major vascular structures.",
"keywords": [
"Paraganglioma",
"Catecholamines."
],
"content": "Introduction\n\nParagangliomas are uncommon tumors that develop from neuroendocrine cells located outside the adrenal glands. These tumors, which secrete catecholamines like norepinephrine, can be found in the pre-aortic and paravertebral sympathetic plexus or base of the skull, but they may also occur in the thorax, retroperitoneum, and pelvis.1 Among neuroendocrine tumors, 80-85% are pheochromocytomas, while only 15-20% are paragangliomas.2\n\nWhereas paragangliomas can develop in any paraganglia of the autonomic nervous system, they are more commonly found in the para-aortic region below the diaphragm and are less frequent in the thoracic area. Primary paragangliomas in the diaphragm are extremely rare. Although these tumors are generally benign, a small proportion can become malignant (10-20%) and metastasize. Early detection is vital, as it enables complete surgical removal, which is usually curative and essential for a good prognosis.3 The aim of this case report is to underscore the critical importance of timely detection and management of diaphragmatic paraganglioma due to its potential for adverse outcomes such as a catecholamine crisis, malignant transformation or metastasis.\n\n\nCase report\n\nA 59-year-old female presented with a significant, unexplained weight loss of 25 pounds over the past four months. During this period, she also experienced symptoms including tremors, flushing, diaphoresis, and palpitations.\n\nA computed tomography (CT) scan of the abdomen revealed a large, heterogeneous solid mass in the right lobe of the liver (Figure 1). Subsequent PET/CT imaging indicated mild activity in the hepatic mass (Figure 2). Laboratory evaluations demonstrated markedly elevated levels of urinary metanephrines, with total metanephrines measured at 10,211 mcg/24 hours (urinary metanephrines at 3,375 mcg/24 hours and urinary normetanephrine at 6,836 mcg/24 hours). Additionally, her blood norepinephrine level was found to be 702 pg/ml. During the surgery, a diaphragmatic paraganglioma was discovered and subsequently resected (Figure 3).\n\n\nDiscussion\n\nParagangliomas and pheochromocytomas share similar cellular characteristics. These tumors occur at a rate of 2 to 8 per million people, with a prevalence of 1 in 2500 to 1 in 6500 individuals.4 Most of these neuroendocrine tumors are pheochromocytomas, while the rest are paragangliomas.\n\nParagangliomas are rare neuroendocrine tumors originating from extra-adrenal autonomic paraganglia, which are small organs mainly composed of neuroendocrine cells capable of secreting catecholamines. Sympathetic paragangliomas, usually found in the sympathetic paravertebral ganglia of the thorax, abdomen, and pelvis, often produce catecholamines. In contrast, parasympathetic paragangliomas, typically nonfunctional, are located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull.5\n\nApproximately 70-80% of paragangliomas develop from infradiaphragmatic sympathetic ganglia, most frequently originating from the Zuckerkandl organ near the inferior mesenteric artery at the aortic bifurcation. They are less commonly found in the retroperitoneal area around the kidneys and adrenal glands, as well as in the bladder. About 10% of paragangliomas are located in the mediastinal and pericardial areas of the thorax, and close to 20% are found in the head and neck region.6,7 In contrast, only two cases of primary diaphragmatic paragangliomas have been documented in the literature, highlighting their rarity.\n\nWe reported a rare case involving a patient who experienced unexplained weight loss along with other symptoms such as tremors and diaphoresis. Upon further examination, we identified an exceptionally rare primary diaphragmatic paraganglioma. Compared to other paragangliomas, this type is extremely scarce and poses significant challenges in terms of diagnosis and treatment, especially due to the increased risk of complications.\n\nParticularly, the most frequent indicator of excess catecholamines is hypertension, which can occur in continuous or intermittent, often paroxysmal, episodes. These episodes typically come with the classic symptoms of headache, palpitations, and excessive sweating. When all three symptoms occur together, a healthcare provider can diagnose a catecholamine-secreting tumor with 90% specificity. However, the chance of these symptoms appearing simultaneously is around 40% and is highly unlikely, as was the case with our patient, who did not show any signs of hypertension.5\n\nMost paragangliomas are found by chance or because of the mass effect they cause. Additionally, 27% of incidental paragangliomas required pathological examination of the removed tissue to confirm the diagnosis.8 In this case, it was challenging to determine whether the tumor was located in the diaphragm or the liver. The difficulty in diagnosis was compounded by the fact that the diaphragm is an extremely rare location for a paraganglioma, making the differential diagnosis particularly challenging.\n\nThe first step in diagnosing a paraganglioma is to assess the patient for elevated levels of catecholamines, followed by identifying the tumor anatomically. This evaluation usually starts with measuring urinary or plasma fractionated metanephrines, as these are formed from catecholamines within the tumor, regardless of the tumor’s catecholamine secretion.9 After confirming catecholamine excess, imaging tests such as magnetic resonance imaging (MRI), or contrast-enhanced computed tomography of the abdomen and pelvis are preferred (nonionic contrast is needed for CT to avoid a catecholamine crisis).10 Given the risk of massive hemorrhage from a biopsy due to the tumor’s hypervascularity, radiologic diagnosis is generally preferred.11\n\nDistinctly, some functioning paragangliomas may not exhibit symptoms at rest, but direct interventions such as surgery can provoke rapid blood pressure changes. Additionally, manipulation during surgery can stimulate the tumor to release more catecholamines, potentially leading to complications such as hypertension, arrhythmias, or severe bleeding. Reports indicate that the surgical mortality rate for paragangliomas due to these issues can be as high as 5.5%. Therefore, like in our case, even if a patient shows no apparent symptoms like high blood pressure or headaches, preoperative catecholamine levels should still be assessed.12 Preoperative clinical therapy, lasting between 7 and 30 days, is essential to prevent intraoperative hypertensive crises, cardiac arrhythmias, and post-surgery hypotension, with recommendations emphasizing the use of alpha-adrenoceptor blockers.13\n\nCharacteristically, in situations where there isn’t a strong suspicion of a paraganglioma, proceeding with manipulation of the mass without proper preoperative pharmacologic blockade poses significant risks, as the condition may go undetected. If there is even a slight suspicion of a paraganglioma, preoperative pharmacologic blockade should be implemented, as the benefits generally outweigh the risks. Attempted resection of most hypervascular masses should be postponed until more detailed biochemical and radiographic information is available.14\n\nComplete surgical resection is considered the preferred treatment for pheochromocytomas and paragangliomas. Laparoscopic surgery is increasingly becoming the preferred method for adrenal tumor resection, as it reduces postoperative morbidity, hospital stays, and costs compared to the traditional transabdominal approach, and also minimizes adhesion formation.15 However, laparoscopic resection of paragangliomas is less commonly used due to concerns about a higher risk of malignancy (though most paragangliomas are benign, metastatic disease can occur in 35-40% of cases) and the fact that paragangliomas are often located near major vascular structures such as the inferior vena cava and aorta,16 which adds to the surgical complexity, as seen in this patient.\n\n\nConsent\n\nA written informed consent was obtained from the patient for the publication of this case report.",
"appendix": "Data availability\n\nNo data associated with this article.\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nAcknowledgements\n\nNone.\n\n\nReferences\n\nMinegishi K, Tsubochi H, Ohno K, et al.: Diaphragmatic paraganglioma protruding into the right thoracic cavity. Thorac Cancer. 2021 Apr; 12(7): 1115–1117. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAygun N, Uludag M: Pheochromocytoma and Paraganglioma: From Epidemiology to Clinical Findings. Sisli Etfal Hastan. Tip Bul. 2020 Jun 3; 54(2): 159–168. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAyala-Ramirez M, Feng L, Johnson MM, et al.: Clinical risk factors for malignancy and overall survival in patients with pheochromocytomas and sympathetic paragangliomas: primary tumor size and primary tumor location as prognostic indicators. J. Clin. Endocrinol. Metab. 2011 Mar; 96(3): 717–725. PubMed Abstract | Publisher Full Text\n\nKiernan CM, Solórzano CC: Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, and Treatment. Surg. Oncol. Clin. N. Am. 2016 Jan; 25(1): 119–138. PubMed Abstract | Publisher Full Text\n\nNeumann HPH, Young WF Jr, Eng C: Pheochromocytoma and Paraganglioma. N. Engl. J. Med. 2019 Aug 8; 381(6): 552–565. PubMed Abstract | Publisher Full Text\n\nPatel D, Phay JE, Yen TWF, et al.: Update on Pheochromocytoma and Paraganglioma from the SSO Endocrine/Head and Neck Disease-Site Work Group. Part 1 of 2: Advances in Pathogenesis and Diagnosis of Pheochromocytoma and Paraganglioma. Ann. Surg. Oncol. 2020 May; 27(5): 1329–1337. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLam AK: Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours. Endocr. Pathol. 2017 Sep; 28(3): 213–227. PubMed Abstract | Publisher Full Text\n\nErickson D, Kudva YC, Ebersold MJ, et al.: Benign paragangliomas: clinical presentation and treatment outcomes in 236 patients. J. Clin. Endocrinol. Metab. 2001 Nov; 86(11): 5210–5216. PubMed Abstract | Publisher Full Text\n\nCanu L, Van Hemert JAW, Kerstens MN, et al.: CT Characteristics of Pheochromocytoma: Relevance for the Evaluation of Adrenal Incidentaloma. J. Clin. Endocrinol. Metab. 2019 Feb 1; 104(2): 312–318. PubMed Abstract | Publisher Full Text\n\nIkram A, Rehman A: Paraganglioma. [Updated 2024 Feb 29]. StatPearls. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Reference Source\n\nMatsumoto J, Nakajima J, Takeuchi E, et al.: Successful perioperative management of a middle mediastinal paraganglioma. J. Thorac. Cardiovasc. Surg. 2006 Sep; 132(3): 705–706. PubMed Abstract | Publisher Full Text\n\nKittaka H, Yamada T, Gotoh K, et al.: A report of case of paraganglioma originated from the diaphragm. Jpn. J. Gastroenterol. Surg. 2012; 45(5): 559–565. Publisher Full Text\n\nJúnior LJV, Kater CE: The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management. Int. Braz. J. Urol. 2023 May-Jun; 49(3): 307–319. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartinez JD, Zendejas B, Luna JP, et al.: Left subdiaphragmatic paraganglioma supplied by contralateral right renal artery. Int. J. Surg. Case Rep. 2012; 3(7): 333–337. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGutt CN, Oniu T, Schemmer P, et al.: Fewer adhesions induced by laparoscopic surgery? Surg. Endosc. 2004 Jun; 18(6): 898–906. Epub 2004 Apr 27. PubMed Abstract | Publisher Full Text\n\nMitchell J, Siperstein A, Milas M, et al.: Laparoscopic resection of abdominal paragangliomas. Surg. Laparosc. Endosc. Percutan. Tech. 2011 Feb; 21(1): e48–e53. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "328600",
"date": "10 Oct 2024",
"name": "Julia Meade",
"expertise": [
"Reviewer Expertise cancer predisposition syndromes",
"pediatric & AYA endocrine tumors."
],
"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 documents the discovery of a diaphragmatic paraganglioma masquerading as a liver tumor. It highlights the importance of expanding one's differential diagnosis to catecholamine-secreting tumors in the abdomen and thinking beyond standard liver cancer diagnoses. 1) please include details to help readers understand the differential diagnosis of the mass, and what prompted you to order metanephrines. 2) please describe if alpha-blockade was used prior to surgery. 3) add normal reference ranges for your labs 4) The case report requires more details - did the tremors/flushing/diaphoresis/palpitations prompt the ordering of metanephrines? # what is the timeline for evaluation, did all this happen in a relatively short period of time, or was there a step-by-step approach to understanding the diagnosis? 5) Figure 3 - please mention that it is liver segment VII and VIII. 6) In the case report - please mention how the patient recovered post-operatively and if they are alive and doing well since the intervention. 7) As you mention a previously published case of a diaphragmatic paraganglioma (reference 12), consider discussing the novel features or lessons from your case. What new information are you adding beyond what Kittaka et al already published?\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": [
{
"c_id": "12660",
"date": "25 Oct 2024",
"name": "Ermilo Echeverria Ortegon",
"role": "Author Response",
"response": "Thank you so much for the feedback. I already addressed this questions in the new uploaded document. I am aware of any changes and requests for modifications. Regards."
}
]
},
{
"id": "328595",
"date": "10 Oct 2024",
"name": "Amjad Kanj",
"expertise": [
"Reviewer Expertise Pulmonary Infections",
"NTM lung disease",
"Bronchiectasis",
"Mediastinal mass"
],
"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 of diaphragmatic paraganglioma provides valuable teaching points about the diagnosis and management of this rare condition. The authors offer insightful radiology images and detailed intraoperative photographs. However, few aspects of the case require clarification.\nThe sequence of events in this case is not entirely clear. The patient presents with unintentional weight loss and symptoms of sympathetic hyperactivity. The authors mention obtaining an abdominal CT scan right of the bat, although this imaging modality would not typically be part of the initial diagnostic workup for such symptoms. A PET-CT scan was performed afterward, but it is unclear whether specific imaging findings prompted biochemical testing for paraganglioma thereafter or if this was based solely on the clinical presentation. It is also unclear if the lesion was biopsied before surgery and whether the patient received adequate alpha- and/or beta-adrenergic blockade.\nSeveral important questions need to be explicitly addressed in the text:\nWere the symptoms of catecholamine excess episodic? If so, how frequent were they? Why was the abdominal CT scan obtained? Was IV contrast used? Describe the imaging findings in more details…. Was the CT performed before metanephrines were measured? What prompted you to check urinary and blood catecholamines? Symptoms only or symptoms +images or…? Did the patient receive alpha or beta blockade before surgery? Do you have pathology images or, at the very least, a description to share? Did the patient have any surgical complications? How was recovery? Did the patient have any personal or family history of paraganglioma, and was genetic testing performed?\nLastly, the authors mention that there are only two other similar cases in the literature. These are few other similar cases such: Buckley K, et al, 1995 [Ref-1], Minegishi K, et al., 2021 [Ref-2], Campo-Rivera N, et al., 2021 [Ref-3], Wu X,et al., 2020 [Ref-4], Martinez J, et al., 2012 [Ref-5], and the report from Minegishi K, et al., 2021 [Ref-2] also mentions there were two other cases.\nAddressing these points will significantly improve the clarity and educational value of the case.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": [
{
"c_id": "12661",
"date": "25 Oct 2024",
"name": "Ermilo Echeverria Ortegon",
"role": "Author Response",
"response": "Thank you so much for the feedback. I already addressed the concerns in the new document. Unfortunately I could not get a hold of the pathology images or description. I'll be glad to make any new modifications or address more questions. Regards."
}
]
}
] | 1
|
https://f1000research.com/articles/13-1023
|
https://f1000research.com/articles/13-616/v1
|
11 Jun 24
|
{
"type": "Systematic Review",
"title": "Current real world health data of telemedicine for heart failure with reduced ejection fraction: a systematic review and meta-analysis",
"authors": [
"Yohanes William",
"Tinanda Tarigan",
"Jery Chen",
"Muhamad Taufik Ismail",
"Hariadi Hariawan",
"Yohanes William",
"Tinanda Tarigan",
"Jery Chen",
"Hariadi Hariawan"
],
"abstract": "Abstract*\nBackground Telemedicine has improved adherence to heart failure (HF) treatment, however it has not yet been tailored specifically to address HF with reduced ejection fraction (HFrEF). Our objective is to undertake a comprehensive systematic review and meta-analysis of existing research studies that focus on telemedicine in HFrEF.\n\nMethods We conducted an extensive literature review encompassing trials which included outpatients with HFrEF who underwent telemedicine compared with usual care. We exclude any studies without ejection fraction data. Three bibliographic databases from PubMed, ScienceDirect, and Cochrane Library were utilized in our search from January 1999 to May 2023. The endpoints of interest included all-cause mortality, cardiovascular-related mortality, all-cause hospitalization, and HF-related hospitalization. The Cochrane risk-of-bias (RoB) and the risk of bias in non-randomized studies – of interventions (ROBINS-I) were used for non-randomized or observational studies. To quantitatively analyze the collective findings, a pooled odds ratio (OR) was computed for each outcome.\n\nResults Out of the initial pool of 4,947 articles, we narrowed down our analysis to 27 studies, Results showed that telemedicine significantly reduced all-cause mortality (OR: 0.65; 95% CI 0.54 – 0.78; p<0.00001), cardiovascular-related mortality (OR 0.68, 95% CI 0.58 – 0.80, p < 0.00001), and HF-related hospitalization based on number of events (OR 0.77, 95% CI 0.64 – 0.94, p = 0.009) as well as number of patients (OR 0.78, 95% CI 0.69 – 0.87, p < 0.0001).\n\nConclusion Telemedicine was shown significantly beneficial in decreasing mortality and hospitalization in HFrEF patients. Future research should focus on standardizing effective telemedicine practices due to the existing variability in methods and clinical situation of the patients. PROSPERO: CRD42023471222 registerd on October 21, 2023",
"keywords": [
"telemedicine",
"heart failure",
"reduced ejection fraction",
"mortality",
"hospitalization"
],
"content": "Introduction\n\nHF has been known for its major public health concern with substantial morbidity and mortality. Its 1-year mortality rate is 7.2% and 31.9% of 1-year hospitalization rate.1 In the US, approximately 1 million hospitalizations of HF, are caused by HFrEF.2 The OPTIMIZE-HF study enrolling 20,118 patients with HFrEF, reported a higher in-hospital mortality in HFrEF (3.9%) than in HF with preserved ejection fractions (HFpEF) patients (2.9%).3 In a prospective longitudinal study conducted in multiple centers in New Zealand and Singapore, 17% of patients (343 individuals) died during the two-year follow-up period. After accounting for factors such as age, sex, and clinical risk factors, it was observed that patients with HFpEF had a reduced risk of death in comparison to those with HFrEF (HR 0.62, 95% CI 0.46–0.85, p = 0.003).4 In a cohort of 4880 individuals from China, a 5-year follow-up until the end of December 2019 revealed a decrease in ejection fraction category was identified as an independent factor associated with an elevated 5-year mortality risk. Specifically, individuals with HFrEF had a mortality rate of 25.2%, while those with HFpEF exhibited a lower rate at 13.4% (adjusted hazard ratio (aHR) 1.85, CI 95% 1.45-2.35, p <0.001).5\n\nDespite the proven efficacy of guideline-directed medical therapy (GDMT) in reducing morbidity and mortality, a significant number of eligible patients diagnosed with HFrEF do not receive one or more of the recommended medications. This shortfall is frequently attributed to suboptimal initiation and titration practices in the outpatient setting. After discharge, the continuation of progress and the safety of initiating and adjusting GDMT in the hospital relies on the successful transition of care to the outpatient setting.6\n\nThe COVID-19 pandemic had brought about a positive outcome in the form of the widespread adoption of telemedicine. This approach, involving the remote delivery of optimal diagnostic and therapeutic services, has proven particularly beneficial for patients with HF during the pandemic. The effectiveness of telemedicine is enhanced through intensive monitoring and more frequent transmission of patient data. This not only improves patient outcomes but also minimizes the risk of virus exposure for healthcare workers.7 The challenge of achieving GDMT can be alleviated by incorporating telemedicine which has proven some beneficial effects. A systematic review conducted by Yun et al. revealed a 19% reduction in all-cause mortality through telemedicine.8 Specifically, several studies have confirmed the enduring benefits of telemedicine for individuals with HFrEF, particularly in terms of reducing mortality and hospitalization rates. A RCT conducted over a 120-month period demonstrated a significant and prolonged decrease in all-cause mortality, underscoring the lasting positive effects of telemedicine.9 In the most recent systematic review and meta-analysis by Scholte et al., a noteworthy 16% decrease in all-cause mortality was observed. Additionally, there were significant reductions of 19% in first HF hospitalization and 15% in total HF hospitalization.10 It is important to note, however, that none of these studies distinguished HF based on ejection fraction.\n\nWe aim to dig deeper to answer the question of whether it is truly beneficial for patients with reduced ejection fraction, who clearly show higher frailty with a higher risk of adverse clinical outcomes.11\n\n\nMethods\n\nWe conducted an extensive and systematic literature review based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassing trials spanning from January 1999 to May 2023.12 Three bibliographic databases from PubMed, ScienceDirect, and Cochrane Library were utilized in our search. Our study was registered in PROSPERO: CRD42023471222 on October 21, 2023. The search terms were “heart failure”, “HF”, “reduced”, “ejection fraction”, “HFrEF”, “telemonitoring”, “telemedicine”, “telemedical”, “telecardiology”. The PRISMA flow diagram is displayed in Figure 1 in data availability section.\n\nThe inclusion criteria are trials/studies which include HFrEF patients or studies with mentioned ejection fraction of ≤40%, with consistent outcome of all-cause mortality, cardiovascular-related mortality, all-cause hospitalization, or HF-related hospitalization. We included any form of telemedicine or telemonitoring such as home telemonitoring (HTM) or telephone support (TS). Any forms of abstracts without full-text articles, case reports, expert opinions, conference presentations, preclinical studies, or whether the articles were not available in English, were excluded from our study.\n\nAll articles retrieved through the systematic search underwent initial screening of their titles and abstracts by two authors and were subsequently grouped into a single folder. The same authors then conducted a thorough examination of the full texts to determine whether the articles met the eligibility criteria or not.\n\nWe included all-cause mortality as our primary outcome, where HF-related mortality, all-cause hospitalization, and HF-related hospitalization as our secondary outcomes. All-cause hospitalization and HF-related hospitalization were both extracted based on number of events (per patient-year) and number of patients. Patient-year was calculated as follows: the total number of patients who participated in the study is multiplied by the total years of follow-up. Studies involving more than two telemedicine interventions were divided into separate studies within the forest plot and meta-analysis. In the table outlining baseline characteristics, we incorporated information on NYHA classification, ejection fraction, follow-up duration in months, study design, participant age, monitoring methods, telemedicine types, and usual care modalities. These data were extracted from the supplementary tables and figures provided in the articles. Two independent investigators each collected the data from the retrieved article. In cases where data interpretation was inconclusive, we sought the input of our third author and reached a consensus. Articles that satisfied the eligibility criteria but lacked the raw data necessary for meta-analysis were excluded from the study. Table 1 presents the fundamental feature of each study, while Table 2 provides a summary of the results and subgroup analysis.\n\n* =studies included in this analysis were less than 3 studies; CI=confidence interval; HF=heart failure; I2=heterogeneity; NA=not applicable; OR=odds ratio.\n\nWe employed Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) as the recommended tool for evaluating the risk of bias in randomized trials. Two authors independently evaluated the articles for risk-of-bias, and if any author encountered confusion, a third author was consulted to establish a consensus.\n\nWe employed a forest plot to effectively present the outcomes of our primary endpoints. Specifically, we will use forest plots for binary endpoints, accompanied by 95% confidence intervals (CI). To assess heterogeneity among the studies, we will utilize the I2 statistic. I2 values ranging from 0% to 25% will be labeled as “low,” 25% to 50% as “moderate,” and >50% as “high”.13 Subgroup analysis of non-invasive and invasive group was conducted to explore possible causes of heterogeneity. Any p-values below 0.05 will be considered statistically significant. All statistical analyses will be carried out using Review Manager (RevMan). The odds ratio was calculated to evaluate the risk of mortality and hospitalization in the available studies. Mortality was calculated based on the total number of patients, while hospitalization was calculated based on the numbef of events of total patient-year and number of patients. Sensitivity analyses were carried out based on different follow-up durations (< 6 months, 6-11 months, and ≥ 12 months) to assess the strength of the study results.\n\n\nResults\n\nWe conducted an extensive literature review encompassing trials spanning from 1999 to the present. Out of the initial pool of 4,947 articles, we narrowed down our analysis to 53 studies, in which our two main authors each reviewed the full-text articles. We excluded 16 articles because of the numerous reasons mentioned in our PRISMA figure (Figure 1). Finally, 27 studies were included in qualitative and quantitative synthesis. Among all of the studies which compared usual care and telemedicine, we found 24 articles reported all-cause mortality and 14 articles reported cardiovascular-related mortality. For all-cause hospitalization, there are 5 studies which reported all-cause hospitalization based on number of events while 13 studies reported with total number of patients. In HF-related hospitalization, 8 studies reported HF-related hospitalization based on number of events, and 16 studies reported with total number of patients. We also conducted subgroup analysis of non-invasive and invasive approach, as well as sensitivity analyses with the aim of attaining a lower level of heterogeneity. Table 2 provides a summary of the included studies and the outcomes associated with subgroup analyses (non-invasive and invasive approache) as well as the sensitivity analyses (Table 2).\n\nWe evaluated the quality of our 24 RCT studies using the Cochrane RoB 2 tool (Figure 2), while the 3 observational studies were assessed using the ROBINS-I tool (Figure 3). For RCT studies, the overall bias with the RoB 2 tool was distributed as follows: 37.5% at low risk, 50% with some concerns, and 12.5% at high risk (Figure 4). High-risk studies were primarily attributed to poorly described randomization processes. The overall quality of the observational studies by ROBINS-I tool was assessed as moderate risk, primarily within domain 1 bias (bias due to confounding). This was because the studies did not explicitly mention confounding factors or adjustments made for them.\n\nThe general characteristics of the population, type of interventions and control group were included in Table 1 along with the primary and secondary outcomes. The lowest time of follow-up was 1.5 months and the longest time of follow-up was 120 months.9,14 Of the 27 studies included, there are 3 studies which were not randomized.15–17 8 studies used implanted devices either it is implantable-cardiac-device (ICD) or cardiac-resynchronization-therapy device (CRT-D).15,18–24 The other 19 studies used non-invasive devices.9,14,16,17,25–39 While most of the usual care/control groups were categorized for in-clinic follow-up only, there were 3 studies which allowed for the patients in the control group to occasionally contact their physician/nurse.25,31,33 All of the noninvasive interventions monitored the patients using standard telephone/telemonitored/telehealth features interactively. Most reported outcomes included all-cause mortality, cardiovascular-related mortality, all-cause hospitalization, and HF-related hospitalization.\n\nTwenty-four studies reported all-cause mortality, involving a total of 9,737 participants, while 14 studies presented data on cardiovascular-related mortality, involving a total of 7,477 participants (studies with more than 2 intervention arms were divided). The meta-analysis revealed a noteworthy decrease in the risk of all-cause mortality (OR 0.65, 95% CI 0.54 – 0.78, p < 0.00001, I2 = 41%) (Figure 5) and a significant reduction in the risk of cardiovascular-related mortality (OR 0.68, 95% CI 0.58 – 0.80, p < 0.00001, I2 = 7%) (Figure 6).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\nIn two analyses focusing on all-cause hospitalization, one based on number of events and the other on the number of patients admitted. Findings from 5 studies totaling 7,302 patient-years reported incidents of hospitalization based on number of events (Figure 7; Figure 8). However, these results did not show a significant reduction in the risk of all-cause hospitalization based on number of events (OR 0.73, 95% CI 0.54 – 1.00, p = 0.05, I2 = 78%) (Figure 7). Thirteen studies with total participants of 5,731 mentioned studies of number of patients who went for admission for all-cause, also with insignificant reduction of the risk (OR 0.85, 95% CI 0.69 – 1.03, p = 0.10, I2 = 66%) (Figure 8). Eight studies with total patient-year of 9874 reported HF-related hospitalization based on number of events with no significant reduction of the risk (OR 0.77, 95% CI 0.64 – 0.94, p = 0.009, I2 = 61%) (Figure 9). Sixteen studies with total number of patients 7478, reported HF-related hospitalization based on total number of patients who went for admission, with significant reduction of the risk (OR 0.78, 95% CI 0.69 – 0.87, p < 0.0001, I2 = 0%) (Figure 10).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\n(HTM=home telemonitoring; TS=telephone support).\n\nWe performed a subgroup analysis comparing non-invasive and invasive approaches in terms of all-cause mortality. The non-invasive approach showed a significantly lower result (OR 0.69, 95% CI 0.59 – 0.80, p < 0.00001, I2 = 0%), whereas the invasive approach did not yield a significant result (OR 0.70, 95% CI 0.42 – 1.15, p = 0.16, I2 = 73%) (Figure 11). In the non-invasive subgroup analysis of cardiovascular-related mortality, a lower significant outcome was observed (OR 0.69, 95% CI 0.58 – 0.82, p = 0.0001, I2 = 0%), while the invasive approach showed a similar outcome with no significant result (OR 0.63, 95% CI 0.36 – 1.08, p = 0.09, I2 = 51%) (Figure 12). The sensitivity analyses of the all-cause mortality in non-invasive group achieved significant result, similar with the main analysis (see Extended data section for supplementary figures1-6). We were not able to conduct the same sensitivity analysis in the invasive group due to the lack of number of the studies.\n\nWe also conducted subgroup analyses for both non-invasive and invasive approaches, focusing on all-cause hospitalization events and the number of patients experiencing all-cause hospitalization and HF-related hospitalization. The non-invasive subgroup analysis of all-cause hospitalization based on the number of events yielded a significant result, albeit with high heterogeneity (OR 0.68, 95% CI 0.48 – 0.94, p = 0.02, I2 = 79%) (Figure 13), while the non-invasive subgroup analysis of all-caused hospitalization based on the number of patients did not have any significant result (OR 0.83, 95% CI 0.66 – 1.04, p = 0.11, I2 = 68%) (Figure 14). The non-invasive subgroup analysis of HF-related hospitalization based on the number of events showed a significant result (OR 0.77, 95% CI 0.62 – 0.95, p = 0.01, I2 = 58%) (Figure 15). Unfortunately, the invasive subgroup analyses of all-cause hospitalization and HF-related hospitalization based on number of events could not be conducted due to a low number of studies. When considering the number of patients, the non-invasive subgroup analysis of HF-related hospitalization demonstrated a significant result (OR 0.77, 95% CI 0.65 – 0.90, p = 0.001, I2 = 15%), and a similar result was observed in the invasive subgroup analysis (OR 0.80, 95% CI 0.65 – 0.97, p = 0.03, I2 = 0%) (Figure 16).\n\nWe attempted to conduct a sensitivity analysis for all-cause hospitalization by the number of patients and for HF-related hospitalization in the non-invasive group. The results indicated significance in studies with a follow-up period of ≥12 months in HF-related hospitalization, similar with the main analysis, but not in the all-cause hospitalization (see extended data: Supplementary figure 9; Supplementary figure 10). There were not enough studies with follow-up periods of < 6 and 6 – 12 months in non-invasive group in both all-cause and HF-related hospitalization, therefore the analyses were considered invalid. We also were not able to conduct the same sensitivity analysis in hospitalization based on number of events in non-invasive group, and in all of the outcomes in the invasive group, due to the same reasoning.\n\n\nDiscussion\n\nAs the emphasis of contemporary healthcare is progressively transitioning from treating illnesses to proactively preventing them and supporting recovery, remote monitoring and telemedicine are poised to become pivotal areas of interest for both scientific research institutions and manufacturers in the coming years.40 The first definition was proposed by the World Health Organization (WHO) in 2007 as follows, “The delivery of health care services, where distance is a critical factor, by all health care professionals using information and communication technologies for the exchange of valid information for diagnosis, treatment and prevention of disease and injuries, research and evaluation, and for the continuing education of health care professionals, all in the interests of advancing the health of individuals and their communities”.41\n\nHF is a common, debilitating, unpredictable, gradually worsening condition with a poor outlook, which places a substantial strain on resources and finances. Objectives in managing HF encompass enhancing symptoms, functional capabilities, quality of life, and patient self-efficacy, while also aiming to lower hospital admissions, mortality rates, and the associated logistical and financial burdens.42 Despite recent pharmacological and therapy advancements, HF, particularly with reduced ejection fraction confers a high morbidity and mortality worldwide.43 The primary objective of remote monitoring for HF is to identify early signs of HF hemodynamic deterioration, enabling timely intervention and thereby preventing HF-related hospitalizations. Therefore, telemedicine might offer more frequent monitoring of patients’ status remotely and could be used as a tool to improve outcomes.41,44\n\nOur meta-analysis, which comprises 27 studies focused on telemedicine in HFrEF suggests that telemedicine system significantly reduced all-cause mortality and cardiovascular-related mortality, in either main analysis, subgroup analyses, and sensitivity analyses. Our analysis also showed significant result in HF-related hospitalization in the main analysis. Previous meta-analysis of RCTs which included 29 RCTs showed that telemedicine significantly reduced all-cause hospital admission (OR 0.82, 95% CI 0.73-0.91, p <0.00001) and cardiac hospital admission (OR 0.83, 95% CI 0.72-0.95, p =0.003).44 Different from the meta-analysis of Zhu et al., we included both RCT and Non-RCT studies and specifically assessed HFrEF patients. Telemedicine via remote telemedicine (RTM) offers patients a structured approach to managing their health conditions and can empower them to take control of their well-being. The primary focus of telemedicine is the timely identification of deteriorating health conditions and the swift implementation of medical interventions.45\n\nThe management of HFrEF has advanced throughout the years.46 Despite well-established evidences and guidelines regarding GDMT, its implementation is still poor in clinical practice.47,48 The major challenges are concern of side effects and inadequate patients’ follow up. Close-monitoring of vital signs, weight and patients’ symptoms, are important to guide dose titration of GDMT medications, which may be difficult to obtain during daily out-patient visits, including for patients with HFrEF. Therefore, telemedicine strategy could become useful in tackling this obstacle.45 A pilot study of DAVID-HF trial by Wong et al (2022) showed that daily ambulatory remote monitoring system using arm-band monitor may be feasible for drug dose escalation in HFrEF.49 Other meta-analyses also have indicated that telemedical monitoring for chronic HF can lead to a decrease in overall mortality over a 6 to 12-month follow-up period.50,51 Findings from the Trans-European Network-Home-Care Management System (TEN-HMS) Study demonstrated that HF patients who were assigned to telemedicine immediately after being discharged from the hospital for HF experienced lower mortality compared to patients in the usual care group.26,52 These findings align with our sensitivity analysis, revealing significant results for all-cause and cardiovascular-related mortality across different follow-up durations (< 6 months, 6 – 12 months, and ≥ 12 months) (extended data: Supplementary figure 7; Supplementary figure 8). This suggests that telemedicine is beneficial for both short-term and long-term mortality outcomes. In the period preceding active promotion of GDMT, telemedicine emerged as a valuable tool, facilitating continuous assessment of treatment efficacy. This encompassed the monitoring of essential parameters such as body weight, urine output, blood pressure, electrocardiogram (ECG), heart rate, and the potential manifestation of side effects.25\n\nThe IN-TIME trial revealed three potential mechanisms that could enhance clinical outcomes and reduce overall mortality. These include the timely identification of life-threatening tachyarrhythmia, prompt recognition of suboptimal ICD/RCT-D function, and increased awareness among patients regarding the worsening of symptoms.21 A significant majority, around 80%, of patients experiencing HFrEF will exhibit frequent and intricate ventricular arrhythmias. Particularly in cases of HFrEF, these ventricular arrhythmias can adversely impact cardiac hemodynamics, worsening the HF syndrome. The timely identification of these arrhythmias is crucial as it can lead to more favorable clinical outcomes and mortality.53\n\nIn contrast, individual studies of the TIM-HF and the Tele-HF trial did not confer similar significant results and diverged from those of the TEN-HMS study and the pooled analyses.54,55 This variation could be explained by the diverse nature of studies on RTM that include HF patients with different risk profiles, varying durations of follow-up, and variations in RTM methodologies across trials. Furthermore, the meta-analyses and trials which showed significant results primarily encompassed a combination of telephone-based monitoring (with or without personal intervention) and technology-assisted monitoring reliant on information.25,26,52\n\nIn principle, the use of telemedicine is anticipated to reduce hospitalization rates among patients with HFrEF. Nevertheless, the outcomes from several trials have been varied. We uncovered a substantial overall decrease in HF-related hospitalization, but this reduction was not observed in all-cause hospitalization. To further scrutinize and challenge the analysis, we attempted a more detailed examination. Interestingly, the decrease in all-cause hospitalizations only exhibited statistical significance in the non-invasive group when considering the number of events. On the contrary, HF-related hospitalization consistently demonstrated significant results in the non-invasive group, particularly in sensitivity analyses for the ≥ 12 months group based on the number of patients. Unfortunately, the most of the analysis in the invasive group lacked a sufficient number of studies, but not in the HF-related hospitalization based on number of patients. The most reliably observed trend in terms of hospitalization is the decrease in all-cause hospitalizations based on number of events within the non-invasive group.\n\nGiordano et al. reported a 36% decrease in total hospital readmissions and a 31% decrease in hemodynamic instability, with significantly lower HF hospitalization compared to the usual care group, similar to our main analyses of HF-related hospitalization.30 Conversely, Cleland et al. found no difference in the number of events between the telemedicine and usual care groups.26 The IN-CONTACT trial, which included telemetry, remote + phone, and usual care groups, reported no significant differences in hospitalization rates across all intervention arms.20 These findings align with earlier RCTs, such as the EVOLVO trial. In the EVOLVO trial, a combination of early issue detection through telemedicine and remote management proved more effective in reducing both the duration of hospitalization and mortality, rather than simply decreasing the number of hospitalizations.22 This discrepancy may be attributed to the occurrence of multiple hospitalization events in a single individual as well as low number of studies. Additionally, variations in baseline characteristics of HF patients across studies contribute to the differences, with Giordano et al. including NYHA class IV patients, while the IN-CONTACT trial and EVOLVO trial focused on NYHA class I-III patients, potentially explaining the higher hospitalization rates observed by Giordano et al.20,22,30 In terms of all-cause hospitalization, we could only pinpoint five studies with diverse methodologies and varying risk profiles of patients, all of which considered the number of events as an outcome. This diversity might explain the non-significant results observed in terms of all-cause hospitalization based on number of events (Figure 7).\n\nIn both main analysis and non-invasive all-cause hospitalization based on number of patients, no significant results were attained (Figure 8; extended data: Supplementary figure 9). However, we identified a significant favorable outcome in the sensitivity analysis of HF-related hospitalization based on number of patients, especially in the context of long-term outcomes in non-invasive group (≥ 12 months) (extended data: supplementary figure 10). Our research yielded results consistent with the findings of the Scholte et al. study, showing a significant decrease in hospitalization rates among patients, referred to as first hospitalization or in our study as hospitalization based on number of patients.10 Similar to their study, we observed that most studies demonstrating significant outcomes utilized either complex telemedicine or a combination of structured telephone and HTM. In the study conducted by Giordano et al, they employed a combined strategy, allowing patients to connect with predetermined nurses anytime and anywhere.30 Notably, they reported that the readmission curve did not diverge significantly until at least 100 days, possibly indicating a learning curve among staff in managing patients with telemonitoring. This observation may contribute to the varied prognosis seen in studies with longer follow-up periods. In contrast, we firmly believe, based on the study by Nunes-Ferreira et al., that the core of a successful telemonitoring program lies in the synergy of monitoring and regularly collecting biodata. Additionally, ensuring good patient adherence and compliance emerges as a fundamental key to the success of telemonitoring initiatives.17\n\nCertain observational studies consistently demonstrate a reduction in hospitalization rates, specifically in arrhythmia patients. Piccini et al. conducted such a study and asserted that telemonitoring could alleviate the burden of hospitalization through the early detection of arrhythmia, lead malfunction, or device failure.56 They specifically highlighted the benefits for patients previously diagnosed with atrial fibrillation (AF), noting fewer hospitalizations for stroke, improved adherence to oral anticoagulation, and prompt detection of AF resulting in fewer transient ischemic attacks or strokes.56–58 These results might explain the significant result we had in hospitalizations based on number of events in the non-invasive group, which we further explain in the non-invasive approach section.\n\nNon-invasive home telemonitoring includes HTM, TS, and complex telemonitoring using a combination of TS and/or 24-h call centre.\n\nIn our meta-analysis, we discovered notable benefits associated with a non-invasive approach in terms of all-cause mortality, cardiovascular-related mortality, all-cause and HF hospitalization based on the number of events, as well as HF hospitalization based on the number of patients. The sensitivity analyses also showed similar result with the main analysis (extended data: Supplementary figure 7 – 10). This study is, to our knowledge, the first comprehensive meta-analysis to showcase the advantages of a non-invasive approach for patients with HFrEF. Notably, Scholte et al. demonstrated significant results in reducing all-cause mortality, first hospitalization, and total hospitalizations in patients with HF overall.10 The E-INH trial, the latest study with the longest follow-up period of up to 120 months, yielded similar results with lower all-cause mortality and improved quality of life compared to the usual care group.9 The oldest study included in our meta-analysis, conducted by Gattis et al. in 1999, added that a straightforward evaluation by a clinical pharmacist significantly lowered all-cause mortality and HF events.29 Another study conducted in a rural area with 405 patients by Krum et al. demonstrated a reduction in the composite outcome and the number of patients hospitalized.35\n\nOver the past two decades, even without a standardized protocol, the non-invasive approach has consistently demonstrated significant advantages through simple long-distance follow-up and evaluation. This might be due to, as previously mentioned, patients with HFrEF require improved compliance with GDMT to prevent further deterioration of the ejection fraction. Achieving this outcome necessitates continuous contact with specialists to maintain appropriate medication prescriptions, which might reduce the total number of hospitalizations required for the patients.9 We also believe that the heterogeneity within our non-invasive group is generally low, particularly regarding mortality outcomes, which aligns with findings from a previous meta-analysis by Scholte et al.10 They noted that the low heterogeneity observed in their study was attributed to the inclusion of stable HF patients (NYHA classes I-II). This observation supports the assertion that the non-invasive approach is genuinely advantageous in terms of reducing mortality across various patient profiles.\n\nIn addition to medical therapy, device utilization has become increasingly essential in HF management, particularly HFrEF. Device therapy includes cardiac resynchronization therapy (CRT) and implantation of intracardiac defibrillators, both for the primary and secondary prevention of sudden cardiac death (SCD).59 As HF patients are at increased risk for life-threatening arrhythmias and SCD, ICD should be considered in particular subset of HF patients.60 ICD has been shown to improve outcomes in eligible HF patients, particularly with reduced ejection fraction. It has been endorsed by current European guidelines.43,61 Contemporary ICDs have the capability to continuously assess the functionality of the implanted system, measure clinical parameters, and document the incidence of arrhythmias or other incidents. As a result, they have the potential to offer early alerts regarding alterations in cardiac conditions or safety concerns. All device manufacturers provide remote ICD monitoring technology, allowing physicians to access patient data from a distance and, consequently, minimizing the need for unnecessary routine and interim appointments.61\n\nAt present, studies on the invasive approach to telemonitoring are limited and exhibit diversity. Despite our efforts to perform subgroup and sensitivity analysis focusing on invasive devices, low number of studies, and the lack of standardized methodologies as well as substantial heterogeneity in baseline characteristics among the studies hindered the identification of any meaningful results. The only significant result in the invasive group was the HF-related hospitalizations based on number of patients, with only 4 studies included (Figure 16). Additionally, multiple studies have confirmed the advantages of telemonitoring in invasive devices. The IN-TIME study has yielded promising randomized data that demonstrates the advantages of invasive remote monitoring for implanted devices in improving clinical outcomes. The combined clinical assessment, which considered factors such as overall mortality, HF hospitalizations, changes in the NYHA class, and shifts in patient self-assessment, showed better results in the group utilizing invasive remote monitoring.30 As previously mentioned, Hindricks et al. outlined a potential function of invasive telemonitoring, highlighting its ability to identify suboptimal ICD/RCT-D performance.21 One of the potential harm is that these devices may trigger unnecessary and inappropriate defibrillation shocks, leading to hemodynamic consequences, and associated with excess mortality.62 In this context, telemonitoring can promptly detect such issues and enable early intervention.30 These results align with the TELECART study, where telemonitoring was identified as a predictive factor for hospitalization in HFrEF patients undergoing treatment with invasive devices.23 The RESULTS study similarly supported this finding, revealing that the group with invasive devices exhibited a lower primary endpoint outcome (comprising all-cause mortality or cardiovascular-related hospitalization) and a 50% reduction in in-clinic visits.24 The utilization of invasive techniques is also able to detect imminent deterioration, such as an increase in pulmonary artery pressure.9 While not included in our study, findings from the PREFER study and CONNECT trial suggested that remote monitoring with automatic notifications significantly shortened the time to a clinical decision in response to clinical events, particularly atrial arrhythmias—a prevalent complication in patients with HFrEF.63,64 Scholte et al. reached a similar conclusion with our study, possibly influenced by the limited number of studies included. The analysis indicated that the subgroup analysis focusing on invasive approaches did not reveal significant benefits in terms of mortality and hospitalization.10 Nevertheless, their findings highlighted a specific positive outcome related to IHM, which was associated with a reduction in hospitalizations related to HF by enabling the modification of diuretic dosages to prevent decompensation. This is particularly important, as decompensation stands out as a primary factor contributing to recurrent hospitalizations in HF patients.10 The DOT-HF trial and EVOLVO study also validated this outcome, showing a substantial decrease in HF hospitalizations.22,65 Additional studies on the invasive approach to telemonitoring are necessarily required to validate and confirm the current theory.\n\nTo the best of our knowledge, there are already multiple studies of HF patients with telemedicine/telemonitoring, but our study is one of the first telemedicine studies with HFrEF patients.\n\nThere are a couple of limitations which should be mentioned. Please consider that our meta-analysis identifies substantial concerns related to bias and heterogeneity. This may stem from the considerable diversity and lack of standardization in the interventions studied. Additionally, both subgroup and sensitivity analyses were conducted as part of our efforts to enhance the quality of our analysis. Furthermore, there was a discrepancy in the approaches used among the included studies, with some employing invasive strategies and others non-invasive ones. For instance, in 1999, Gattis et al. employed a clinical pharmacist to evaluate the overall health of patients, which included monitoring vital signs and making adjustments to medications.29 In contrast, the majority of other studies relied on a physician or a combination of a physician and a nurse for these assessments. The criteria for including patients with reduced EF also varied, with most invasive studies involving patients with EF less than 35%, often using ICD or RCT-D. There are also multiple studies which include or exclude chronic stable HF patients (NYHA I-II) or with clinically severe HF (NYHA IV). Additionally, several studies featured more than two intervention arms.20,26,33 The differences in follow-up times were also responsible for the high heterogeneity. We were not able to analyze the differences in subgroup analysis as most of the studies do not always have the preferable outcome of interest.\n\nSubsequently, variations in the definition of “usual care” across these trials may contribute to the absence of a significant reduction in hospitalization. Another factor contributing to the challenge in our meta-analysis is the variation in rehospitalization definitions across multiple articles. Some studies report rehospitalizations based on the total number of events, while others use the total number of patients. The lack of standardized measurements makes it difficult for us to incorporate these diverse data into the meta-analysis.\n\n\nConclusion\n\nIn summary, we underscore that telemedicine has demonstrated its effectiveness in patients with HFrEF. We expect that future researchers will explore invasive approaches further and more on standardizing effective telemedicine practices due to the existing variability in methods and clinical situation of the patients.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nReporting guidelines\n\nFigshare: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Flow-chart (PRISMA) flowchart for “Current real world health data of telemedicine for heart failure with reduced ejection fraction: A systematic review and meta-analysis”. https://doi.org/10.6084/m9.figshare.24995804.v3 66\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\nFigshare: Preferred Reporting Items for Systematic Reviews and Meta-Analyses Flow-chart (PRISMA) checklist for “Current real world health data of telemedicine for heart failure with reduced ejection fraction: A systematic review and meta-analysis”. https://doi.org/10.6084/m9.figshare.24995780.v3 67\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 express their gratitude to Hariadi from the Department of Cardiology and Vascular Medicine, Faculty of Medicine, Public Health, and Nursing at Gadjah Mada University for providing updated insights into systematic review and meta-analysis.\n\n\nReferences\n\nMaggioni AP, Dahlström U, Filippatos G, et al.: EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). 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PubMed Abstract | Publisher Full Text\n\nScholte NTB, Gürgöze MT, Aydin D, et al.: Telemonitoring for heart failure: a meta-analysis. Eur. Heart J. 2023 Aug 14; 44(31): 2911–2926. PubMed Abstract | Publisher Full Text | Free Full Text\n\nReyes EB, Ha JW, Firdaus I, et al.: Heart failure across Asia: Same healthcare burden but differences in organization of care. Int. J. Cardiol. 2016 Nov 15; 223: 163–167. PubMed Abstract | Publisher Full Text\n\nPage MJ, McKenzie JE, Bossuyt PM, et al.: The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29; 372: n71. Publisher Full Text\n\nHiggins JPT, Thompson SG, Deeks JJ, et al.: Measuring inconsistency in meta-analyses. BMJ. 2003 Sep 6; 327(7414): 557–560. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAngermann C, Störk S, Gelbrich G, et al.: Mode of action and effects of standardized collaborative disease management on mortality and morbidity in patients with systolic heart failure: the Interdisciplinary Network for Heart Failure (INH) study. Circ. Heart Fail. 2012; 5(1): 25–35. PubMed Abstract | Publisher Full Text\n\nKurek A, Tajstra M, Gadula-Gacek E, et al.: Impact of Remote Monitoring on Long-Term Prognosis in Heart Failure Patients in a Real-World Cohort: Results From All-Comers COMMIT-HF Trial. J. Cardiovasc. Electrophysiol. 2017 Apr; 28(4): 425–431. PubMed Abstract | Publisher Full Text\n\nMo Y, Chu M, Hu W, et al.: Association between the nurse-led program with mental health status, quality of life, and heart failure rehospitalization in chronic heart failure patients. Medicine (Baltimore). 2021 Mar 12; 100(10): e25052. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNunes-Ferreira A, Agostinho JR, Rigueira J, et al.: Non-invasive telemonitoring improves outcomes in heart failure with reduced ejection fraction: a study in high-risk patients. ESC Heart Failure. 2020 Dec; 7(6): 3996–4004. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBöhm M, Drexler H, Oswald H, et al.: Fluid status telemedicine alerts for heart failure: a randomized controlled trial. Eur. Heart J. 2016 Nov 1; 37(41): 3154–3163. PubMed Abstract | Publisher Full Text\n\nChiu CSL, Timmermans I, Versteeg H, et al.: Effect of remote monitoring on clinical outcomes in European heart failure patients with an implantable cardioverter-defibrillator: secondary results of the REMOTE-CIED randomized trial. Europace. 2022 Feb 2; 24(2): 256–267. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHansen C, Loges C, Seidl K, et al.: INvestigation on Routine Follow-up in CONgestive HearT FAilure Patients with Remotely Monitored Implanted Cardioverter Defibrillators SysTems (InContact). BMC Cardiovasc. Disord. 2018 Jun 28; 18: 131. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHindricks G, Taborsky M, Glikson M, et al.: Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): a randomised controlled trial. Lancet. 2014 Aug 16; 384(9943): 583–590. PubMed Abstract | Publisher Full Text\n\nLandolina M, Perego GB, Lunati M, et al.: Remote monitoring reduces healthcare use and improves quality of care in heart failure patients with implantable defibrillators: the evolution of management strategies of heart failure patients with implantable defibrillators (EVOLVO) study. Circulation. 2012 Jun 19; 125(24): 2985–2992. PubMed Abstract | Publisher Full Text\n\nSardu C, Santamaria M, Rizzo MR, et al.: Telemonitoring in heart failure patients treated by cardiac resynchronisation therapy with defibrillator (CRT-D): the TELECART Study. Int. J. Clin. Pract. 2016 Jul; 70(7): 569–576. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTajstra M, Sokal A, Gadula-Gacek E, et al.: Remote Supervision to Decrease Hospitalization Rate (RESULT) study in patients with implanted cardioverter-defibrillator. Europace. 2020 May 1; 22(5): 769–776. PubMed Abstract | Publisher Full Text\n\nAntonicelli R, Testarmata P, Spazzafumo L, et al.: Impact of telemonitoring at home on the management of elderly patients with congestive heart failure. J. Telemed. Telecare. 2008; 14(6): 300–305. PubMed Abstract | Publisher Full Text\n\nCleland JGF, Louis AA, Rigby AS, et al.: Noninvasive Home Telemonitoring for Patients With Heart Failure at High Risk of Recurrent Admission and Death: The Trans-European Network-Home-Care Management System (TEN-HMS) study. J. Am. Coll. Cardiol. 2005 May 17; 45(10): 1654–1664. PubMed Abstract | Publisher Full Text\n\nDeWalt DA, Malone RM, Bryant ME, et al.: A heart failure self-management program for patients of all literacy levels: A randomized, controlled trial [ISRCTN11535170]. BMC Health Serv. Res. 2006 Dec; 6(1): 30. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDomingues FB, Clausell N, Aliti GB, et al.: Education and Telephone Monitoring by Nurses of Patients with Heart Failure: Randomized Clinical Trial.\n\nGattis W, Hasselblad V, Whellan D, et al.: Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study. Arch. Intern. Med. 1999; 159(16): 1939–1945. PubMed Abstract | Publisher Full Text\n\nGiordano A, Scalvini S, Zanelli E, et al.: Multicenter randomised trial on home-based telemanagement to prevent hospital readmission of patients with chronic heart failure. Int. J. Cardiol. 2009 Jan 9; 131(2): 192–199. PubMed Abstract | Publisher Full Text\n\nGoldberg LR, Piette JD, Walsh MN, et al.: Randomized trial of a daily electronic home monitoring system in patients with advanced heart failure: the Weight Monitoring in Heart Failure (WHARF) trial. Am. Heart J. 2003 Oct; 146(4): 705–712. PubMed Abstract | Publisher Full Text\n\nKöberich S, Lohrmann C, Mittag O, et al.: Effects of a hospital-based education programme on self-care behaviour, care dependency and quality of life in patients with heart failure – a randomised controlled trial. J. Clin. Nurs. 2015 Jun; 24(11–12): 1643–1655. PubMed Abstract | Publisher Full Text\n\nMortara A, Pinna GD, Johnson P, et al.: Home telemonitoring in heart failure patients: the HHH study (Home or Hospital in Heart Failure). Eur. J. Heart Fail. 2009 Mar; 11(3): 312–318. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoehler F, Winkler S, Schieber M, et al.: Impact of remote telemedical management on mortality and hospitalizations in ambulatory patients with chronic heart failure: the telemedical interventional monitoring in heart failure study. Circulation. 2011; 123(17): 1873–1880. PubMed Abstract | Publisher Full Text\n\nKrum H, Forbes A, Yallop J, et al.: Telephone support to rural and remote patients with heart failure: the Chronic Heart Failure Assessment by Telephone (CHAT) study. Cardiovasc. Ther. 2013 Aug; 31(4): 230–237. PubMed Abstract | Publisher Full Text\n\nSoran O, Piña I, Lamas G, et al.: A randomized clinical trial of the clinical effects of enhanced heart failure monitoring using a computer-based telephonic monitoring system in older minorities and women. J. Card. Fail. 2008; 14(9): 711–717. PubMed Abstract | Publisher Full Text\n\nVillani A, Malfatto G, Compare A, et al.: Clinical and psychological telemonitoring and telecare of high risk heart failure patients. J. Telemed. Telecare. 2014; 20(8): 468–475. PubMed Abstract | Publisher Full Text\n\nVoller H, Bindl D, Nagels K, et al.: The First Year of Noninvasive Remote Telemonitoring in Chronic Heart Failure Is not Cost Saving but Improves Quality of Life: the Randomized Controlled CardioBBEAT Trial. Telemed. J. E Health. 2022; 28(11): 1613–1622. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWita M, Orszulak M, Szydło K, et al.: The usefulness of telemedicine devices in patients with severe heart failure with an implanted cardiac resynchronization therapy system during two years of observation. Kardiol. Pol. 2022; 80(1): 41–48. PubMed Abstract | Publisher Full Text\n\nHan X, Chen W, Gao Z, et al.: Effectiveness of telemedicine for cardiovascular disease management: systematic review and meta-analysis. Ann. Palliat. Med. 2021 Dec; 10(12): 12831–12844. Publisher Full Text\n\nTakahashi EA, Schwamm LH, Adeoye OM, et al.: An Overview of Telehealth in the Management of Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2022 Dec 20; 146(25): e558–e568. PubMed Abstract | Publisher Full Text\n\nSilva-Cardoso J, Juanatey JRG, Comin-Colet J, et al.: The Future of Telemedicine in the Management of Heart Failure Patients. Card. Fail. Rev. 2021 Mar; 7: e11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcDonagh TA, Metra M, Adamo M, et al.: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021 Sep 21; 42(36): 3599–3726. Publisher Full Text\n\nZhu Y, Gu X, Xu C: Effectiveness of telemedicine systems for adults with heart failure: a meta-analysis of randomized controlled trials. Heart Fail. Rev. 2020 Mar; 25(2): 231–243. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnker SD, Koehler F, Abraham WT: Telemedicine and remote management of patients with heart failure. Lancet. 2011 Aug 20; 378(9792): 731–739. Publisher Full Text\n\nBozkurt B, Coats AJS, Tsutsui H, et al.: Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur. J. Heart Fail. 2021 Mar; 23(3): 352–380. PubMed Abstract | Publisher Full Text\n\nHaydock PM, Flett AS: Management of heart failure with reduced ejection fraction. Heart. 2022 Sep 12; 108(19): 1571–1579. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRomero E, Yala S, Sellers-Porter C, et al.: Remote monitoring titration clinic to implement guideline-directed therapy for heart failure patients with reduced ejection fraction: a pilot quality-improvement intervention. Front. Cardiovasc. Med. 2023; 10: 1202615. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWong CK, Un KC, Zhou M, et al.: Daily ambulatory remote monitoring system for drug escalation in chronic heart failure with reduced ejection fraction: pilot phase of DAVID-HF study. Eur. Heart J. Digit. Health. 2022 Jun; 3(2): 284–295. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKlersy C, De Silvestri A, Gabutti G, et al.: A Meta-Analysis of Remote Monitoring of Heart Failure Patients. J. Am. Coll. Cardiol. 2009 Oct 27; 54(18): 1683–1694. Publisher Full Text\n\nInglis SC, Clark RA, McAlister FA, et al.: Structured telephone support or telemonitoring programmes for patients with chronic heart failure. Cochrane Database Syst. Rev. 2010 Aug 4; 8: CD007228. Publisher Full Text\n\nKoehler F, Winkler S, Schieber M, et al.: Telemedicine in heart failure: Pre-specified and exploratory subgroup analyses from the TIM-HF trial. Int. J. Cardiol. 2012 Nov 29; 161(3): 143–150. PubMed Abstract | Publisher Full Text\n\nMasarone D, Limongelli G, Rubino M, et al.: Management of Arrhythmias in Heart Failure. J. Cardiovasc. Dev. Dis. 2017 Feb 28; 4(1): 3. Publisher Full Text\n\nChaudhry S, Mattera J, Curtis J, et al.: Telemonitoring in patients with heart failure. N. Engl. J. Med. 2010; 363(24): 2301–2309. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoehler F, Winkler S, Schieber M, et al.: Telemedical Interventional Monitoring in Heart Failure (TIM-HF), a randomized, controlled intervention trial investigating the impact of telemedicine on mortality in ambulatory patients with heart failure: study design. Eur. J. Heart Fail. 2010 Dec; 12(12): 1354–1362. PubMed Abstract | Publisher Full Text\n\nPiccini JP, Mittal S, Snell J, et al.: Impact of remote monitoring on clinical events and associated health care utilization: A nationwide assessment. Heart Rhythm. 2016 Dec; 13(12): 2279–2286. PubMed Abstract | Publisher Full Text\n\nSanna T, Diener HC, Passman RS, et al.: Cryptogenic stroke and underlying atrial fibrillation. N. Engl. J. Med. 2014 Jun 26; 370(26): 2478–2486. Publisher Full Text\n\nMabo P, Victor F, Bazin P, et al.: A randomized trial of long-term remote monitoring of pacemaker recipients (the COMPAS trial). Eur. Heart J. 2012 May; 33(9): 1105–1111. PubMed Abstract | Publisher Full Text | Free Full Text\n\nCabac-Pogorevici I, Muk B, Rustamova Y, et al.: Ischaemic cardiomyopathy. Pathophysiological insights, diagnostic management and the roles of revascularisation and device treatment. Gaps and dilemmas in the era of advanced technology. Eur. J. Heart Fail. 2020 May; 22(5): 789–799. PubMed Abstract | Publisher Full Text\n\nHussein AA, Wilkoff BL: Cardiac Implantable Electronic Device Therapy in Heart Failure. Circ. Res. 2019 May 24; 124(11): 1584–1597. Publisher Full Text\n\nDe Simone A, Leoni L, Luzi M, et al.: Remote monitoring improves outcome after ICD implantation: the clinical efficacy in the management of heart failure (EFFECT) study. Europace. 2015 Aug; 17(8): 1267–1275. PubMed Abstract | Publisher Full Text\n\nKoneru JN, Swerdlow CD, Wood MA, et al.: Minimizing Inappropriate or “Unnecessary” Implantable Cardioverter-Defibrillator Shocks. Circ. Arrhythm. Electrophysiol. 2011 Oct; 4(5): 778–790. Publisher Full Text\n\nCrossley GH, Boyle A, Vitense H, et al.: The CONNECT (Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision) trial: the value of wireless remote monitoring with automatic clinician alerts. J. Am. Coll. Cardiol. 2011 Mar 8; 57(10): 1181–1189. PubMed Abstract | Publisher Full Text\n\nChen J, Wilkoff BL, Choucair W, et al.: Design of the Pacemaker REmote Follow-up Evaluation and Review (PREFER) trial to assess the clinical value of the remote pacemaker interrogation in the management of pacemaker patients. Trials. 2008 Apr 3; 9: 18. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBraunschweig F, Ford I, Conraads V, et al.: Can monitoring of intrathoracic impedance reduce morbidity and mortality in patients with chronic heart failure? Rationale and design of the Diagnostic Outcome Trial in Heart Failure (DOT-HF). Eur. J. Heart Fail. 2008 Sep; 10(9): 907–916. PubMed Abstract | Publisher Full Text\n\nWilliam Y, Tarigan T, Chen J, et al.: Figure 1. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Flow-chart (PRISMA) flowchart for “Current real world health data of telemedicine for heart failure with reduced ejection fraction: A systematic review and meta-analysis”.jpg. figshare. 2024 [cited 2024 Apr 29]. Reference Source\n\nWilliam Y, Tarigan T, Chen J, et al.: PRISMA checklist of “Current real world health data of telemedicine for heart failure with reduced ejection fraction: A systematic review and meta-analysis”.docx. figshare. 2024 [cited 2024 Apr 29]. Reference Source\n\nWilliam Y, Tarigan T, Chen J, et al.: Supplementary figures of “Current real world health data of telemedicine for heart failure with reduced ejection fraction: A systematic review and meta-analysis”. figshare. 2024 [cited 2024 Apr 29]. Reference Source"
}
|
[
{
"id": "310189",
"date": "03 Sep 2024",
"name": "Nisha Nambiar",
"expertise": [
"Reviewer Expertise Public health",
"Biotechnology",
"Biology",
"Plant propagation"
],
"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 general, the authors had produced a good review paper. Researchers fulfilled the minimum requirements in reporting a systematic review and meta-analyses. The rationale and the research objectives were clearly stated in the manuscript. The methods were clearly discussed, allowing readers to replicate the entire process. The data analysis techniques were mentioned clearly by the authors followed by a careful interpretation of the analysis. The systematic review included documents searched from January 1999 to May 2023. It was not clear on the reason why articles from 2024 were not included in the search. Since it is already the 3rd quarter of the year, it would be good if the articles from the year 2024 were included in the data search. Authors are encouraged to include the potential partiality observed while performing this review. In the conclusion, authors should include the summary of the number of articles selected and reviewed followed by the limitations that were observed while performing this review.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Yes\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) No",
"responses": [
{
"c_id": "12465",
"date": "19 Sep 2024",
"name": "Yohanes William",
"role": "Author Response",
"response": "Dear Nisha Nambiar, We are grateful and thank you for your thorough review for our article. Generally, we tried to include the latest articles as many as we could, but we had to decide when we wanted to stop our identification and screening step so we could proceed to the further step. We started our identification step on October 10 2023, and we ended the identification and screening step on November 15 2023. We needed at least 1-2 months for further reviewing process, and we finalized our article at the end of December 2023. We submitted to F1000Research on January 3 2024, and the article was accepted conditionally on May 4 2024. Therefore, we did not include the articles from 2024 in our search. As for the potential partiality, we have included this in the Risk of bias section in the Results. We are at the process adding the summary of this partiality in the conclusion section."
}
]
}
] | 1
|
https://f1000research.com/articles/13-616
|
https://f1000research.com/articles/13-1274/v1
|
24 Oct 24
|
{
"type": "Research Article",
"title": "Hydrodynamic Performance Enhancement of Torpedo-Shaped Underwater Gliders Using Numerical Techniques",
"authors": [
"Sudheendra Prabhu K",
"Srinivas G",
"Sudheendra Prabhu K"
],
"abstract": "Background Underwater gliders are widely used in marine applications for monitoring purposes. These gliders must withstand hydrodynamic forces and maintain its body stability. The underwater environments are highly unpredictable, and small changes in the environment can lead to significant instability in underwater vehicles.\n\nMethods This study uses different numerical techniques to investigate the hydrodynamic characteristics of a torpedo-shaped glider. A symmetric torpedo-shaped glider model was created and analyzed using a licensed version of ANSYS 20.1 Fluent tool. The behavior of the torpedo glider under various flow conditions was examined such as variation of grid test, change of turbulent models, the variation in the inflow boundary conditions involves varying the velocity from 10.16 m/s to 15.16 m/s in 1m/s increment and from 10.16 m/s to 7.66 m/s in 0.5 m/s, also six different models were analyzed.\n\nResults Research was also attempted with different turbulent models and the Spalart-Allmara model was producing least validation error of 1.28 % with a primary focus on nose optimization. By varying the nose length, the study aimed to identify the best-suited nose geometry to minimize drag force. The nose lengths were varied to 0.205 m and 0.19m, resulting in validation errors of 2.81% and 1.16%, respectively, the results are clearly explained in the sub sequent sections of this article.\n\nConclusion In conclusion, this study has evaluated various modifications and their impact on drag force reduction. The application of Spallart-Allmara model resulted in an improvement of 1.28%. Decrease in velocity lead to a significant reduction in the drag force, with an improvement of 37.3%. The nose optimization also contributed to drag force; a nose length of 0.205m yielded a 3.37% improvement. While a 0.19m nose length resulted in a 1.67% reduction. This study helps researchers in hydrodynamics by optimizing geometry for drag reduction.",
"keywords": [
"Torpedo",
"Hydrodynamics",
"CFD",
"Underwater glider",
"Drag."
],
"content": "1. Introduction\n\nThe torpedoes were invented in 1860 by Robert Whitehead, an English engineer in Australia, long before there was a theoretical foundation for the scientific development of underwater missiles. The torpedo is the most destructive naval weapon ever deployed, yet its role in modern warfare is largely ignored by naval professionals, a symmetric geometry of torpedo glider is shown in Figure 1.1\n\nThe analysis of hydrodynamic parameters plays a very important role in underwater torpedo gliders or any underwater vehicles. The hydrodynamic forces are time-varying and very important to maintain the glider’s stability.2 While designing any torpedo glider, various changes arise. Hydrodynamic coefficient parameters need to be considered when designing a glider. In general, gliders travel at very low velocity, with a maximum speed of up to 0.2 m/s to 0.5 m/s.3 Various parameters affect the stability of the torpedo glider, the parameters include lift, drag, mass of the glider, and velocity. These lift, drag, mass, and thrust forces need to be balanced for the stability of the torpedo glider. There are parameters like glider design, Reynolds number, lift-to-drag ratio, and the angle of attack that keep changing during maneuverability, which can vary up to 8°, 9°, or 10°.4–6 The torpedo glider might get unstable due to the internal bouncy system and due to tail-wing geometry.7 A small change in stability leads to a pressure difference, even though the design is correct. Therefore, the glider design needs to be designed in such a way that it can stand up to hydrodynamic forces.8 A few torpedo gliders like Omni-max, Depla, flying wing anchor (FWA), and FISH type anchors are dropped from the air into the water which leads to instability due to changes in the density, instability is also due to the actuating force.9,10\n\n\n2. Literature review\n\nIn underwater it is very difficult to predict stability because of the varying angles of attack. To control drag force is very important for torpedo gliders, these problems are also seen in ships and submarines.11 This can be controlled by changing the torpedo geometry and analyzing using numerical simulations.12 The torpedo nose, tail, and wings are very important parts to control the drag, there are various possible methods to minimize the drag.\n\nThe possible solution includes considering the axisymmetric geometry, avoiding the tail or wing, compered nose, or changing the wing-tail dimensions12,13 and these can be analyzed using computational fluid dynamics (CFD) there various methods for analyzing which include the Datcom method, proper orthogonal decomposition (POD) method, particle image velocimetry (PIV), and fluorescent dye method.14–17 There are also other solutions like changing fin configuration, minimizing the payload, sharp tip angle, high aspect ratio, optimizing the diameter, hemispherical nose, and duct-shaped nose, and super cavitating geometry for the high-speed torpedo.18–21 The study provides the relationship between nose geometry and drag force. In below given subsequent sections, comparison, validation, and the variation in the drag force due to velocity modifications. Similarly, modifications in the nose parabola geometry are clarified; additionally, various numerical methods in the Ansys fluent are performed for comparison, detailed results, and conclusions are provided.\n\nThis research focuses on the aerodynamic performance enhancement of torpedo-shaped underwater vehicles using different numerical techniques. The primary objective of this research article is to test the baseline numerical analysis and validate it with the public literature review. Secondly, the flow conditions are tested with different inlet flow boundary conditions and different turbulence models through the grid independence test, finally identifying the best suitable performance parameters for the chosen torpedo. Finally, the model is also tested for nose shape optimization using the trial-and-error method, identifying the most suitable performance parameters for improved aerodynamic concepts. These objectives provide deeper understanding of the torpedo gliders behavior towards drag force and inform how the design optimization helps in lower drag and better performance in the operating environment.\n\n\n3. Methods\n\nAs per the diagram Figure 2 below, the complete research article identifies the hydrodynamic problems to fulfill the research objective. Initially baseline was done, and the baseline model for the torpedo glider was prepared using ANSYS designs modeler. Later the torpedo glider model was meshed, the analysis was performed, and baseline results were validated by comparing with the article reference 22. Once the baseline analysis was set, the research followed the next step of the objective, which included the Grid independency test to validate the mesh. Further the analysis continued with six different turbulence models, and the Spalart-Allmara vorticity-based model was chosen for the next step because this model was producing least validation error of 1.28%. The drag force due to changes in boundary conditions was analyzed, from this step, the variation in the drag force due to change in velocity is observed. After performing this step, the main aim of the research article is to carry out the nose hydrodynamic shape optimization.\n\nHere the nose of the torpedo glider was increased and decreased to 5 iterations with a step size of 0.05 m. From this step, the variation in the drag was observed, and the best-suited nose geometry to minimize the drag was chosen; the results are discussed in the subsequent sections.\n\n3.1.1 Modelling of torpedo glider\n\nThe torpedo glider is modeled using an ANSYS design modular; the total length of the torpedo is 1.5 m; the nose of the torpedo is a parabola with a length of 0.2 m; the aft length is 0.3 m with 20° tail angle; and the middle body is a cylinder with a diameter of 0.2 m. Similarly, the fluid domain is created, and the dimensions of both the torpedo and fluid domains are shown in Figure 3 and Figure 4, the dimensions of the torpedo glider and the fluid domain were taken from the reference 22.\n\nThe nose body shapes of the torpedo glider model have been optimized through various iterations. These shapes have been plotted using MATLAB with appropriate codes, incrementally increasing and decreasing by 0.05 m, as illustrated in Figure 5.\n\n3.1.2 Meshing of torpedo and fluid domain\n\nAfter creating torpedo model, the torpedo and fluid domain model was imported for meshing, before meshing inflation body was created as shown in Figure 6, acting like additional fluid domain. A general triangular mesh was chosen, with a y+ of 1 and a boundary layer was created around the torpedo surface. In the Figure 7 below, the mesh over the torpedo and fluid domain can be seen. The mesh size chosen for this model was 48.2 mm, and the number of elements was 4.5 million, after multiple iterations this mesh size was chosen as the baseline for the simulation.\n\n3.1.3 Numerical modeling\n\nCFD analysis helps in understanding hydrodynamics on the torpedo gliders or any underwater vehicles, it also helps in understanding the flow behavior of the fluid over the torpedo glider as well as the pressure distribution on the surface of the glider. The speed of the torpedo glider is very small, and the flow is considered as the 3-dimensional steady state and incompressible. The Spallart-Allmaras turbulence model is known as one equation model, describes eddy viscous eddy current flow. This turbulence model is commonly used in aerodynamic applications including wall bounded conditions, since there is only one equation to solve the process is faster compared to other models.\n\nThe governing equation:\n\nThe Spallart-Allmaras model, one equation is given by:\n\nSince the assumption is steady state,\n\nThe turbulent eddy viscosity can be computed from the equation:\n\nWhere ρ is the density, v is molecular kinematic viscosity, and μ is molecular dynamic viscosity. Cb1, Cb2, k and Cv1 are constants. To estimate the lift force (FL) and drag force (FD), the equations (1) and (2) are used.\n\nWhere A is the area on which force is acting. CL and CD are the lift and drag coefficients, and V is the free stream velocity of the fluid, All the above equations from (1) to (7) are referred from Ref. 23.\n\n3.1.4 Boundary conditions on torpedo\n\nAfter meshing the model was taken to ANSYS Fluent and the boundary conditions were applied. The Spalart-allmaras model was chosen for the simulation and the steady state for the torpedo was chosen.\n\nThe velocity was 3.046 m/s, and the angle of attack was 9°, since the torpedo was stationary free stream velocity was calculated and given as 10.16 m/s and the fluid parameters, density of 998 kg/m3 and kinematic viscosity of 1.00481×10− 6 m2/s was set. The torpedo glider was considered as the rigid body, since the speed was too low the far-field was chosen as the wall, and constant density for water was set, the boundary conditions for the Spalart-Allmara vorticity-based model is given in the Table 1.\n\nThe above boundary conditions were set for the baseline for the simulation, Figure 8, Figure 9, and Figure 10 represents the fluent setup including inlet, outlet, wall, and half-plane. The drag force obtained from the above simulation was compared with the experimental study.22 Later stage the velocity was increased from 10.16 m/s to 15.16 m/s and decreased to 7.66 m/s with each increment and decrement step of 1 m/s. At the final stage of the simulation, the nose geometry was altered, and the same boundary conditions were applied. The nose parabola optimization was performed by incrementing and decrementing the parabola length from 0.2 m to 0.22 m during increment and 0.2 m to 0.175 m during decrement. During decrement with 0.05 m step change, the drag force for all the design changes and boundary condition changes can be seen in the result section.\n\n3.1.5 Grid independency test\n\nTo check whether the obtained drag force does not depend on the grid used for the simulation, five different mesh sizes were chosen and resulting in 4.1, 4.2, 4.3, 4.4, and 4.5 million mesh elements in the graph below 4.5 M and 4.4 M are resulting with the same drag force hence the mesh size of 48.2 mm was chosen for the simulation and taken as the base for the analysis of the drag force, the drag force with respect to change in the number cells is observed in Figure 11.\n\n\n4. Results and Discussions\n\nResults were analyzed regarding drag force and the change in the drag force concerning change in the boundary conditions, change in the velocity, and nose optimization for the same (0.2mx1.5m) are discussed. In the below subsection, each step is carried out for analyzing the reports starting from the baseline, method sections, grid independence test, variation of flow velocity, and nose optimization are discussed in detail.\n\nThe baseline boundary conditions are discussed in the methodology section, the velocity of the glider was set to 3.046 and K-omega SST model was applied due vey slower velocity, torpedo glider was assumed to be steady, and the angle of attack was set to 9°. Since the torpedo was considered as wall and free stream velocity of 10.16 m/s from the inlet was set, different mesh sizes were applied for the same SST model. For the mesh size of 48 mm and 48.2 mm the drag force of 86.11 N can be seen in the Table 2, obtained drag forces are compared with the experimental study.22\n\nThe baseline mesh size was set to 48.2 mm, additional 6 different models for the same torpedo glider geometry was tested and from Table 2, the Spalart-Allmara vorticity-based model results in accurate drag force of 86.28 N and this model was chosen for the next analysis seen in Table 3.\n\nFrom the Figure 12 it is observed that the K-kl model results in higher drag force compared to other 5 different models, the k-omega SST model and Sparlart-Allmara Model results in the drag force of 86.11 N and 86.28 N but the aim is to minimize the drag. Therefore, the Sparlart-Allmara Model was chosen for further simulation since the error is less compared to other viscous models.\n\nFrom Figure 13 the velocity of 8.911 m/s is observed that, at the leading edge and flow separation is observed at the trailing edge. Similarly, from Figure 14, an intermediate pressure between 4.78 kPa to 10.67 kPa is observed. The figure also shows that the trailing edge tip has a maximum pressure of 13.61 kPa, both contour and velocity contours can be observed in Figure 13 and Figure 14, utilizing the K-omega SST model.\n\nFrom Figure 15 the velocity of 8.902 m/s is observed at the torpedo leading edge and flow separation at the trailing edge. Similarly, from Figure 16, an intermediate pressure between 1.27 kPa to 10.07 kPa is observed, and the figure also shows that the trailing edge tip has a maximum pressure of 15.94 kPa. The pressure and velocity contours can be observed in Figure 15 and Figure 16 utilizing the Spallart-Allmara vorticity-based model.\n\nIn further validation the velocities are varied from 10.16 m/s and the freestream velocity was incremented and decremented to each of 5 iterations as shown in the Table 4. The velocities are varied to understand the variation the drag force, from the analysis it can be observed that higher the velocity more will be the drag and the angle of attack was set to 9°, the angle of attack also plays very important role in stability as the velocity and angle of attack increases the drag will increases. From the table it is observed that, at 15.16 m/s free stream velocity the drag will be 230.9 N, at 7.66 m/s free stream velocity the drag force will be 54.78 N.\n\nFigure 18 represents the variation in the drag concerning the increment in the velocity by 1m/s and observed that the drag forces increases as the velocity increases, similarly, Figure 17 represents the variation in the drag force due to a decrement in the velocity by 0.5 m/s, from the graph it is observed that the drag force decreases as the velocity decreases.\n\nFigure 18 and Figure 19 represents the velocity and pressure contours at velocity 15.16 m/s, also it is observed that as the velocity increases the pressure on the torpedo glider also increases, this leads to uniform distribution of the fluid streamlines and the change in pressure is also due the angle of attack. As the angle of attack changes with a velocity of the fluid, flow distribution over the torpedo glider changes and as the result there is a pressure difference at the upper and lower part of the geometry. From Figure 18 and Figure 19 it is observed that shape of tails helps in pushing water out more gradually and less abruptly this helps in minimizing the drag. But the sharp nose is not preferred for low-speed gliders.\n\nFrom Figure 19 at velocity of 3.355 m/s it is observed that at the leading-edge surface, maximum velocity of 15.099 m/s, and flow separation at the trailing edge. Similarly, from Figure 20, an intermediate pressure between 1.128 KPa to 20.6 KPa is observed, and the figure also shows that the trailing edge tip has a maximum pressure of 33.59 Kpa. Both pressure and velocity contours can be observed from Figure 19 and Figure 20, utilizing the Spallart-Allmara vorticity-based model. From Figure 22 the velocity of 2.543 m/s is observed at the leading-edge surface, maximum velocity of 7.628 m/s, and flow separation at the trailing edge. Similarly, from Figure 21, an intermediate pressure between 5.79 KPa to 7.027 KPa is observed, and the figure also shows that the trailing edge tip has a maximum pressure of 9.818 KPa, both pressure and velocity contours can be observed from Figure 21 and Figure 22, utilizing the Spallart-Allmara vorticity based model.\n\nFigure 20 and Figure 21 shows the velocity and pressure contour at 7.66 m/s free stream velocity, here the drag force is found to be 54.78 N which is much less compared to 230.9 N drag due to 15.16 m/s free stream velocity. This part of the simulation is just to understand the change in drag due to change in the flow parameters like free stream velocity and angle of attack. Here it can be observed that the drag can be reduced by decreasing the velocity, but the reducing velocity does not help in the torpedo gliders because torpedoes are mainly used for defence applications and they have to maintain a constant speed, as a result, the only way to minimize the drag is by altering the geometry, in the next subsection it is clearly how the drag can be reduced by changing geometry.\n\nIn the defence application, speed is a very important aspect, and the torpedo glider should have minimum speed. Therefore, the speed cannot be reduced to minimize the drag, another alternative method is to modify the geometry. Here nose part is modified because the torpedo travels at a very low velocity compared to missiles hence the tail shape tail part is well suited for this simulation. As the watertight volume changes the drag force will change. This study aims to understand the change in the drag force when the nose is optimized. In this simulation the parabolic nose is considered because the torpedo travels at a very low speed as a result there is no shock wave on the nose surface, since the speed is less parabolic shape can be used, consideration of the parabolic nose is an advantage over the drag but the light of the nose is also very important because as the length changes the total mass and volume also changes which will affect the drag, hence the nose light should be optimum to minimize the drag. in this simulation, the parabolic nose lengths are incremented and decreased as shown in this table and the lengths are changed to 5 iterations with a change in step length of 0.05 m as shown in Figure 5.\n\nFrom Figure 24 as the torpedo length increases from 0.2m the drag force will also increase at each step increment and at 0.215 m nose length the drag force reaches the maximum value of 86.48 N and after further increment the drag force gradually starts decreasing from the graph it is observed that the drag forces decrease from 86.48 N to 85.37 N at the nose length of 0.225 m. Similarly, from Figure 23 the variation in the drag force can be observed, after decreasing the nose length the drag force starts decreasing and from the graph it can be observed that the drag force reaches the minimum value 85.94 N at the nose length of 0.19m, on further decrease in length the drag starts increasing gradually.\n\nIn this simulation the thrust is not considered, here only the change in drag force due to the change in angle of attack is studied. The change in geometry always does not help because if the nose length is reduced then it is not sure that the drag force will increase. After all, the change in overall length is only very important. The length of the torpedo glider is related to total volume whereas the diameter is directly related to total volume, but the fineness ratio and diameter are not related to each other. Hence the fineness ratio can be neglected for this simulation because for that reason the nose optimization is performed, and this study mainly focuses on the design of an symmetric body which will help in reducing the drag force.\n\nThe above figure represents the velocity and pressure contours over the torpedo glider, here the same free stream velocity of 10.16 m/s is considered, and the same boundary conditions are applied. Figure 25 and Figure 26 represent the velocity and pressure contours due to a nose length of 0.205 m. Similarly, Figure 27 and Figure 28 represents the velocity and pressure contours over the torpedo glider at a velocity of 10.16 m/s for the same 0.19 m nose length. The 0.19 m and 0.205 m are chosen because it produces less drag force of 84.54 N and 87.32 N. From Figure 25 the low velocity of 2.224 m/s is observed at the leading-edge surface, maximum velocity of 10 m/s, and flow separation at the trailing edge. Similarly, an intermediate pressure between 2.398 kPa to 5.79 kPa is observed from Figure 26, and the figure also shows that the trailing edge tip has a maximum pressure of 9.818 KPa, both contour and velocity contours can be observed from Figure 25 and Figure 26. Similarly, from Figure 28 an intermediate pressure between 1.157 kPa to 10.01 kPa is observed, and the figure also shows that the trailing edge tip has a maximum pressure of 15.8 kPa, both contour and velocity contours can be observed from Figure 27 and Figure 28.\n\nSeveral numerical methods were employed and analyzed, based on Figure 29 observations. The grid independency test, conducted with a mesh consisting of million elements resulted in a drag force 86.11 N, achieving a 1.47% improvement in drag force reduction. The application of the Spallart-Allmaras model results in a drag force of 86.28 N with a 1.28% improvement in drag force reduction. Further analysis at a velocity of 7.66 m/s demonstrated an improvement in a drag force of 54.78 N, which corresponds to a 37.3% reduction. Additionally, nose optimization was performed, nose length of 0.19 m resulting in a drag force of 85.94 N with 1.67% improvement. Increasing the nose length to 0.205 m further reduced the drag force to 84.54 N, resulting in a 3.27% improvement. These observations highlight the impact of the nose optimization on drag reduction, effectiveness of velocity adjustments and selecting the suitable turbulence model in minimizing the hydrodynamic drag force.\n\n\n5. Conclusions\n\nIn this study, the relationship between the nose geometry of the cylindrical torpedo hull and drag force is investigated using 3D CFD simulation. The study mainly focuses on drag minimization by optimizing the parabolic nose, to optimize the nose many validations are performed. The important step was selecting the proper baseline where the drag force was found to be 86.28 N. The result was validated, there was 1.47% error while comparing with the reference drag force of 87.4 N. After selecting the proper baseline, the torpedo model was simulated for different turbulence models and the Sparlart-Allmara model was chosen as the baseline model for further simulation. In the later stages, the velocities are varied to observe the variation in the drag force, the velocities are incremented from 10.16 m/s to 15.16 m/s where the maximum drag force of 230.9 N is observed. Similarly, the velocity is decreased from 10.16 m/s to 7.16 m/s where a minimum drag force of 54.78 N is observed, from the above steps it can be concluded that the drag force can be minimized by reducing the velocity, but in the defence application speed is always an important parameter. By considering the above aspects nose optimization is chosen where the torpedo glider nose is incremented from 0.2 m to 0.025 m and decrement from 0.2 m to 0.175 m. From this study it can be observed that the 0.205 m and 0.19 m nose lengths produce 84.54 N and 85.94 N drag force which is lower compared to other optimization nose lengths. While comparing with the referenced drag force the error was found to be 3.32% and 1.67% which is acceptable. From the overall simulation it can be observed that the reducing velocity does not reduce the drag, nowadays torpedo speeds are increasing and the possible hydrodynamic solution to reduce the drag force is by optimizing the tail or nose. In this study the focus was to optimize the nose because the speed was less, torpedo glider body was symmetric, and the tail was sharp with the tail angle of 20°. While optimizing the nose it is very important to consider volume and diameter, because the overall length is directly related to total volume and diameter. These design parameters also affect the drag force, hence considering this parameter for the design will help in minimizing the drag force. The future scope of this work includes conducting thermal analysis of the torpedo glider and designing the most suitable geometry. As the torpedo speeds are upgrading, thermal analysis is also essential to predict the drag. Since in the water medium the pressure is much higher compared to an air medium. Therefore, thermal analysis and optimizing the design are crucial to reduce the drag effectively.\n\n\nEthics and consent\n\nEthics and consent were not required.",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nGao T, Wang Y, Pang Y, et al.: Hull shape optimization for autonomous underwater vehicles using CFD. Engineering Applications of Computational Fluid Mechanics. Jan. 2016; 10(1): 599–607. Publisher Full Text\n\nLiu Y, Ma J, Ma N, et al.: Experimental and Numerical Study on Hydrodynamic Performance of an Underwater Glider. Math. Probl. Eng. 2018; 2018: 1–13. Publisher Full Text\n\nYang L, Cao J, Cao J, et al.: Hydrodynamic and vertical motion analysis of an underwater glider. OCEANS 2016 - Shanghai, China. 2016; pp. 1–6. Publisher Full Text\n\nSingh Y, Bhattacharyya SK, Idichandy VG: CFD approach to modelling, hydrodynamic analysis and motion characteristics of a laboratory underwater glider with experimental results. Journal of Ocean Engineering and Science. Jun. 2017; 2(2): 90–119. Publisher Full Text\n\nSingh Y, Bhattacharyya SK, Idichandy VG: CFD approach to steady state analysis of an underwater glider. 2014 Oceans-St. John’s. IEEE; 2014.\n\nZhang Y, Zhang Z, Quan Z, Liu GL: Hydrodynamic performance and calculation of lift–drag ratio on underwater glider. Journal of Marine Science and Technology (Japan). Mar. 2021; vol. 26(1): pp. 16–23. Publisher Full Text\n\nStryczniewicz K, Drężek P: CFD Approach to Modelling Hydrodynamic Characteristics of Underwater Glider. Transactions on Aerospace Research. Dec. 2019; 2019(4): 32–45. Publisher Full Text\n\nCai X, Wu W, Han W, et al.: Study on Water Entry of a 3D Torpedo Based on the Improved Smoothed Particle Hydrodynamics Method. Applied Sciences (Switzerland). Jun. 2024; 14(11). Publisher Full Text\n\nKeerthi Raaj S, Saha N, Sundaravadivelu R: Exploration of deep-water torpedo anchors - A review. Ocean Engineering. Elsevier Ltd; Feb. 15, 2023; vol. 270. . Publisher Full Text\n\nGartner N, Richier M, Dune C, et al.: Hydrodynamic Parameters Estimation Using Varying Forces and Numerical Integration Fitting Method. IEEE Robot Autom Lett. 2022; 7: 11713–11719. Publisher Full Text\n\nÖzgören M, et al.: Analysis of Attack Angle Effect on Flow Characteristics Around Torpedo-Like Geometry Placed Near the Free-Surface via CFD. Politeknik Dergisi. Dec. 2021; 24(4): 1579–1592. Publisher Full Text\n\nLe TL, Hong DT: Computational fluid dynamics study of the hydrodynamic characteristics of a torpedo-shaped underwater glider. Fluids. Jul. 2021; 6(7). Publisher Full Text\n\nDivsalar K, Shafaghat R, Farhadi M, et al.: Experimental analysis on hydrodynamic coefficients of an underwater glider with spherical nose for dynamic modeling and motion simulation. SN Appl Sci. Feb. 2021; 3(2). Publisher Full Text\n\nKenan O, Yanıktepe B, Sekeroglu E, et al.: POD Analysis of Flow around Torpedo Like Geometry with a Hemispherical Nose. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi. 2023; 6(Ek Sayı): 555–566. Publisher Full Text\n\nShashank Shankar RV, Vijayakumar R: CFD estimation of HDCs for varying bodies of revolution of underwater gliders. Ocean Systems Engineering. 2023; 13(3): 269–286. Publisher Full Text\n\nSarigiguzel F, et al.: Experimental investigation of free-surface effects on flow characteristics of a torpedo-like geometry having a cambered nose. Ocean Eng. Jun. 2022; vol. 253: 111174. Publisher Full Text\n\nZhang B, Fu Y, Zhang MH, et al.: Numerical investigations into the influence of geometric configurations on hydrodynamic characteristics of torpedo anchors. Mar. Struct. Jul. 2023; 90: 103445. Publisher Full Text\n\nWon DJ, Kim J, Kim J: Design optimization of duct-type AUVs using CFD analysis. Intell. Serv. Robot. Oct. 2015; 8(4): 233–245. Publisher Full Text\n\nSoh BP, Pao W, Al-Kayiem HH: Numerical analyses for improved hydrodynamics of deep-water torpedo anchor. IOP Conference Series: Materials Science and Engineering. Institute of Physics Publishing; Dec. 2015. Publisher Full Text\n\nChoi JH, Penmetsa RC, Grandhi RV: Shape optimization of the cavitator for a supercavitating torpedo. Struct. Multidiscip. Optim. Feb. 2005; 29(2): 159–167. Publisher Full Text\n\nCao L, Zhu J, Zeng G: Viscous-flow calculations of submarine maneuvering hydrodynamic coefficients and flow field based on same grid topology. J. Appl. Fluid Mech. 2016; 9(2): 817–826. Publisher Full Text\n\nŞerifoğlu MO, Tutak B: Drag force-internal volume relationship for underwater gliders and drag coefficient estimation using machine learning. Ocean Eng. Oct. 2022; 262: 112325. Publisher Full Text\n\nTing MC, Mujeebu MA, Abdullah MZ, et al.: Numerical Study on Hydrodynamic Performance of Shallow Underwater Glider Platform.2012."
}
|
[
{
"id": "337532",
"date": "22 Nov 2024",
"name": "Shaoqiong Yang",
"expertise": [
"Reviewer Expertise My studies mainly focus on design theory",
"novel drag-reduction technology",
"and sea trial & marine application of unmanned underwater vehicles",
"especially underwater gliders."
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReview comments on the manuscript (Hydrodynamic Performance Enhancement of Torpedo-Shaped Underwater Gliders Using Numerical Techniques)\nIn the manuscript (#Hydrodynamic Performance Enhancement of Torpedo-Shaped Underwater Gliders Using Numerical Techniques), the drag reduction effect resulting from the shape optimization of the nose of a torpedo-shaped underwater vehicle was investigated via the numerical simulation method of CFD to minimize the drag of the nose. Meanwhile, based on the optimization results, the key techniques for effectively reducing the drag of underwater vehicles were identified. This manuscript provides methodological support for the hull shape design of a torpedo-shaped underwater vehicle using CFD methods, and the results of the study also have significant implications for future research on hull shape optimization. However, there are some problems with the description in the manuscript. If the problems in the manuscript can be explained and corrected in the revised version, it can be indexed. 1. In the manuscript, the authors used the term “aerodynamic performance” several times, but for the study of underwater vehicles, it is recommended to use “hydrodynamic performance” for description. 2. The figures presented in the manuscript (e.g., Figure 3) have relatively low resolution. It is suggested that figures with higher resolution be employed for display. 3. In section 3.1, it is advised to provide more detailed information on the optimization method used. 4. In section 3.1.4, it is suggested that the authors introduce the setting process of the working condition parameters in greater detail. 5. In Figure 12, the curve used to represent the \"k-elipson Standard model\" is not shown in the figure, and it is recommended to make corrections. At the same time, 'elipson' should be 'epsilon'; it is suggested to re-examine. 6. The results in Figures 23 and 24 are suggested to be combined into one figure to observe more comprehensively the influence of the changes in the bow length on the drag.\n\n7. The speed of underwater gliders is generally relatively low, can it reach over 10m/s? 8. By the way, we give some papers about the shape optimization based on CFD to authors for reference this time or communications in future:[1],[2],[3],[4],[5]\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 source data required\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
},
{
"id": "337534",
"date": "23 Nov 2024",
"name": "Denghui Qin",
"expertise": [
"Reviewer Expertise Fluid Mechanics"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article presents a numerical simulation study on the influence of different head shapes on the resistance of torpedo gliders. Among them, the results of different turbulence models and different head lengths were compared.\nComments about this paper:\n1. Figures 2 have no meaning. A scientific paper does not need to introduce literature reading and identify problems in this way. 2. Figures 3: If the author has basic knowledge of fluid mechanics, they should be aware that the resistance of the torpedo model shown in Figure 3 will be significant, as its nose does not even have a streamlined transition with its body. It is unreasonable to use a curve with high resistance as a baseline. 3. Figure 5: Why are the models of the two baselines different? 4. Table 1: These are common knowledge and do not need to be listed separately 5. Figure 8 should provide a detailed description of the size of the computational domain, as it is crucial for CFD calculations. Figures 8, 9, and 10 can all be combined into one image. 6. Figure 11 shows that the number of grids for grid independence verification should be based on the magnification factor, rather than 4.1-4.5 million 7. Figure 14-28, those figures are not suitable CFD Contours. Please refer to more CFD papers for graphics.\nBased on the comments, this paper is not proper to be indexed.\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?\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1274
|
https://f1000research.com/articles/12-1474/v1
|
15 Nov 23
|
{
"type": "Study Protocol",
"title": "Protocol for a cluster randomised controlled trial to evaluate effectiveness of a self-help group intervention to encourage smoke-free homes in slums of Kochi(Kochi Intervention for tobacco smoke free homes-KIFT)",
"authors": [
"Aswathy Sreedevi",
"Vijayakumar Krishnapillai",
"Jissa Vinoda Thulaseedharan",
"Vilma Irazola",
"Sajitha Krishnan",
"Akhilesh Kunoor",
"Jaideep Chanavil Menon",
"Goodarz Danaei",
"Vijayakumar Krishnapillai",
"Jissa Vinoda Thulaseedharan",
"Vilma Irazola",
"Sajitha Krishnan",
"Akhilesh Kunoor",
"Jaideep Chanavil Menon",
"Goodarz Danaei"
],
"abstract": "Background Exposure to second hand smoke (SHS) is a cause for heart disease and lung cancer among non- smokers. This cluster randomized control trial will evaluate the effectiveness of a tobacco smoke free home intervention in reducing exposure to second hand smoke.\n\nProtocol The intervention will be conducted among 30 clusters in urban and peri-urban areas of Kochi, India. The sample size is 300 per arm and 15 clusters to detect a minimal difference of 0.03ng/ml in cotinine levels between groups, at 80% power with a two-sided alfa of 0.05 considering variable cluster size. A baseline survey will be undertaken to identify smokers. Data related to smoking, indoor smoking, nicotine dependence, blood pressure (BP) of smokers, morbidity experienced, and lung volume Fev1/Fev6 of smokers will be measured. Urine cotinine, morbidity, BP of spouse and child will be assessed. Air quality monitors measuring PM2.5 will be placed in homes. Trained self-help group women and frontline health workers will implement the intervention. The intervention will consist of monthly home visits to educate the smoker on the harms of second-hand smoke using 3 A’s. The circle of influencers around the smoking men will also be contacted by the members of self-help group to provide support to stop smoking within homes and to quit. They will then organize two-three meetings of community leaders and heads of women’s groups, present data on harms of SHS, and explain the rationale for establishing smoke free homes in their community for a duration of six months. After the intervention a post assessment will be conducted and this will be repeated after six months.\n\nEthics and dissemination The trial protocol was approved by the Institutional Ethical Committee of Amrita Institute of Medical Sciences. Results will be submitted to open access peer reviewed journals and shared with other stakeholders.\n\nTrial registration\nCTRI/2021/06/034478",
"keywords": [
"Second hand smoke",
"Intervention",
"Tobacco smoke-free homes",
"Self-help group",
"urinary cotinine",
"PM 2.5",
"cRCT",
"3 A’s",
"Fev1/Fev6"
],
"content": "Introduction\n\nNoncommunicable diseases (NCD) are a major cause of morbidity and mortality in India. Disability-adjusted life years’ (DALYs) due to NCDs increased from 30% of the total disease burden in 1990 to 55% in 2016 and during the same period the proportion of deaths increased from 37% to 61%. Therefore, in order to halt the epidemic of NCDs, not only should sick persons be treated, but healthy persons also need to be protected.1\n\nStudies in Kerala have shown that a majority of the participants had more than one NCD risk factor. Kerala also has the highest rate of coronary artery disease (CAD)2 and diabetes in India, being in the most advanced stage of epidemiologic transition. Tobacco use, though on the decrease, is still a major risk factor for cardiovascular diseases with 20.3% of males reporting tobacco use in Kerala. Non-pharmacological measures including improving adherence to drugs and lifestyle measures including quitting tobacco are key measures in secondary prevention. Thus, concerted primary and secondary prevention strategies are required to address the future burden of NCDs.3\n\nTobacco smoking being common, exposure to second hand smoke (SHS) is a common experience among vulnerable groups such as children, women and the aged, particularly in the lower socioeconomic strata of society. It is well established that SHS is a cause of heart disease and lung cancer and could even result in death of non-smokers.4–6 Though there is a decline in the proportion of people exposed to domestic SHS in India, according to the recent GATS-2 report, it continues to be high at 38.2% among adults and 39.3% among women.7 Smoking regulations in public places alone have not resulted in substantial reductions in SHS exposure among women and children. The biggest source of involuntary exposure to tobacco smoke, particularly for children, is smoking by parents and other members of the household.8 The smoking among children in the age group of 12-19 years showed a higher prevalence among urban children and among those from poorer households.9 Studies in urban areas of Kochi showed that SHS exposure from family members among higher secondary school students was 23.2%.10\n\nThere are more than 280 slums in Kochi corporation and cardiovascular health issues are the third most common cause of morbidity according to the district government statistics.11 The formal health sector encounters slum residents only when they develop late-stage complications of preventable chronic diseases12 due to competing priorities. Slums are a manifestation of the twin challenges of rapid urbanization and the urbanization of poverty.13 Despite a National Programme for control of Non-Communicable Diseases (NP-NCD) and laws like the Cigarette and Other Tobacco Products Act (COTPA), NCDs are increasing.13 Health outcomes are worse in slums and other impoverished settlements.13,14 Therefore, in states like Kerala which has the highest burden of NCDs, progress in the control of tobacco control needs sustainable solutions embedded in the community. Due to high occupancy rates in all-purpose rooms in slums, smoking within homes can result in a high level of SHS exposure. Hence, the high population density is not only a risk factor but also an opportunity to efficiently reach a vulnerable proportion of the population.14\n\nCommunity embedded networks such as the “Kudumbashree” (which means welfare of the family) is a community network of women in the State of Kerala and has a family-based approach. These self-help groups are a community resource working in close coordination with the local self- government.15 Leveraging this group to reduce SHS exposure has good prospects. Moreover, a study on a community-based intervention by women’s self-help group members showed a reduction in blood pressure levels among people living in urban slums of Kerala, India.16 Also, our initial experience from a smoke free initiative as part of ‘Quit Tobacco international activities’ suggests that “tobacco smoke free homes initiative” were feasible and a six week campaign with self-help group members brought a 30% decline in second hand smoking in a vulnerable fisherman community.5 Therefore, intuitively, the potential impact of such interventions on reduction in second hand exposure and improvement of cardiovascular health is large. Hence this study plans to examine the effectiveness of an intervention partnering the self-help groups in reducing the second hand smoke exposure within homes.\n\nOur intention is to enhance the application of evidence in the naturally occurring clusters which are the slums. Each of the slums is a unit with similar sociodemographic features where interventions can be more effective, compliance will be better and contamination less likely. We would like to capture the population level effects of the intervention. Thus, a cluster randomisation trial was chosen.\n\nThis study aims to assess the effectiveness of a “smoke-free home” intervention in partnership with women’s self-help groups in the slums of Kochi corporation, Kerala. This is a hybrid type 2 effectiveness-implementation research combining the evaluation of effectiveness of the intervention and also assessing the implementation process. We hypothesize that a tobacco smoke-free home initiative in partnership with self-help group women will be effective in significantly reducing SHS in homes and SHS exposure among women and children of those homes over a period of 1 year. The specific aims are:\n\n• To determine the effectiveness of an intervention led by women’s self-help groups to reduce indoor tobacco smoking by measuring urinary cotinine levels and reduction in indoor smoking by measuring PM 2.5 as a surrogate for tobacco smoke in the home environment.\n\n• To correlate the urinary cotinine levels with the PM 2.5 in the home environment.\n\n• To measure the effect of the intervention on the FeV1/FeV6 among smokers.\n\n• To explore the impact of the intervention on quitting rate, smoking intensity through in depth interviews and focus group discussions.\n\n\nMethods\n\nThis will be a cluster-randomized community-based trial. Clusters will be slums with a population of more than 400 or 100 households in the Kochi Corporation and adjacent peri-urban areas. 30 clusters will be selected randomly from the sampling frame of 74 slums and colonies with a population of more than 400 population from a total list of 300 slums and colonies of Kochi Municipal Corporation and adjacent areas. These will be randomly assigned by a computer-generated table to the intervention or control arm with a 1:1 allocation ratio.\n\nEligibility: All individuals who have been living in the area for more than 6 months are eligible to participate in the study. In the households the individuals will be screened to identify homes where the male members are between 18-80 years and smoke within the homes. Such male members will be considered for the study and a participation information sheet will be given following which informed written consent will be obtained. In order to determine the impact of passive smoking their spouse or a close female relative will be administered a questionnaire following informed consent. Similarly, children in the house less than 18 years will also be administered the child questionnaire and enrolled in the study after due consent from the legally authorised representative. If there are two children in the study the youngest child older than one years will be enrolled in the study.\n\nData collection: Four semi-structured questionnaires have been developed and pretested. They include household, smoker, spouse and child questionnaires. The household questionnaire is for the household and comprises sociodemographic variables, number of family members, identifying the smokers, number of rooms, ventilation, distance from the road, type of road, any other source of air pollution within 500m, organic and inorganic waste disposal, cooking fuel used, ventilation in the kitchen, use of mosquito coils, incense sticks, and the presence of pet animals. The smokers’ questionnaire will determine smoking habits, age of initiation of smoking, types of tobacco product used, money spent on tobacco per week, quit attempts, frequency and place of smoking within home, smoking when children are around, nicotine dependence score, awareness of harmful effects of second hand smoke, and who influences smokers the most. The spouse questionnaire will consist of exposure to second hand smoke at home, practice of indoor smoking, ventilation in the kitchen, exposure to second hand smoke outside the home, cleaning habits, cooking practices, and medication use. The child questionnaire will consist of domains on reports of second-hand exposure at home and outside, history of respiratory morbidity in the past 6 months and history of hospital admission. For older children above 12 years the domains will also consist of history of tobacco use, age of initiation, and awareness regarding harm of second hand smoke. Standard methods of measurement of weight and height will be taken of the smoker, spouse and child. Blood pressure of the smoker and spouse will be measured by an electronic sphygmomanometer in a seated position after ensuring that the person is relaxed. If the reading is ≥140/90 mmHg the measurement will be repeated after 30 min and the average of the two will be taken. In order to measure FeV1/FeV6 the smokers will be instructed to take a deep breath and blow hard and long (6 seconds) till a beep is heard. The mouth should be sealed around the disposable mouthpiece. The measurement will be noted down by the health worker. We will also measure SHS through the air pollution monitor within the home which will measure particulate matter of size 2.5 microns and is a marker for the presence of SHS in the home. The device will be charged and left in the home for recording for 6-8 hours at an elevated place. The machine will record PM 2.5, 10 PM. The sensor will record the readings every 5 minutes and the output will be in the form of a graph. After downloading in the evening it will be given in the next house. This will be done at 6, 10, and 16 months respectively (Table 1).\n\nA door-to-door initial survey will be conducted following a training to the data collectors. After ascertaining the households where the male member smokes the interviews of the smoker, wife/close female relative, and child will be conducted. The interviews will be conducted separately for the husband and wife/close relative who is a woman. After the interview, Fev1/FeV6 ratio among the smokers will be assessed using a COPD 6 device. The women and child of the household will be asked to keep the urine sample in a sample bottle provided which is then placed in an auto seal pouch. These samples will be collected from all the houses and transported to the laboratory by maintaining cold chain at a temperature between 2-8 degrees C. The urinary cotinine levels among the women and children of the smoking households will be assessed in this urine sample. The cotinine levels will be assessed among the spouse of the smoker or among a woman who stays at home for a longer duration and a child up to 18 years of age. If there is more than one child in the house, the youngest child older than 1 year will be chosen. All houses may not have children; therefore, it is necessary to take both women and children’s cotinine levels. This would also be an important advocacy tool as the children’s cotinine levels can be used to influence the smoker. The urine cotinine level will be measured at 6, 10, and 16 months with the help of Cal biotech’s ELISA kit which will measure cotinine levels by ELISA (solid phase competitive ELISA). The test was calibrated and standardised in a pilot study among households of smokers and non-smokers and differences ascertained.\n\nQuality of data collected will be ensured by training and retraining of the data collectors. The data collection forms are provided.26,27 The laboratory tests will be carried out after validation. Data entry will be done with back up and range check-ups will be done for data values.\n\nFrequent meetings of the data monitoring committee (DMC) will be carried out to minimise dropout. The members of local self- government will also be taken into confidence to minimise dropout. The data monitoring committee is independent of the sponsors and is situated locally and consists of external senior public health personnel, investigators, sociologists and data analysts. The data regarding unintended effects will also be collected.\n\nBaseline survey: The initial training will be conducted for health workers to carry out the baseline survey. The content of the training will include rapport building, confidentiality, familiarisation with the questionnaires in both English and Malayalam (regional language) for the household, smoker, smoker’s spouse, and child, hands on training on data collection through open data kit (ODK) on a smart phone or tablet. Each day it will be downloaded in Excel and mailed/WhatsApp’d to the program coordinator. Hands on training of the COPD 6 device which measures FeV1/V6 will be given. Monitoring of indoor air pollution for particulate matter will also be explained in a two-day training programme.\n\nIntervention training of Self Help Group - Accredited Social Health Activist (SHG-ASHA): A three-day training and sensitisation of self-help group members and ASHAs including outlining expectations in the intervention arm will be conducted. Aspects of rapport building, confidentiality, tobacco and types of tobacco products, harms due to second hand smoke, how to change smoking behaviour (3 A’s), benefits of quitting, role and responsibility of ASHA and SHG, and sensitisation regarding the prevailing laws on tobacco and indoor air pollution will be discussed. They will be given a training booklet.\n\nThe cluster level consent has been obtained from the local self -government and individual consent will be obtained. Consent will be obtained during baseline survey and also before intervention at the local self-government level.\n\nBehavioural intervention\n\nConceptual framework: The theoretical basis for the intervention is the socioecological model. The Social Ecological Model (SEM) is a framework for understanding the multifaceted and interactive effects of personal and environmental factors that determine behaviours, and for identifying behavioural and organizational leverage points and intermediaries for health promotion within organizations.17 There are five nested, hierarchical levels of the SEM: individual, interpersonal, community, organizational, and policy/enabling environment (Figure 1). The most effective approach to public health prevention and control uses a combination of interventions at all levels of the model. At the participant/individual level the self-help group women will visit homes, use the 3 A’s of Ask, Advise and Act to speak to the smokers and their spouses to bring about behaviour change. They will use a flip chart to educate the smoker and his family on the health effects of indoor smoking. At the participant level, which is the interpersonal level in SEM, the self-help group members will talk to the influencers of the smokers. Accredited Social Health Activists (ASHAs) who are the frontline health workers will support the SHGs in implementation of the intervention. At the community and organisational level influence will be brought about by educational meetings in the ward organised by the self-help group member and by the active involvement of the elected representatives of the local self-government, other formal and informal leaders. Testimonials will be shared, the elected member will endorse the idea of smoke free homes, and video clips by leading personalities from the film industry and medical professionals will be shown. At the cluster level, children in the area will also be provided awareness so that they can convey the message in a child to parent approach among the indoor smoker households. Thus it is a composite multipronged intervention delivered by the women self-help group members comprising of face to face educational sessions singly and in groups, using influencers of the tobacco smoker, and educating the children of smokers. The self-help group member and the frontline health worker (ASHA) will be pivotal in the delivery of the intervention.\n\nThe training booklet (6-8 pages) has been developed for the ready reference of the SHG women who will deliver the intervention. The training booklet has been prepared by a team comprising a sociologist, health educator, communication specialist, community medicine expert, ASHA, and two kudumbasree workers. The training booklet will be in an easy to understand form. The training booklet will consist of a review of the burden of the problem of tobacco, particularly smoking, the problem of second hand smoke, impact on women and children, and the use of the 3 A’s in the local language. They will also contain advice on the importance of not smoking within the home. The SHG/kudumbasree members will be partners in the development of communication material and will assist in the development of a poster, leaflet, and flip chart in order to ensure clarity, relevance, easy readability and understanding.\n\nIn the intervention clusters, an air quality monitoring committee will be formed to support the intervention. This will comprise of the SHG, ASHA, junior public health nurse (female health worker), ward councilor, and members of our team. This committee will guide the intervention. In the initial two months of the intervention the SHG-ASHA team will conduct monthly home visits for educating the smoker, spouse and others in the family on the harms of second-hand smoke using a flip chart. The circle of influencers around the smoking men will also be contacted by the members of the self-help group to provide support to quit. They will then organize a meeting of community leaders and heads of women’s groups, present data on harms of SHS, explain the rationale for establishing smoke free homes in their community, and ask for their assistance in arranging other educational meetings for community members. Two-three such educational meetings will be conducted per cluster where all the household members, particularly that of the smoking households, are encouraged to attend. These meetings will be conducted at different places in the community and doctors from the nearby primary health centres will come and talk about the harms of SHS and importance of becoming a smoke free home community. In these meetings other stakeholders, formal and informal leaders of the community, and local self- government representatives will be invited.\n\nIn the next two months home visits will be conducted to paste the smoke free home stickers or distribute the calendars and reinforce the message of not smoking within homes and to get widespread recognition of the movement. Based on the findings of the baseline survey customized messages to quit will be delivered. The SHG-ASHA combined will also communicate the results of the cotinine levels and 2.5pm to the household members. The cotinine levels among the children and women will be an especially powerful tool to motivate and influence men to quit smoking within the homes and then to quit ultimately. If they express an interest to quit, they will be referred to the nearest urban primary health center for tobacco cessation. The influencers will be contacted again to encourage the smoker to quit smoking within home and to quit. Creating a movement and making “not smoking within the house an acceptable sociocultural norm” is the objective. At the end of the intervention as part of the dissemination activity smoke free homes declaration meeting for all community members in the presence of political leaders will be conducted.\n\nControl arm: The other arm will get the standard of care which would include the routine programs which are being run by the government as part of the national tobacco control program such as training of health and social workers, NGOs, school teachers, and enforcement officers; Information, Education, and Communication (IEC) activities; school programmes; monitoring of tobacco control laws; coordination with Panchayath Raj Institutions for village level activities; and setting-up and strengthening of cessation facilities including provision of pharmacological treatment facilities at district level. Periodic assessments will be done at 10 and 16 months.\n\nHealth workers will conduct end-line surveys soon after the intervention and six months after the intervention in the intervention and control arm with the same questionnaire, urinary cotinine measurement and SHS measurement with an environmental sensor. Thus the measurements will be at 6, 10 months and 16 months respectively.\n\nBased on previous studies we assume an ICC of 0.06. To detect a minimal difference of 0.03ng/ml in cotinine levels between groups,18 at 80% power with a two-sided alfa of 0.05, the estimated sample size was 113 indoor smokers per arm for individual randomization. Since one of the studies in the slum area of Ernakulam had found a prevalence of indoor smoking of 16% and considering slums above 100 households it is assumed that the expected number of smokers within household will be 20 per cluster with variability in clusters. Hence we estimated the sample size for unequal cluster size,19 with a CV of 0.45 and VIF=2.4. The estimated sample size was 271 and 14 clusters per arm. Further we assumed a drop-out rate of 10%, the final sample size was rounded to 300 per arm and 15 clusters.\n\nRandomisation\n\nThe trial has been registered in Clinical Trials Registry – India CTRI/2021/06/034478.\n\nA simple randomisation will be undertaken of the selected slums in the urban and peri-urban areas to receive intervention or not by a computer-generated random number list.\n\nAllocation concealment: Allocation will be based on clusters and the allocation will be done after the baseline survey assessment by a statistician not directly related to the study. There is no allocation concealment. All the indoor smokers will be recruited and they will be selected before randomising clusters.\n\nImplementation: Meetings will be conducted with the Kochi Corporation and District Medical Office regarding the objectives of the study. After the baseline survey, which will help to identify the indoor smokers, smoking practices, ventilation issues, and waste management practices, a simple randomisation will be undertaken of the selected slums in the urban and peri-urban areas to receive intervention or not.\n\nThe allocation sequence generation and the assignment of participants to the intervention will be carried out by the statistician and the investigators will enrol the participants.\n\nBlinding: Blinding may not be possible as a lot of people were involved, local self-government officials, the investigators team, health centres, health workers, frontline workers such as the accredited social health activist, and anganwadi workers. The group of people who collect the outcome data will be blinded.\n\nPrimary and secondary\n\nThe primary outcome is SHS exposure at homes at 10 months and 16 months as assessed by urine cotinine levels among women and or children of the smoker at the individual level. The secondary outcomes will include individual level self-reports of smoking within homes, particulate matter 2.5, harm reduction (reduction in the number of cigarettes smoked), quitting of smoking, blood pressure, Fagenstrom Nicotine dependence score, and comorbidities. Individual level assessment of Fev1/Fev6 will also be carried out with handheld spirometry considering a cut off of 73% to be indicative of COPD which is also a secondary outcome. Forced expiratory volume in 1 second (FEV1) is the maximum amount of air that the subject can forcibly expel during the first second following maximal inhalation.20 Similarly, forced expiratory volume in 6 seconds (FEV6) is the volume of forcibly exhaled air measured during 6 seconds21 which can be measured by handheld spirometry.\n\nCluster level assessment of 2.5 particulate matter in homes will also be done with air quality monitors. Monitoring and assessing intervention in terms of development of a training booklet, educational material, number of meetings organized, proportion of self-help group members in the area participating and inviting local self-government members to participate.\n\nIn order to understand the reasons for success and failure, in-depth interviews of men who have successfully quit smoking within homes, quit smoking completely, ASHAs, and health workers will be conducted. Focus group discussions of wives of smokers who quit smoking within homes and those who reduced the number of cigarettes will be conducted.\n\nData analysis and statistical plan: Data will be entered electronically on a secure file storage system and password protected. Data will be anonymised by assigning a unique identification number to each smoker. Outcome data will be reported in accordance with the Standard Protocol Items: Recommendation for Intervention Trials (SPIRIT). All the smokers will be included in the analysis regardless of reduction in smoking within homes.\n\nParticipant flow\n\n30 clusters will be randomly assigned into two groups and will receive intended intervention and will be analyzed for primary outcome of urinary cotinine. For each group losses and exclusion of clusters and individual participants will be recorded (Figure 1).\n\nBaseline data: The baseline data will be presented for both clusters and individuals as the risk of chance imbalances are greater with clusters.\n\nNumbers analyzed: We plan to analyze 30 clusters with at least 300 indoor smokers in each arm. The urine cotinine of the women and children will be obtained from 300 women and or children in each arm. The indoor home values of 2.5 PM will be obtained from 300 households in each arm. Similarly, the lung function values as indicated by FeV1/FeV6 will be assessed among 300 each in the intervention and control group.\n\nOutcomes and estimation: The difference in mean cotinine levels among the clusters in the intervention and control group with 95% CI will be estimated. The intracluster correlation coefficient for each outcome will be reported. Adjusted estimates of clustering will also be provided. Cox’s proportional hazards will be calculated for quitting, harm reduction, blood pressure values. This is to determine the effectiveness of an intervention based on partnering with women’s SHG’s to reduce indoor tobacco smoking by measuring urinary cotinine levels.\n\nA repeated-measures ANOVA will be used to compare the mean urinary cotinine concentration between groups, before and after intervention.\n\nAnalysis for self-reported quit rates will be assessed by a Cox proportional hazards model. Generalised linear mixed effect models will be used to test between cluster differences from baseline to each follow up period for each outcome indicator.\n\nWe will use an intention to treat approach in analysis. A multilevel model will be used for analysis using the generalized linear mixed effect model which will also adjust for individual covariates. Key variables will be measured at baseline and then compared between arms to check balance; and if both arms are unbalanced with respect to any relevant factors, which can happen given that the unit of randomization is the cluster instead of the individual, those factors will be adjusted for in the final analysis so as to address potential confounding. Analysis for SHS exposure rates and quit rates will be assessed by a Cox proportional hazards model.\n\n• To correlate the urinary cotinine levels with the second-hand smoke in the home environment: correlation and linear regression analysis will be carried out by Pearson’s correlation if it follows a normal distribution and Spearman if it is a non-normal distribution.\n\nThe difference in cotinine levels will be analysed by comparing the urine level of cotinine at the end of follow up, adjusted for the baseline value, by using linear mixed model or GEE to allow for cluster effect.\n\n• To measure the effectiveness of the intervention among smokers by measuring their FeV1/FeV6 using COPD6.\n\nTo determine the effectiveness of the intervention in improvement of lung function the ratio of FeV1/FeV6 will be measured pre- and post-intervention and the mean difference between the groups will be assessed by a paired t-test.\n\nQualitative data analysis\n\nInterview guides will be developed for in-depth interviews, key-informant interviews and focus group discussions by extensive formative research with literature reviews and taking expert opinions. A list of pre-determined open-ended questions will be used in the interview guides. Probing questions will be asked to explore the topic in-depth. An informed verbal consent will be obtained for participating in the interview and for audio recording the session. The interviews will then be conducted in the regional language, Malayalam. The audio recorded data will be then transcribed verbatim and translated to English. The typed transcripts will then be reviewed for accuracy, completion and familiarization and then manually coded to identify the emerging themes and subthemes. Semi-structured interviews and focus groups will be audio-recorded, transcribed verbatim and anonymised before being coded. Conclusions will then be arrived at by data triangulation.\n\nData will be analysed inductively using the grounded theory. Appropriate codes and sub-codes will be generated. Data will be analysed thematically to elicit appropriate themes and sub-themes. Interviews in local languages will be transcribed and the analysis will be conducted by researchers fluent in these languages.\n\nTo understand the impact of the intervention among smokers who quit, those who showed reduced smoking, those who did not stop smoking within homes, and households where the smokers stopped smoking within homes, focus group discussions will be conducted with spouses of the smokers. These focus group discussions will enable the participants to share their experience. Focus group discussions will comprise of 6-8 wives of smokers who quit smoking within homes and or those who reduced the number of cigarrettes/bidis. The other focus groups will be with those who have quit or reduced the number of cigarettes smoked and among those who have not, in order to identify barriers to smoking cessation within homes. The focus groups will also seek to identify factors that affected participation in the meetings, motivation due to the educational sessions, and the factors that most helped to quit smoking within homes or cessation or harm reduction.\n\nThe fidelity of the intervention will be assessed by the number of meetings conducted in an area, the number of smoking persons and household members attending, and the number of influencers of smokers contacted. At the end of the study focus group discussions will be conducted among 6-8 quitters, those who have reduced the number of cigarettes/bidis smoked and those who did not make any change at all. Apart from the focus group discussions, in-depth interviews will be conducted with the self-help group volunteers. These interviews will be conducted at the end of the intervention among about self-help group volunteers who were part of the intervention, councillors, urban primary health centre MO, and a junior public health nurse to identify the key elements that might have helped in effective implementation and good outcomes.\n\nEthical issues: Any adverse events will be recorded and reported to the Chair of the Trial Steering Committee and the Chair of the Ethics Committee. Institutional Ethical Committee approval has been obtained vide letter dated 18-10-2022 from Amrita Institute of Medical Sciences (IEC-AIMS-2022-COMM-284). The protocol V2 was submitted and approved by ethical committee vide above. Informed consent and assent will be obtained from the respective participants by the coordinator of the study. The investigators will only have access to the data.\n\nDissemination: A dissemination will be carried out in Kochi with the participation of all stakeholders. The results of the study will be disseminated to all the stakeholders including the community, state and district NCD control officers. Following this the results will also be disseminated through publication.\n\nPublic involvement: The local self-government has been taken into confidence and they are fully supportive of this venture. Local steering committees have been formed in the intervention clusters to guide and support the intervention.\n\nCurrently the baseline data collection is ongoing.\n\n\nDiscussion\n\nGeneralizability: To our knowledge, this is the first trial in India that will investigate the effectiveness of a self-help group led intervention in household where there is indoor smoking. The current study builds on a promising pilot trial which gave the proof of concept of this study.4 Public engagement will continue to be central to this study which enhances the acceptability of the intervention and ensures sustainability.\n\nAs far as generalizability is concerned it will be generalizable to similar clusters and individuals inhabiting such clusters rather than to metropolitan areas.\n\nThe conceptual framework is the socioecological model which is important in understanding and determining behaviour change. As an implementation research, it seeks to assess impact by the RE-AIM framework (Table 2). There is mounting interest in the use of theories, models and frameworks to gain insights into the mechanisms by which implementation is more likely to succeed.22 Implementation research is intended to improve people’s health through informed policies, strengthened service delivery.23 The implementation outcome variables are acceptability, adoption, appropriateness, feasibility, fidelity, coverage and sustainability. The large number of contextual factors that affect implementation can interact with each other and change over time which points to the fact that implementation occurs as part of complex adaptive systems.24,25\n\nThough the RE-AIM network was developed to help make research findings more generalisable when developing and testing interventions, it also helps to plan strategies that can reach most people, effectively achieve and maintain positive health outcomes, be adopted in varied settings and be consistently implemented at a reasonable cost and be sustained in different kind of settings. At the end of the intervention, declaration meeting will be held where Mayor and other officials, elected representatives, health officials and press will attend. If the intervention is found to be successful, this will help in creating policies for smoke free homes.\n\nEthical considerations: Institutional Ethical Committee approval has been obtained vide letter dated 18-10-2022 of Amrita Institute of Medical Sciences (IEC-AIMS-2022-COMM-284). Data collection will be done after getting informed consent and or assent. Assent will also be obtained from children above 11 years and parental consent from those below 11 years.\n\n\nEthics approval and consent to participate\n\nInstitutional ethical Committee approval has been obtained vide letter dated 18-10-2022 vide Institutional Ethical Committee of Amrita Institute of Medical Sciences (IEC-AIMS-2022-COMM-284). Informed consent will be taken from all participants or parents/legal guardians of minors to participate in the study.",
"appendix": "Data availability\n\nNo underlying data are associated with this article.\n\nfigshare: Eng Questionnaire. https://doi.org/10.6084/m9.figshare.24468202.v1 26\n\nThis project contains the English language version of the questionnaire that will be used in the study.\n\nfigshare: Questionnaire for Tobacco Smoke-Free Homes. https://doi.org/10.6084/m9.figshare.24314530.v1 27\n\nThis project contains the original questionnaire that will be used in the study.\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 the support of Ms Sreeshma VN, Dr Vishnu B Menon and Ms Kavya.\n\n\nReferences\n\nNon Communicable Diseases/National Health Portal of India nhp.gov.in Healthy living ncd.2019.\n\nIndia State-Level Disease Burden Initiative Collaborators: Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study. Lancet 2017; 2017(390): 2437–2460.\n\nSarma PS, Sadanandan R, Thulaseedharan JV, et al.: Prevalence of risk factors of non-communicable diseases in Kerala, India: results of a cross- sectional study. BMJ Open 2019; 9: e027880. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWindham GC, Eaton A, Hopkins B: Evidence for an association between environmental tobacco smoke exposure and birthweight: a metaanalysis and new data. Paediatr. Perinat. Epidemiol. 1999; 13: 35–57. PubMed Abstract | Publisher Full Text\n\nMimi N, Sreedevi P, Mark M, et al.: Developing a smoke free homes initiative in Kerala, India. BMC Public Health 2015; 15: 480. Publisher Full Text\n\nKing BA, Mirza SA, Babb S, et al.: A cross country compilation of second hand smoke exposure among adults: findings from the Global adult tobacco survey (GATS). Tob. Control. 2013; 22: e5. Publisher Full Text\n\nGATS-2 Fact sheet: International Institute for population sciences (IIPS),Mumbai. Global adult tobacco survey (GATS, India),2016-17,New Delhi, Ministry of health and family welfare. Govt of India2017.\n\nBritton J: Smoke free policy and child health. Lancet-Public Health. Sep 2017; 2: e392–e393. Publisher Full Text\n\nJayasoorya, Beena KN, Beena M, et al.: Prevalence & correlates of tobacco use among adolescents in Kerala. Indian J. Med. Res. 2016; 144(5): 704. Publisher Full Text\n\nRakesh PS, Lalu JS, Leelamoni K: Prevalence of exposure to secondhand smoke among higher secondary school students in Ernakulam District, Kerala, Southern India. J. Pharm. Allied Sci. 2017; 9(1): 44–47. Publisher Full Text\n\naccessed on 11 nov2017. Reference Source\n\nAlon U, Lee WR: SlumHealth:from understanding to action. PLoSMedicine. Oct 2007; 4.\n\nSzwarcwald CL, Andrade CL, Bastos F: Incomeinequality,residential poverty clustering and infant mortality; a study in Rio de janerio, Brazil. Soc. Sci. Med. 2002; 55: 2083–2092. PubMed Abstract | Publisher Full Text\n\nSclar ED, Garau P, Carolini G: the 21st century health challenge of slums and cities. Lancet. 2005; 365: 901–903. PubMed Abstract | Publisher Full Text\n\nJose J: Role of Kudumbasree and women empowerment: A study of Thiruvananthapuram Municipality. Int. J. Res. December, 2015; 3(12).\n\nSuseela PR, Ambika RB, Mohandas S, et al.: Effectiveness of a community- based education and peer support led by women’s self-help groups in improving the control of hypertension in urban slums of Kerala, India: a cluster randomised controlled pragmatic trial. BMJ Glob. Health 2022; 7: e010296. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBronfenbrenner U: Ecological systems theory.Vasta R, editor. Annals of Child Development. Vol. 6. . London, UK: Jessica Kingsley Publishers; 1989; pp. 187–249.\n\nMatarese A, Sardu C, Shu J, et al.: Why is chronic obstructive pulmonary disease linked to atrial fibrillation? A systematic overview of the underlying mechanisms. Int. J. Cardiol. 2019 Feb 01; 276: 149–151. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPan MM, Zhang HS, Sun TY: Value of forced expiratory volume in 6 seconds (FEV(6)) in the evaluation of pulmonary function in Chinese elderly males. Zhonghua Yi Xue Za Zhi 2017 May 30; 97(20): 1556–1561. PubMed Abstract | Publisher Full Text\n\nAbdullah AS, Hua F, Khan H, et al.: Secondhand Smoke Exposure Reduction Intervention in Chinese Households of Young Children: A Randomized Controlled Trial. Acad. Pediatr. 2015; 15(6): 588–598. PubMed Abstract | Publisher Full Text\n\nHemming, et al.: Sample size calculations for cluster randomised controlled trials with a fixed number of clusters. BMC Med. Res. Methodol. 2011; 11: 102. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNilsen P: Making sense of implementation theories, models and frameworks. Implement. Sci. 2015; 10: 53. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGlasgow RE, Chambers D: Developing robust, sustainable, implementation systems using rigorous, rapid and relevant science. Clin. Transl. Sci. 2012; 5: 48–55. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGlasgow RE, Vogt TM, Boles SM: Evaluating the public health impact of health promotion interventions:the RE-AIM framework. Am. J. Public Health 1999; 89(9): 1322–1327. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPaina L, Peters DH: Understanding pathways for scaling up health services through the lens of complex adaptive systems. Health Policy Plan. 2012; 27: 365–373. PubMed Abstract | Publisher Full Text\n\nSreedevi A: Eng Questionnaire. figshare. Journal Contribution. 2023. Publisher Full Text\n\nSreedevi A: Questionnaire for Tobacco Smoke-Free Homes. figshare. Journal Contribution. 2023. Publisher Full Text"
}
|
[
{
"id": "224000",
"date": "27 Jan 2024",
"name": "Brijesh Sathian Hamad",
"expertise": [
"Reviewer Expertise Clinical trials"
],
"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\nProvide more literature review for the gap analysis and importance to Kerala. What is the current burden of noncommunicable diseases (NCDs) in India, particularly in Kerala, and how has it evolved over time? How does exposure to second-hand smoke (SHS) contribute to the burden of NCDs, especially in vulnerable populations like children, women, and the elderly? What are the main risk factors for cardiovascular diseases in Kerala, and how do these risk factors vary among different demographic groups? How effective have past tobacco control measures been in reducing SHS exposure, particularly within households, in India, and what are the ongoing challenges? What role do slums play in contributing to the burden of cardiovascular health issues, and how does the formal healthcare sector currently address health concerns in these communities? What is the significance of community networks, such as \"Kudumbashree,\" in the context of public health interventions, and how have they been utilized in previous health-related initiatives in Kerala? Can community-based interventions, especially those involving women's self-help groups, effectively contribute to reducing SHS exposure in households and improving cardiovascular health outcomes? How has the implementation of smoke-free initiatives, particularly those involving self-help group members, demonstrated feasibility and effectiveness in previous studies or initiatives? What evidence supports the hypothesis that a \"tobacco smoke-free home\" initiative in partnership with self-help group women can significantly reduce SHS exposure in homes and improve health outcomes over a one-year period? Provide more details about the sample size calculation and the ICC selection. How will be the inter cluster variation measured? provide more details about the machine which will be used to measure FeV1/FeV6.\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": [
{
"c_id": "11201",
"date": "28 Nov 2024",
"name": "Aswathy Sreedevi",
"role": "Author Response",
"response": "Provide more literature review for the gap analysis and importance to Kerala. What is the current burden of noncommunicable diseases (NCDs) in India, particularly in Kerala, and how has it evolved over time? Thank you. Has been provided now in the first two paragraphs of introduction “Noncommunicable diseases (NCD) are a major cause of morbidity and mortality in India. The disease transition in India in the past 2 decades is representative of the accelerated epidemiological transition model with a rapid shift to the age of delayed chronic diseases.1 Therefore, in order to halt the epidemic of NCDs, not only should sick persons be treated, but healthy persons also need to be protected. 2 In Kerala, 90% of premature mortality in the 15-69 year age group is attributed to NCD.3 Kerala also has the highest rate of coronary artery disease (CAD) 3and diabetes in India, being in the most advanced stage of epidemiologic transition. Over the years the prevalence of Cardiovascular disease has seen an increase with cardiovascular disease accounting for 15.2% of total death in 1990 to 28.1% of total deaths in 2016 and more than half (53.4% ) of crude deaths due to CVD were among people younger than 70 yrs.4 While cardiovascular disease risk factors encompass diet, obesity, systolic blood pressure, and air pollution, tobacco use, despite its declining prevalence, consistently ranks among the top six risk factors.4,5 Another risk factor study in Kerala pointed to the dismal fact that only a fifth of the study population; 20.4% of men and 16.5% were free of any of the seven NCD risk factors studied- tobacco use, alcohol use, obesity, abdominal obesity, raised BP, raised blood glucose or physical inactivity. Three or more risk factors were present in 20.9% and four or more NCD risk factors were present in 6.4% of the participants.6” How does exposure to second-hand smoke (SHS) contribute to the burden of NCDs, especially in vulnerable populations like children, women, and the elderly? Chronic exposure to SHS is suggested to be, on average, 80%–90% as harmful as chronic active smoking with a significant dose-response relationship. 10-12 SHS affects the heart and blood vessels, increasing the risk of myocardial infarction, stroke, and emotional changes like depression in non-smokers. Smokers’ children suffer reduced lung function, which continues to affect them in the form of chronic respiratory disorders in adulthood. School-aged children exposed to the harmful effects of second-hand smoke are also at risk for asthma through inflammation of the airways to the lungs.13 What are the main risk factors for cardiovascular diseases in Kerala, and how do these risk factors vary among different demographic groups? While cardiovascular disease risk factors encompass diet, obesity, systolic blood pressure, and air pollution, tobacco use, despite its declining prevalence, consistently ranks among the top six risk factors.4,5 Another risk factor study in Kerala pointed to the dismal fact that only a fifth of the study population; 20.4% of men and 16.5% were free of any of the seven NCD risk factors studied- tobacco use, alcohol use, obesity, abdominal obesity, raised BP, raised blood glucose or physical inactivity. Three or more risk factors were present in 20.9% and four or more NCD risk factors were present in 6.4% of the participants.6 How effective have past tobacco control measures been in reducing SHS exposure, particularly within households, in India, and what are the ongoing challenges? What role do slums play in contributing to the burden of cardiovascular health issues, and how does the formal healthcare sector currently address health concerns in these communities? Not much .The COTPA Act and its limitation in addressing exposure at smoke and the exposure as reported among school children has been mentioned. The tobacco control laws particularly section 4 apply to public places and as has been mentioned in para2 biggest source is involuntary exposure at home What is the significance of community networks, such as \"Kudumbashree,\" in the context of public health interventions, and how have they been utilized in previous health-related initiatives in Kerala? This has been added. Can community-based interventions, especially those involving women's self-help groups, effectively contribute to reducing SHS exposure in households and improving cardiovascular health outcomes? Thank you for pointing this out. They have been added and listed. Throughout the world, diverse community leaders and organizations has been explored,26,27,28 which were feasible with varying degrees of effectiveness. Moreover, a study on a community-based intervention by women’s self-help group members showed a significant reduction in blood pressure levels among people living in urban slums of Kerala, India. 29 Also, our initial experience from a smoke free initiative as part of ‘Quit Tobacco international activities’ suggests that “tobacco smoke free homes initiative” were feasible and a six week campaign with self-help group members brought a 30% decline in second hand smoking in a vulnerable fisherman community. 30 Therefore, intuitively, the potential impact of such interventions on reduction in second hand exposure and improvement of cardiovascular and respiratory health is large. Hence this study plans to examine the effectiveness of an intervention partnering the self-help groups in reducing the second hand smoke exposure within homes. How has the implementation of smoke-free initiatives, particularly those involving self-help group members, demonstrated feasibility and effectiveness in previous studies or initiatives? Added What evidence supports the hypothesis that a \"tobacco smoke-free home\" initiative in partnership with self-help group women can significantly reduce SHS exposure in homes and improve health outcomes over a one-year period? The evidence as below Throughout the world, diverse community leaders and organizations has been explored,26,27,28 which were feasible with varying degrees of effectiveness. Moreover, a study on a community-based intervention by women’s self-help group members showed a significant reduction in blood pressure levels among people living in urban slums of Kerala, India. 29 Also, our initial experience from a smoke free initiative as part of ‘Quit Tobacco international activities’ suggests that “tobacco smoke free homes initiative” were feasible and a six week campaign with self-help group members brought a 30% decline in second hand smoking in a vulnerable fisherman community. 30 Therefore, intuitively, the potential impact of such interventions on reduction in second hand exposure and improvement of cardiovascular and respiratory health is large. Hence this study plans to examine the effectiveness of an intervention partnering the self-help groups in reducing the second hand smoke exposure within homes. Provide more details about the sample size calculation and the ICC selection. How will be the inter cluster variation measured? Thank you for this question. The reference for ICC has been added. The mode of calculation of sample size is as below. Ref: Hemming et al. BMC Medical Research Methodology 2011, 11:102 Sample size under individual randomization mean 1: 0.09 mean 2: 0.06 standard deviation 1: 0.08 standard deviation 2: 0.08 significance level: 0.05 power: 0.80 n= 113 per arm (using equation3) Standard sample size under cluster randomization (where the cluster size are unequal) Here, the SD of cluster size is approximately 9 (range/4 = (40-4)/4 =36/4 =9) And an average cluster size of 20. Hence, Coefficient of variation of cluster sizes (CV) = 9/20 = 0.45 Variance Inflation Factor (Design effect) = 2.4 (using equation 6) Then the required sample size per arm, nc= n xVIF (using equation 8) = 113*2.4 =271.2 rounded to 271 Number of clusters = 113*2.4/20 (using equation 10) = 13.6 rounded to 14 clusters per arm Again adjusting for a 10% drop out rate, the sample size per arm is increased to 300 provide more details about the machine which will be used to measure FeV1/FeV6. The portable spirometer is a device manufactured by Vitalograph and used to measure lung capacity. This has been added “After the interview, Fev1/FeV6 ratio among the smokers will be assessed with the Vitalograph COPD-6 screener device” The Vitalograph copd-6 is an accurate and cost effective ‘case selection’ or screening device that identifies potential cases of COPD Identifies those at risk of COPD at the pre-symptomatic stage Screens out those whose FEV1 is normal, without the risk of false negatives Displays the key parameters for clinical interpretation including obstructive index and COPD classification (stage I – IV) Displays FEV1, FEV6, ratio and % predicted, obstructive index, COPD classification and lung age Detachable flowhead makes cleaning simple Built-in quality of blow indicator Designed for multi-subject use"
}
]
},
{
"id": "236524",
"date": "01 Feb 2024",
"name": "Sophie Orton",
"expertise": [
"Reviewer Expertise Secondhand smoke exposure in the home",
"smoking in pregnancy and postpartum"
],
"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 protocol for a cluster randomised controlled trial to evaluate the effectiveness of s smoke-free homes intervention in Kochi, India. The protocol describes a complex intervention clearly and concisely. The rationale for, and objectives of the study are clearly described, although below I give some recommendations to improve the objectives in particular. The study design is appropriate for the research question, and there are sufficient details of the methods to allow replication by others. The below comments are recommendations to aid clarity.\nIntroduction: The introduction nicely sets the scene for this research, and helps the reader understand the setting of the intervention. A few additions are recommended: Paragraph 3: What are the smoking regulation in public places, and when were they introduced? Are there any estimates of female tobacco use in Kerala? (If very low, this will help to justify why only screening male household members for eligibility) SHS exposure among children has been associated with a wide range of health conditions. The introduction would benefit from referencing these, as currently it implies that the main negative health outcomes of SHS exposure is heart disease and lung cancer, where as we know children are particularly vulnerable to other health consequences of SHS exposure. “Smoking among children in the age group of 12-19 years showed a higher prevalence among urban children and among those from poorer households’ – it is not clear the relevance of this sentence within this paragraph. Are the authors indicating children/young people are more likely to smoke if exposed to secondhand smoke? Please clarify this statement. Paragraph beginning “Community embedded networks…” – are there any other examples internationally of interventions to reduce smoking in the home that have informed this work? Please could the authors provide a reference for the term ‘hybrid type 2 effectiveness-implementation research’. Objective 1: rather than ‘surrogate’, is urinary cotinine and PM 2.5 an ‘indicator’ for tobacco smoke exposure in the home?\nObjectives generally: The introduction at present does not clearly lead to the objectives, i.e. urinary cotinine, PM 2.5 and FeV1/FeV6 have not been introduced previously, and so it is not clear to the general reader why these are the outcomes of importance. The introduction would benefit from a paragraph introducing urinary cotinine, PM 2.5 and FeV1/FeV6, what relevance they have to secondhand smoke exposure. How are these measured? How are they associated with secondhand smoke exposure? Are they commonly used measures/indicators for secondhand smoke exposure (please reference previous similar studies that have used these). In particular, what is the importance of measuring FeV1/FeV6 among smokers? Objective “To explore the impact of the intervention on quitting rate, smoking intensity through in depth interviews and focus group discussions” – is this an intervention to reduce smoking in the home, or to reduce smoking rates? Why would the authors expect a change in smoking quit rates? Can the authors give examples in the background where smoking in the home interventions have also led to increased quit rates among smokers? If this is a secondary outcome, suggest having this as another subheading ‘secondary outcome’.\nMethods Please could the authors use an appropriate reporting tool? E.g. CONSORT\nData collection: please reference which nicotine dependence scale you are using in the text.\nIntervention training of self-help group – who are the self help group and how will they be identified/recruited? Outcomes, primary and secondary: will there be cut-points for the urinary cotinine levels? Or change in urinary cotinine?\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": "11202",
"date": "13 Apr 2024",
"name": "Aswathy Sreedevi",
"role": "Author Response",
"response": "Paragraph 3: What are the smoking regulation in public places, and when were they introduced? Are there any estimates of female tobacco use in Kerala? (If very low, this will help to justify why only screening male household members for eligibility) Smoking regulations in public places such as hotels, theatres are prohibited and are governed by Section 4 of the Cigarette and other tobacco products Act(COTPA),2003.14 However, this alone has not resulted in substantial reductions in SHS exposure among women and children. These are largely from men in the households as women smokers are very low (0.2%-2.2%) in Kerala. 19,20 According to GATS-2(https://ntcp.mohfw.gov.in/assets/document/surveys-reports-publications/GATS-2-FactSheet.pdf )it was 0.2%and according to NFHS survey 5 in 2019-2020 it was only 2.2% (https://www.im4change.org/docs/Kerala%20NFHS-5%20Factsheet.pdf). SHS exposure among children has been associated with a wide range of health conditions. The introduction would benefit from referencing these, as currently it implies that the main negative health outcomes of SHS exposure is heart disease and lung cancer, where as we know children are particularly vulnerable to other health consequences of SHS exposure. Thank you. The following paragraph has been added. “Chronic exposure to SHS is suggested to be, on average, 80%–90% as harmful as chronic active smoking with a significant dose-response relationship. 10-12 SHS affects the heart and blood vessels, increasing the risk of myocardial infarction, stroke, and emotional changes like depression in non-smokers. Smokers’ children suffer reduced lung function, which continues to affect them in the form of chronic respiratory disorders in adulthood. School-aged children exposed to the harmful effects of second-hand smoke are also at risk for asthma through inflammation of the airways to the lungs.13” “Smoking among children in the age group of 12-19 years showed a higher prevalence among urban children and among those from poorer households’ – it is not clear the relevance of this sentence within this paragraph. Are the authors indicating children/young people are more likely to smoke if exposed to secondhand smoke? Please clarify this statement. Yes-that’s what we are trying to say. Hope the following statement makes it clear. “Smoking among children in the age group of 12-19 years was found to be higher among urban children and among those from poorer households. 16 There are also studies which point to the fact that those who report ever-use of tobacco are more likely to have experienced exposure to SHS at home.17” Paragraph beginning “Community embedded networks...” – are there any other examples internationally of interventions to reduce smoking in the home that have informed this work? They have been added “Throughout the world, diverse community leaders and organizations has been explored,26,27,28 which were feasible with varying degrees of effectiveness. Moreover, a study on a community-based intervention by women’s self-help group members showed a significant reduction in blood pressure levels among people living in urban slums of Kerala, India. 29 Also, our initial experience from a smoke free initiative as part of ‘Quit Tobacco international activities’ suggests that “tobacco smoke free homes initiative” were feasible and a six week campaign with self-help group members brought a 30% decline in second hand smoking in a vulnerable fisherman community. 30” Please could the authors provide a reference for the term ‘hybrid type 2 effectiveness- implementation research’. Has been provided Objective 1: rather than ‘surrogate’, is urinary cotinine and PM 2.5 an ‘indicator’ for tobacco smoke exposure in the home? Thank you. The word surrogate has been replaced by indicator Objectives generally: The introduction at present does not clearly lead to the objectives, i.e. urinary cotinine, PM 2.5 and FeV1/FeV6 have not been introduced previously, and so it is not clear to the general reader why these are the outcomes of importance. Thank you for pointing this omission out .Now they have been introduced. The introduction would benefit from a paragraph introducing urinary cotinine, PM 2.5 and FeV1/FeV6, what relevance they have to secondhand smoke exposure. How are these measured? How are they associated with secondhand smoke exposure? Are they commonly used measures/indicators for secondhand smoke exposure (please reference previous similar studies that have used these). Outcomes of the intervention need to measure exposure to second hand smoke. Biomarkers and indicators of environmental pollution were considered. Urinary cotinine level is a widely used biomarker and has a good correlation with daily tobacco consumption and second hand exposure. 31 Urine cotinine concentrations are more sensitive than in blood or saliva, making urine a sensitive matrix to detect low-concentration exposure. 32,44 Particulate matter(PM), despite a background concentration of respirable particulate matter (PM) due to cooking and infiltration from outdoors, is considered a good indicator of SHS, at relatively high levels. 28,33 PM < 10 μm enter the respiratory tract, but may be the result of mechanical processes such as construction activities, road dust resuspension and wind whereas PM < 2.5 μm (fine particles) originate primarily from combustion sources such as smoking. 34 Quit rates and harm reduction are also outcomes which will be reported as has been observed in other studies. 35,36 . They have been added with studies that have used them (33,44) In particular, what is the importance of measuring FeV1/FeV6 among smokers? In order to assess the impact of the intervention on smokers perse FEV1/FEV6 was measured. This measure is a substitute for FEV1/FVC in diagnosing airflow obstruction and may better predict COPD-related pathology and morbidity. 37 The use of 6-s expiratory maneuvers makes handheld spirometry faster and easier, provides a more explicit end-of-test definition. Its use in primary care has also been demonstrated for the detection of COPD in adults. 38 Objective “To explore the impact of the intervention on quitting rate, smoking intensity through in depth interviews and focus group discussions” – is this an intervention to reduce smoking in the home, or to reduce smoking rates? Why would the authors expect a change in smoking quit rates? Can the authors give examples in the background where smoking in the home interventions have also led to increased quit rates among smokers? If this is a secondary outcome, suggest having this as another subheading ‘secondary outcome’. It has been mentioned under secondary outcome only. “Quit rates and harm reduction are also outcomes which will be reported as has been observed in other studies. 35,36” A study which investigated whether cessation rates varied by changes in home smoking ban implementation between enrollment and 7-month follow-up found a higher cessation among those who Among callers who did not live with other smokers in the home, the highest odds ratio of 30-day cessation was observed among callers. (Yuan NP, Nair US, Crane TE, Krupski L, Collins BN, Bell ML. Impact of changes in home smoking bans on tobacco cessation among quitline callers. Health Educ Res. 2019 Jun 1;34(3):345-355. doi: 10.1093/her/cyz008. PMID: 30932151; PMCID: PMC6510015.)Another study in 20 LMIC reported that Smokefree homes were associated with reduced cigarettes per day in all daily smokers. (Daniel Owusu, Megan Quinn, Kesheng Wang, Faustine Williams, Hadii M. Mamudu, Smokefree home rules and cigarette smoking intensity among smokers in different stages of smoking cessation from 20 low-and-middle income countries,Preventive Medicine, Volume 132,2020,106000,ISSN 0091-7435). Methods Please could the authors use an appropriate reporting tool? E.g. CONSORT Thank you. We have used the SPIRIT guidelines according to the journal guidelines Data collection: please reference which nicotine dependence scale you are using in the text. Thank you for pointing this out. This has now been added -Fagenstrom dependence scale. Intervention training of self-help group – who are the self help group and how will they be identified/recruited? The self- help group are an arm of the Local self- government created for social empowerment, economic empowerment and women empowerment. The list is available with the local self- government[DS1] and the community is also aware about its members. Similarly the ASHA is the frontline health worker and is known to all the people. Outcomes, primary and secondary: will there be cut-points for the urinary cotinine levels? Or change in urinary cotinine? Change in mean/median values will be considered. It has been added Methods We have used the SPIRIT protocol as is the guideline of the F1000 journal. Data collection: the Fagenstrom nicotine dependence test. The self- help group are an arm of the Local self- government created for social empowerment, economic empowerment and women empowerment. The list is available with the local self- government and the community is also aware about its members."
}
]
}
] | 1
|
https://f1000research.com/articles/12-1474
|
https://f1000research.com/articles/13-1271/v1
|
24 Oct 24
|
{
"type": "Research Article",
"title": "Molecular docking and MD simulation approach to identify potential phytochemical lead molecule against triple negative breast cancer",
"authors": [
"Pranaya Sankaranarayanan",
"Dicky John Davis G",
"Abhinand PA",
"M Manikandan",
"Arabinda Ghosh",
"Pranaya Sankaranarayanan",
"Abhinand PA",
"M Manikandan",
"Arabinda Ghosh"
],
"abstract": "Background Triple-negative breast cancers are defined as tumors that lack the expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It exhibits unique clinical and pathological features, is highly aggressive, and has a relatively poor prognosis and poor clinical outcome.\n\nObjective To identify a novel drug target protein against triple-negative breast cancer (TNBC) and potential phytochemical lead molecules against novel drug targets.\n\nMethods In this study, we retrieved TNBC samples from NGS and microarray datasets in the Gene Expression Omnibus database and employed a combination of differential gene expression studies, protein-protein interaction analysis, and network topology investigation to identify the target protein. Using molecular docking and molecular dynamics simulation studies, followed by Molecular Mechanics with Generalised Born Surface Area solvation, a potential lead molecule was identified.\n\nResult The androgen receptor (AR) was found to be the target protein, and 2-hydroxynaringenin was discovered to be a possible phytochemical lead molecule to combat TNBC. Upregulated genes with LogFC > 1.25 and P-value < 0.05 from the TNBC gene expression dataset were given to STRING tool to investigate the network topology, and androgen receptor (AR) was found to be an appropriate hub gene in the protein-protein interaction network. Phytochemicals that inhibit breast cancer were retrieved from the PubChem database and virtual screening was performed using PyRx against the AR protein. Based on Lipinski’s rule and ADMET properties, molecular interaction studies were analyzed using induced fit docking, wherein significant binding interactions were displayed by 2-hydroxynaringenin. Molecular dynamics studies and MM-GBSA of AR and the 2-hydroxynaringenin complex revealed strong and stable interactions.\n\nConclusion AR was identified as a hub protein that is highly expressed in breast cancer and 2-hydroxynaringenin efficacy of counter TNBC needs to be investigated further in vitro and in vivo.",
"keywords": [
"Triple Negative Breast Cancer",
"AR target",
"Phytochemicals",
"2–hydroxy naringenin",
"Virtual screening",
"Molecular Docking",
"Molecular dynamics simulation."
],
"content": "Introduction\n\nBreast cancer is the most common type of cancer worldwide, as reported by the World Health Organization (WHO) in 2020 with over 7.8 million women living in the last five years diagnosed with breast cancer.1 It is responsible for 685,000 deaths worldwide. However, it should be noted that breast cancer is a non-homogenous condition that can be classified into several significant subtypes based on the expression of their genes. Triple-negative breast cancers (TNBC) are characterized by the absence of estrogen, progesterone, and ERBB2 receptors, and are specifically identified as estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2). TNBC accounts for 12%–17% of all breast cancers.2 Sandhu et al. revealed a considerably greater prevalence of TNBC in India than in Western populations. Approximately one in three women diagnosed with breast cancer in India was found to have triple-negative disease.\n\nTriple-Negative Breast Cancer exhibits unique clinical and pathologic features, is highly aggressive, and has a relatively poor prognosis and clinical outcome.3 Currently, there is no recognized targeted treatment for TNBC. The primary treatment options for TNBC involve chemotherapy utilizing anthracyclines, taxanes, and/or platinum compounds as the major treatment modalities. A significant proportion of TNBC patients fail to attain Pathological Complete Response (pCR) with standard chemotherapy, prompting concerns about the effectiveness and safety of the chosen chemotherapy.4 A better understanding of the pathological mechanisms of TNBC onset and progression and the molecular interactions underlying the etiology of the condition can help improve the prophylaxis and design of novel targeted treatment against this cancer type.5\n\nGene expression profiling can be invaluable for detecting transcriptional variations between normal and malignant cells and can be extensively used to study gene phenotype associations in breast neoplasms.6 Protein interaction networks potentially signify patterns in network connectivity between proteins, which can differ between breast cancer subtypes.7 Phytochemicals are natural, non-toxic compounds found in plants that possess disease-protective or preventive properties.8 They modulate the molecular pathways associated with cancer growth and progression.9\n\nThe present study aimed to identify a novel therapeutic target protein for TNBC by integrating differential gene expression studies with protein-protein interactions and network topology analysis. Subsequently, phytochemicals with reported anti-breast cancer activities will be subjected to virtual screening by molecular docking against the identified novel target. To validate these findings, Molecular Mechanics with Generalised Born Surface Area solvation and Molecular Dynamics simulations were performed. Based on their binding affinity to the target protein, novel therapeutic phytochemical lead molecules with anti-TNBC activity were identified.\n\n\nMethod\n\nA thorough literature mining effort encompassing all eligible studies on gene expression in TNBC was conducted. The search involved querying the Gene Expression Omnibus (GEO) datasets. Gene expression profiling was performed using GEO2R to identify significantly upregulated genes. Figure 1 presents an overview of the methodology.\n\nDuring the literature mining process, a microarray dataset was obtained from the NCBI GEO repository using the accession number GSE45498 annotated in the GPL16299 platform. This dataset encompasses 40 samples from healthy normal tissues, 160 from individuals with cancer, and 54 from metastatic cases. NGS datasets were obtained from the NCBI GEO repository using accession number GSE214101 annotated in the GPL20301 platform. This dataset included 24 samples derived from the MDA-MB-231 and MDA-MB-436 cell lines. Gene expression profiling values underwent log (base2) transformation and percentage shift normalization was applied. To assess the differences in gene expression between normal and diseased samples, the fold change for each gene was individually calculated. A threshold of 1.25-fold change was used to categorize genes as being upregulated. Gene expression profiling followed the protocol reported previously.10\n\nThe selected genes were subjected to the Bisogenet plug-in of Cytoscape to identify protein-protein interactions of all genes differentially regulated in TNBC. STRING is an open-source bioinformatics platform integrated in Cytoscape, designed for the study of both predicted and known protein-protein interactions. This database gathers, evaluates, and integrates information on protein-protein interactions from all publicly available sources. Additionally, it augments these data with computational predictions.11 These interactions encompass both indirect (functional) and direct (physical) associations.12 The genes were uploaded and a string network was built. Molecular Complex Detection (MCODE) detects Protein-Protein Interactions subnetworks and highly interconnected clusters within the PPI network.13 PPI networks were broken down into top-ranked dense cliques (sub-clusters) using the MCODE plugin. The top-ranked dense clique was selected for further analysis.\n\nPhytochemicals are naturally occurring biologically active chemical compounds found in plants that serve as medicinal ingredients and nutrients, offering health benefits to humans.14 Many natural products and their analogs have been identified as potent anticancer agents and the anticancer properties of various plants and phytochemicals.15 Phytochemicals were identified through a systematic literature search indicating anti-breast cancer activity were selected, and their 3D structures in SDF format were retrieved from PubChem database. Subsequently, phytochemicals that did not conform to Lipinski’s rule of five were excluded, and the remaining compounds were subjected to further analyses.\n\nUnderstanding the fundamental principles governing how protein receptors recognize, interact, and form associations with molecular substrates and inhibitors is crucial for drug discovery. PyRx v0.8 software16 with an inbuilt AutoDock Vina 1.2.517 for molecular docking was used to scan phytochemicals conforming to Lipinski’s rule of 5. AutoDock Vina uses a semi-empirical free-energy force field to predict the binding free energies of small molecules to macromolecular targets.\n\nThe human Androgen Receptor (PDB ID: 1E3G) was sourced from the RCSB Protein Data Bank. Initially, the protein structure underwent a curation process to remove any crystallographic water molecules and heteroatoms that might interfere with docking simulations. Subsequently, energy minimization was performed using UCSF Chimera vs 1.54 (https://www.cgl.ucsf.edu/chimera/) to optimize the geometry of the protein. The steepest descent algorithm was applied for 100 steps, which is a common approach to relieve steric clashes and achieve a more stable conformation. Partial charges were then assigned to the protein using the AMBER ff14SB force field, which is well known for accurately modeling protein dynamics and interactions. The co-crystallized ligand metribolone (R18) was used as the control, and the ligands were docked at its active site.\n\nThe development of high-quality in silico ADMET models will enable compound efficacy and druggability features to be optimized concurrently, thereby improving the overall quality of drug candidates.18 ProTox-II was used to experimentally validate the chemical toxicity and their combination. It uses machine learning models, the most common features, pharmacophore-based, fragment propensities, and chemical similarity to forecast different toxicity endpoints.19 Based on the virtual screening results, the top ten phytochemical compounds were chosen for ADMET analysis.\n\nInduced fit docking was carried out using Schrodinger vs. 2020.3, which takes into account the flexibility of both the protein receptor and ligand, allowing for conformational changes to occur upon binding. The energy-minimized ligands were saved in PDB format for compatibility with the Schrodinger software, and the partial charges of the ligands were assigned, such as Gasteiger charges, which estimate the distribution of charges on the molecule based on its structure. Similarly, the protein charges may also be assigned using OPLS_2005 force fields to accurately capture its electrostatic properties. The grid box is a crucial parameter in docking simulations, as it defines the search space where the ligand can orient itself around the protein receptor. The dimensions of the grid box are typically specified in terms of the number of grid points along each axis (nx, ny, nz) and the grid spacing (Å) around the binding cavity residues LEU701, LEU707, MET742, MET745, ARG752, MET780, MET787, ALA748, LEU880, LEU873, PHE876, MET895, ILE899, THR877, GLN774, PHE764, LEU746, GLY708, GLN711, TRP741, ASN705. The dimensions were set to (58, 64, and 52 Å), providing a sufficient volume to explore potential binding modes of the ligand within the protein’s active site with a charge cutoff polarity set for a charge cutoff of 0.25 Å.\n\nMolecular dynamics (MD) simulations were conducted for the docked complex of the human Androgen Receptor with the best-docked molecule, employing Schrodinger Desmond 2020.1.20 The OPLS-2005 force field,21 along with an explicit solvent model using SPC water molecules,22 were employed in this system. The simulation was performed in a periodic boundary solvation box with dimensions of 10 × 10 × 10 Å. To neutralize the charge, Na+ ions were added, and a 0.15 M NaCl solution was added to mimic the physiological environment. The initial equilibration was carried out using an NVT ensemble for 10 ns to allow the system to relax over the protein-ligand complexes. Subsequently, a short run of equilibration and minimization was conducted using an NPT ensemble for 12 ns. The NPT ensemble utilized the Nose-Hoover chain coupling scheme23 with a temperature set at 37 °C, relaxation time of 1.0 ps, and pressure maintained at 1 bar in all simulations. A time step of 2 fs was used.\n\nPressure control was achieved using the Martyna-Tuckerman-Klein chain coupling scheme24 with a relaxation time of 2 ps. The long-range electrostatic interactions were calculated using the particle mesh Ewald method,25 and the Coulomb interaction radius was fixed at 9 Å. A RESPA integrator with a time step of 2 fs was used for each trajectory to calculate the bonded forces. The final production run was extended for 100 ns for the Human Androgen Receptor with the best-docked molecule complex. To track the stability of the MD simulations, a variety of parameters were computed, including the number of hydrogen bonds, radius of gyration (Rg), root-mean-square fluctuation (RMSF), and root-mean-square deviation (RMSD).\n\nMolecular Mechanics Generalized Born Surface Area (MM-GBSA) approaches are less computationally intensive than biochemical free energy methods and more precise than most molecular docking scoring systems. This method is useful for predicting the binding free energy in molecular systems. MM-GBSA is a useful technique for comprehending the impact of mutations on large biomolecular systems.26 Biomolecular research has been utilized in investigations of protein folding, protein-ligand binding, protein-protein interactions etc.27\n\nThe MM-GBSA approach was used to determine the binding free energies of the ligand-protein complexes. The MM-GBSA binding free energy was computed using the Python script thermal mmgbsa.py in the simulation trajectory with the VSGB solvation model and OPLS5 force field over the last 50 frames with a 1 step sampling size. The binding free energy of MM-GBSA (kcal/mol) was calculated using the additivity principle, wherein the differences in free energies, GBSA solvation energies, and surface area energies of ligand-protein complexes compared to their respective total energies of them individually were calculated.\n\n\nResults\n\nGene expression in TNBC and normal microarray datasets was compared to assess the underlying molecular pathways driving TNBC, and further network analysis was performed. Boolean operators and relevant filters were used to filter the microarray datasets using the GEO2R. The Benjamini-Hochberg-Yekutieli approach was used to adjust the P-value for the DEGs, and only the top 10% of the upregulated genes (P-value < 0.05) were selected. Tables 1 and 2 display the list of elevated genes with LogFC > 1.25 and P-value < 0.05 in dataset GSE45498 and GSE214101, respectively.\n\nThe STRING tool was used to identify potential connections between DEGs in different tissues.12 To build PPI networks, active interaction sources such as databases, co-expression, text mining, experiments, and species restricted to “Homo sapiens” were used, along with an interaction score greater than 0.4. The PPI network was displayed using Cytoscape v3.6.1 software as depicted in Figure 2.\n\nThe MCode plugin was employed to identify the highly linked regions inside the PPI network, while the CentiScape plugin was utilized to calculate the network topology parameters. Using degree and betweenness as the primary parameters, hub genes were identified. A complete set of algorithms, called CentiScape, was used to analyze the centrality of the network nodes. It can calculate multiple centralities for weighted, directed, and undirected networks.28 The human Androgen Receptor was determined to be an appropriate hub gene in the protein-protein interaction network consisting of DEG genes.\n\nThe human Androgen Receptor (hAR), covering the C-terminal amino acid residues (1E3G) with the co-crystallized ligand metribolone (R18), consists of 263 amino acid residues arranged in a three-layered α-helical sandwich structure. The ligand-binding pocket is located within the hydrophobic cavity formed by helices. A total of 1358 compounds were initially identified through systematic literature search, and their structures were retrieved from the PubChem database. Of these, only 543 compounds met the criteria outlined by Lipinski’s rule of five. These 543 compounds were then selected for the initial virtual screening against human Androgen Receptor using PyRx, and their binding affinities were tabulated29 (refer to extended data Table S1). The top 50 ranked compounds were subjected to ADMET analysis on the ProTox II server. Only the top 10 ranked compounds that showed favorable binding affinity towards hAR based on their docking interaction and ideal ADMET properties were chosen for further analysis. The initial docking results and ADMET properties are shown in extended data.\n\nMolecular interaction studies of the binding cavity of the human Androgen Receptor and molecules are listed in extended data This was compared with the co-crystallized ligand associated with hAR protein R18 and analyzed by Schrodinger-induced fit docking. The ligand 2-hydroxynaringenin demonstrated high affinity for flexible residues within the binding pocket of the Human Androgen receptor protein. The calculated free energy of binding (ΔG) was determined to be -8.59 kcal/mol, indicating a strong binding interaction. While couple of other molecules 8-Prenyldaidzein and 5-Hydroxy-7-acetoxy-8-methoxyflavone also exhibited significant binding with HAR having ΔG = -8.54 kcal/mol and -8.26 kcal/mol, respectively. The highest affinity with a low negative binding energy was observed for 2-hydroxynaringenin, where the ligand formed conventional hydrogen bonds with Leu704, Asn705, Gln711, Met745, Arg752, and Thr877. Leu707, Met780, Leu873, and Phe876 were found to be involved in pi-alkyl and alkyl interactions with the 2-Hydroxynaringenin ligand. The binding energies of 2-Hydroxynaringenin and protein-ligand interactions are displayed in Figure 4 and the binding energies of other molecules are depicted in extended data.\n\nMolecular dynamics simulation (MD) investigations were performed to ascertain the convergence and stability of 1E3G-Apo (no ligand hAR protein), 1E3G+R18 (R18 co-crystallized ligand) and 1E3G+2-Hydroxynaringenin complexes. When comparing the root mean square deviation (RMSD) measurements, the 100 ns simulation showed a stable conformation. The Apo protein’s Cα-backbone’s RMSD showed a 3.0 Å divergence (Figure 5A). While 1E3G+R18 and 1E3G+2-Hydroxynaringenin both showed 2.9 Å, the overall RMSD is shown to be 2.9 Å (Figure 5A).\n\nThe root mean square fluctuations (RMSF) plot of the 1E3G+2-Hydroxynaringenin complex protein revealed notable variations at residues 60–70, 110–120, and 180–185, which may have been caused by the residues’ increased flexibility. The rest of the residues fluctuated less during the course of the 100 ns simulation (Figure 5B). Radius of gyration (Rg) in this study, 1E3G Cα-backbone bound to Apo protein displayed increment of Rg values indicating lesser compactness while stable Rg was observed from 20.2 to 20.3 Å in 1E3G+R18 (Figure 5C). The number of hydrogen bonds was significantly different between 1E3G+2-Hydroxynaringenin, throughout the simulation time of 100 ns (Figure 5D). The average number of hydrogen bonds observed in 1E3G+2-Hydroxynaringenin was two on average in MD simulation studies (Figure 5D, red color).\n\nThe binding free energy and other contributing energies in the form of MM-GBSA were found for HAR+2-hydroxynaringenin by using the MD simulation trajectory. According to results (Table 4), the simulated complexes’ stability was primarily attributed to ΔGbindCoulomb, ΔGbindvdW, and ΔGbindLipo, whereas ΔGbindCovalent and ΔGbindSolvGB contributed to the corresponding complexes’ instability.\n\n\nDiscussion\n\nThe integrated analysis of gene expression and protein-protein interactions (PPI) would help to identify candidates that could serve as therapeutic targets. In this study, we compared TNBC datasets to normal datasets to assess the underlying molecular pathways that drive TNBC. Differential gene expression profiling of the selected datasets using the Benjamini-Hochberg-Yekutieli approach was used to adjust the P-value, which controls the rate of false discovery under positive dependence assumptions. Then, using STRING, which incorporates both known and anticipated PPIs, the protein-protein interactions between the previously mentioned genes were investigated using Cytoscape. CentiScape was used to analyze the centrality of network nodes, and the Human Androgen Receptor was determined to be an appropriate hub gene in the protein-protein interaction network consisting of DEG genes.\n\nThe Androgen Receptor (AR) pathway is becoming a viable therapeutic target in breast cancer. 12-55% of TNBC cases, which provides a chance for targeted treatment. The “Luminal AR (LAR)” molecular subtype of TNBC is where AR is most prevalent. The LAR subtype exhibits the highest amount of AR expression amongst the many molecular subtypes of TNBC in which it is present. All AR+ TNBC primary tumors that were evaluated showed nuclear localization of AR, a sign of transcriptionally active receptors. Many investigations have shown that AR expression in breast cancer, particularly in the TNBC subtype, has been linked to an overall better outcome. Considering that > 70% of AR expression is consistent between primary and metastatic breast cancers, AR may be a novel diagnostic and therapeutic target for patients with AR-positive breast cancer. In luminal mammary carcinomas, a high percentage of cases express androgen receptors (AR), and the ratio of AR to estrogen receptors (ER) or progesterone receptors (PR) is considered a potential prognostic factor. However, in estrogen receptor-negative (ER-) tumors, AR expression is associated with a poorer prognosis. Androgen receptor (AR) expression has demonstrated predictive value for potential response to adjuvant hormonal therapy in estrogen receptor-positive (ER+) breast cancers. Additionally, AR expression has been associated with predicting responses to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). The role of the AR is shown in Figure 3.\n\nThe human Androgen Receptor (hAR), which has 920 amino acid residues, was identified as the primary therapeutic target for triple-negative breast cancer. The 3D crystal of human AR retrieved from the Protein Data Bank (PDB ID 1E3G) is a partial structure covering the C-terminal amino acid residues 658-920. This region encompasses the nuclear receptor ligand-binding domain (NR LBD) of hAR. It consists of 263 amino acid residues, arranged in a three-layered α-helical sandwich structure. The ligand-binding pocket is located within the hydrophobic cavity formed by helices. Virtual screening of 543 ligands against human AR was performed using PyRx at the co-crystallized ligand-binding site. The top 10 ranked compounds that showed favorable binding affinity towards hAR and ideal ADMET properties were chosen for induced fit docking.\n\nUnlike rigid docking, induced fit docking treats the ligand and protein as typically flexible entities allowing for conformational changes to occur upon binding. The ligand 2-hydroxynaringenin demonstrated a high affinity for the flexible residues within the binding pocket of hAR, with an interaction binding energy of-8.59 kcal/mol with six conventional hydrogen bonds, indicating a strong binding interaction. Interestingly, the interaction binding energy of the hAR protein with R18 was observed to be -7.8 kcal/mol and only one conventional hydrogen bond formed between R18 and Arg752 (Figure 4). No other potential interactions were observed, except for van der Waal’s instructions. For both 2-Hydroxynaringenin and R18, it was observed that Arg752 is the key residue for ligand binding and could play an active role in protein function.\n\nMolecular dynamics (MD) simulation studies of 100 ns showed stable conformations with 1E3G+2-Hydroxynaringenin complexes. The RMSD of the Cα-backbone of the Apo protein exhibited a deviation of 3.0 Å. While 1E3G+R18 exhibited 2.9 Å and simlarly 1E3G+2-Hydroxynaringenin also exhibited the total RMSD is depicted to be 2.9 Å (Figure 5A). All RMSD values were below the acceptable range of 3 Å. Stable RMSD plots of apo-1E3G, 1E3G+R18 and 1E3G+2-Hydroxynaringenin were observed to be less than 3 Å. Therefore, it can be suggested that apo-1E3G, 1E3G+R18 and 1E3G+2-Hydroxynaringenin complexes are well converged and equilibrated.\n\nThe RMSF of the 1E3G+2-Hydroxynaringenin complex protein exhibited notable fluctuation spikes at residues 60–70, 110–120, and 180–185, which may have been brought on by the residues’ increased flexibility. During the course of the 100 ns simulation, the remaining residues fluctuated less. A more rigid conformation with fewer fluctuations was observed in the Apo-protein and 1E3G+R18 complex. Therefore, from the RMSF plots, it can be suggested that the structures of 1E3G+2-Hydroxynaringenin are more flexible during simulation in ligand-bound conformations. The radius of gyration (Rg) is a measure of protein compactness. Lowering and stable of radius of gyration (Rg) from 20.0 to 20.02 Å in 1E3G+2-Hydroxynaringenin was observed. The quantity of hydrogen bonds forming between the ligand and protein indicates a strong connection and stability of the complex. Over the course of the 100 ns simulation, there was a considerable difference in the amount of hydrogen bonds between 1E3G+2-Hydroxynaringenin (Figure 5D). The average number of hydrogen bonds observed in 1E3G+2-Hydroxynaringenin was two on average in MD simulation studies (Figure 5D, red).\n\nUsing the MD simulation trajectory, the binding free energy and additional contributing energies in the form of MM-GBSA were found for HAR+2-hydroxynaringenin. The findings (Table 4) show that ΔGbindCoulomb, ΔGbindvdW, and ΔGbindLipo were the main contributors to ΔGbind in the simulated complexes’ stability, whereas ΔGbindCovalent and ΔGbindSolvGB were responsible for the corresponding complexes’ instability. HAR+2-hydroxynaringenin complex showed significantly higher binding free energies. The capacity of 2-hydroxynaringenin to bind to the chosen protein efficiently and form stable protein-ligand complexes was demonstrated by these data, which further validated the compound’s potential.\n\n\nConclusion\n\nIn recent years, bioinformatic analysis has become essential for studying the pathogenesis of human diseases. Differential gene expression studies, protein–protein interactions, and network topology analyses were performed. The current study identified the human Androgen Receptor (AR) as a potential drug target to combat triple-negative breast cancer (TNBC). This was concluded based on gene expression profiling, protein-protein interaction, and network topology analysis. The specific role of the Androgen Receptor in breast cancer growth and progression remains uncertain, although the AR is expressed in approximately 77% of all breast cancers, even higher than Estrogen Receptors (ERs).31 A more luminal, well-differentiated, and less aggressive tumor may be indicated by high expression of Androgen Receptor in breast cancer, which could improve prognosis.32 AR inhibition tends to be well-tolerated, and patients with TNBC may benefit from it when paired with other medications, as its toxicity is much lower than that of chemotherapy. Combinations involving mTOR inhibitors, EGFR and other ErbB inhibitors, PIK3 inhibitors, anti-PDL1 antibodies, paclitaxel, and other chemotherapeutic drugs are supported by preclinical results. Randomized clinical trials would be required to ascertain the clinical utility of AR inhibitors.33–35\n\nFlavonoids are a class of natural compounds found in various fruits, vegetables, and plants and have been extensively studied for their potential therapeutic effects, including their ability to combat cancer. Naringenin, specifically categorized as a flavanone, is a flavonoid present in grapefruit and tomatoes, among other dietary sources.36 The antioxidant and anti-inflammatory properties of naringenin have led to its exploration for various potential use in the pharmaceutical industry.37\n\nThe current study identified the human Androgen Receptor as a potential candidate drug target to combat TNBC and recognized 2-hydroxynaringenin as a potential lead molecule. The in vitro and in vivo efficacies of 2-hydroxynaringenin require further investigation. Safety, pharmacokinetics, and pharmacodynamics tests need to be performed to further develop hydroxynaringenin for clinical use.",
"appendix": "Data availability statement\n\n\n\n1. GEO DATASET 1 - Accession number- GSE45498 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45498\n\nPlatform–GPL16299\n\n2. GEO DATASET 2 - Accession number- GSE214101 https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE214101\n\nSupplementary data\n\n\n\n1. Figshare: Molecular docking and MD simulation approach to identify potential phytochemical lead molecule against triple negative breast cancer - Supplementary Figures.docx - DOI: 10.6084/m9.figshare.26967880.v1 38\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n2. Figshare: Molecular docking and MD simulation approach to identify potential phytochemical lead molecule against triple negative breast cancer - Supplementary Table.docx - DOI: 10.6084/m9.figshare.26967733.v1 39\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\nArnold M, Morgan E, Rumgay H, et al.: Current and future burden of breast cancer: Global statistics for 2020 and 2040. The Breast. 2022 Dec 1; 66: 15–23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBergin AR, Loi S: Triple-negative breast cancer: recent treatment advances. F1000Research. 2019; 8: 1342. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKalimutho M, Parsons K, Mittal D, et al.: Targeted therapies for triple-negative breast cancer: combating a stubborn disease. Trends in Pharmacological Sciences. 2015 Dec 1; 36(12): 822–846. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nTung NM, Garber JE, Torous V, et al.: Prevalence and predictors of androgen receptor (AR) and programmed death-ligand 1 (PD-L1) expression in BRCA1-associated and sporadic triple negative breast cancer (TNBC).\n\nMuralidharan S, Velanganni AA, Shanmugam K: Inhibition of Breast Cancer Proteins by the Flavonoid Naringenin and its Derivative: A Molecular Docking Study. Journal of Natural Remedies. 2022 Jan 22; 51–64. Publisher Full Text\n\nZhao Z, Jin G, Ge Y, et al.: Naringenin inhibits migration of breast cancer cells via inflammatory and apoptosis cell signaling pathways. Inflammopharmacology. 2019 Oct; 27: 1021–1036. PubMed Abstract | Publisher Full Text\n\nSankaranarayanan P, John DGD, Abhinand PA, et al.: Molecular docking and MD simulation approach to identify potential phytochemical lead molecule against triple negative breast cancer - Supplementary Figures.docx. figshare. 2024. 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}
|
[
{
"id": "335168",
"date": "10 Dec 2024",
"name": "Shiek S S J Ahmed",
"expertise": [
"Reviewer Expertise Neuroscience",
"Cancer research",
"immunoinformatic",
"systems biology",
"NGS",
"artificial intelligence",
"omics research",
"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\nThis manuscript provides valuable insights into drug discovery in the field of oncology. The authors have done excellent work in exploring breast cancer treatment by utilizing efficient computational methods such as differential gene expression, protein network, molecular docking, molecular dynamics simulations, and MM-GBSA. The study aims to identify potential lead compounds against a candidate target for triple-negative breast cancer. However, the following issues need to be addressed before indexing.\n1. Abstract needs to reframed { (#Note: Can be re-constructed based to authors preference) Example: Background Triple-negative breast cancers (TNBC) are defined as tumors that lack the expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It exhibits unique clinical and pathological features, high aggressiveness, and has a relatively poor prognosis and clinical outcome. Objective To identify a novel drug target protein against TNBC and potential phytochemical lead molecules against the identified targets. Methods In this study, we retrieved TNBC samples from NGS and microarray datasets in the Gene Expression Omnibus database. We employed a combination of differential gene expression studies, protein-protein interaction analysis, and network topology investigation to identify the target protein. Additionally, the molecular docking and molecular dynamics (MD) simulation studies followed by Molecular Mechanics with Generalised Born Surface Area salvation was used to identify potential lead molecule. Results The upregulated genes with LogFC > 1.25 and P-value < 0.05 from the TNBC gene expression dataset were identified. Androgen receptor (AR) was found to be an appropriate hub target in the protein-protein interaction network. Phytochemicals that inhibit breast cancer target were retrieved from the PubChem database and virtual screening was performed using PyRx against the AR protein. Thereby, the AR was found to be the target protein and 2-hydroxynaringenin was discovered to be a possible phytochemical lead molecule for combating TNBC. Moreover, the AR and the 2-hydroxynaringenin complex showed structural stability and higher binding affinity through molecular dynamics and MM-GBSA studies. Conclusion AR was identified as a hub protein that is highly expressed in breast cancer and 2-hydroxynaringenin efficacy of counter TNBC requires further investigation both in vitro and in vivo.} please refer to following link for more details https://f1000research.s3.amazonaws.com/linked/695061.155657-F1000_review_1_.docx\n2. Please do not use scientific term multiple times. rather use the abbreviation.\n\n3. In the methodology section, the calculation of MD trajectories is unclear. Was the Desmond plug-in employed, or manually? Additionally, there appears to be a contrast between the described MD simulation methodology and the reported results. The MD simulation results might have been obtained using GROMACS rather than Desmond. This assumption arises because Desmond typically calculates parameters such as the Rg and intramolecular hydrogen bonds (intraHB) for the ligand's extendness and internal hydrogen bonding, but not for the entire complex.\n4. The authors should clearly define the criteria used for selecting those two datasets (gene expression) in the methodology section. The datasets seems heterogeneous one consists of human sample (expression array) while the other consists of cell line samples (RNA-sequencing). How the authors address and account for batch effects arising from these differences?\n4a. The basis for the adopting the LogFC > 1.25 as a threshold while in gene expression analysis should be explained\n5. How the 2D interaction of protein and ligand was visualized after docking.\n6. In Fig. 5B, the RMSF does not cover the entire protein (263 amino acids).\n7. Some important references are missing in the discussion section, particularly in AR association with Breast cancer (second paragraph).\n8. In Fig 2, highlighting the hub target protein or constructing the sub-network by centering AR would enhance visualization and helpful for the new readers to understand.\n\n9. The following sentence needs referencing “All RMSD values were below the acceptable range of 3Å”.\n10. The interpretation of the MM-GBSA results needs to be clarified. Specifically, the outcomes of the MM-GBSA analysis comparing the test and control compounds should be explained in detail.\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?\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": []
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https://f1000research.com/articles/13-1271
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https://f1000research.com/articles/13-1269/v1
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24 Oct 24
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{
"type": "Research Article",
"title": "Prevalence and risk factors of Acinetobacter baumannii infection in Pediatric Intensive Care Unit at Thammasat University Hospital",
"authors": [
"Pornumpa Bunjoungmanee",
"Kornkamon Rattanapan",
"Yamonbhorn Neamkul",
"Auchara Tangsathapornpong",
"Narissara Mungkornkaew",
"Prapasri Kulalert",
"Kornkamon Rattanapan",
"Yamonbhorn Neamkul",
"Auchara Tangsathapornpong",
"Narissara Mungkornkaew",
"Prapasri Kulalert"
],
"abstract": "Background\nAcinetobacter baumannii infection (ABI) is a concerning worldwide public health matter with high levels of morbidity and mortality, particularly in critically ill patients. This study aims to assess the prevalence, risk factors, and clinical outcomes of ABI in the pediatric intensive care unit (PICU) setting.\n\nMethods A retrospective review was performed on pediatric patients admitted to the PICU over an 8-year period. Demographic characteristics, infection risk factors, and clinical outcomes were compared and analyzed between patients with ABI, determined to be the case group, and patients without ABI, determined to be the control group. The study also assessed the prevalence of ABI and its antimicrobial resistance profile.\n\nResults Between June 2014 and May 2022, a total of 82 cases of ABI were identified, resulting in an overall prevalence of 5.02%. After applying the exclusion criteria, 12 cases were excluded. Consequently, 70 ABI cases in total and 140 cases in a control group were included in the study. Multivariable conditional logistic regression analysis identified chronic respiratory disease, mechanical ventilation lasting 3 days or more, and the use of piperacillin/tazobactam within the last 2 weeks as independent risk factors associated with ABI. The rate of carbapenem-resistant A. baumannii (CRAB) was notably high at 93.22%. Cases of ABI were associated with higher mortality rates and prolonged hospitalization compared to non-ABI cases.\n\nConclusion ABI remains a critical pathogen in the PICU. The presence of chronic respiratory disease, use of mechanical ventilation for at least three days, and a history of receiving piperacillin/tazobactam within the last 2 weeks are significant risk factors for ABI. The high level of antibiotic resistance, especially to carbapenems, highlights the emphasis for more stringent infection control practices and the creation of novel antimicrobial therapies.",
"keywords": [
"Acinetobacter baumannii infection (ABI)",
"pediatric intensive care unit (PICU)",
"carbapenem-resistant Acinetobacter baumannii (CRAB)"
],
"content": "Introduction\n\nAcinetobacter baumannii causes significant problematic issues in healthcare-associated infections (HAIs). A. baumannii usually causes various infections, including sepsis, pneumonia, meningitis, urinary tract infection, skin and soft tissue infection.1–3 The critical factors contributing to the global challenge of A. baumannii in healthcare settings include the pathogen’s capacity to rapidly evolve mechanisms of drug resistance, its ability to persist in the environment, leading to widespread transmission, and the high morbidity and mortality rates of infections.4–7 The emergence of pan-antibiotic-resistant A. baumannii and the lack of effective treatments have led to its classification as a serious public health concern. A. baumannii has been designated as an urgent threat, necessitating the development of enhanced therapeutic strategies.8,9\n\nPrevious studies demonstrated the emergence of A. baumannii infections (ABI) with extremely high rates of carbapenem resistance among adults in Thailand, ranging between 70% to 80%, and mortality rates exceeding 60%.10–12 Consequently, ABI is estimated to result in over 15,000 deaths each year.13 However, there is limited research on A. baumannii in pediatric populations, particularly within intensive care unit (ICU) settings. This study aimed to identify the prevalence and potential risk factors of ABI, along with the outcomes in critically ill children.\n\n\nMethods\n\nThis research study received approval from the Human Research Ethics Committee of Thammasat University (Medicine), in accordance with international guidelines, including the Declaration of Helsinki, The Belmont Report, CIOMS Guidelines, and the International Conference on Harmonization-Good Clinical Practice (ICH-GCP). The approval number was MTU-EC-PE-0-125/65 on September 2, 2022. Data collection commenced following the Ethics Committee’s authorization. Informed consent was waived due to the retrospective nature of the study. Data was then collected through the review of patient medical records without any direct participant contact or intervention.\n\nThe study was a retrospective case-control study of pediatric patients under the age of 15 years at Thammasat University Hospital, a tertiary care facility with an 8-bed pediatric intensive care unit (PICU), from June 2014 and May 2022. All strains of A. baumannii were classified as causative agents of HAIs based on identification in the microbiology laboratory database, meeting the established criteria for significant pathogens.\n\nTo identify cases of A. baumannii from PICU, we reviewed culture results from specimens obtained throughout the patients’ hospitalizations. Cases were defined as patients who acquired ABI 48 hours or more following admission to the PICU. Controls were defined as patients admitted to the PICU without ABI. Seventy cases and 140 controls were randomly matched in a 1: 2 ratio. Controls were randomly selected from the same month as cases admitted to the PICU. Patients with A. baumannii identified within the first 48 hours of PICU admission, a PICU stay of less than 48 hours, or incomplete records were excluded.\n\nA. baumannii was identified and confirmed from the sample using standard microbiological techniques. The susceptibility of the isolates was assessed by determining the minimum inhibitory concentrations following the Clinical and Laboratory Standards Institute (CLSI) guidelines,14 using the VITEK2 compact system (bioMérieux, France). Colistin susceptibility was assessed using broth microdilution in accordance with CLSI14 and The European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.15 Multidrug-resistant A. baumannii (MDRAB) is defined as isolates exhibiting resistance to at least one agent from three or more antimicrobial classes. Extensively drug-resistant A. baumannii (XDRAB) refers to isolates that demonstrate susceptibility exclusively to tigecycline and colistin, while exhibiting resistance to all other antibiotic classes. Carbapenem-resistant A. baumannii (CRAB) is characterized by nonsusceptibility involving at least one of three agents within the carbapenem class.16\n\nData collection\n\nThis study utilized a systemic computer-assisted database search to obtain retrospective data on patients discharged from the PICU. Information on demographics, clinical outcomes, and microbiological data were gathered from medical and laboratory records.\n\nData analysis\n\nCategorical variables were presented as frequencies and percentages, whereas continuous variables were given as mean and standard deviation. Non-normally distributed data was expressed as median and interquartile range (IQR). The Rank-Sum test was utilized for non-normally distributed continuous variables and the t-test was applied for comparing normally distributed continuous variable. Chi-square or Fisher’s exact test was utilized to compare categorical data as appropriate. The identification of independent factors associated with ABI was analyzed using univariable and multivariable conditional logistic regression, with statistical significance set at p < 0.05. Statistical analysis was done using STATA version 17.0.\n\n\nResults\n\nThroughout the 8-year duration of the study, a total of 1,635 PICU admission were recorded. Eighty-two cases of ABI were identified giving the overall prevalence of 5.02%. Twelve cases were excluded (7 cases with A. baumannii identified within the first 48 hours, and 5 cases had incomplete medical data). The remaining ABI were 70 cases. Among them, the percentage of CRAB reached 93.22%. One hundred forty patients with negative A. baumannii specimens who met the matching criteria were included as controls.\n\nUpon analyzing the annual prevalence of ABI in the PICU, the rate exhibited a fluctuating pattern from 2014 to 2022. From 2014 to 2016, the rate remained stable at 3.00, followed by a noticeable increase in 2017 to 4.14. The prevalence peaked in 2018 at 5.94, before slightly declining to 5.22 in 2019. A more significant decrease was observed in 2020 and 2021, with rates dropping to 3.97 and 3.78, respectively. However, in 2022, the prevalence rebounded to 5.4, approaching the 2018 peak. This overall trend suggests periodic fluctuations in ABI, with notable peaks occurring in 2018 and 2022.\n\nPatients’ clinical characteristics in each group are shown in Table 1. The ABI cases exhibited a younger age and a greater frequency of comorbidities, referral from another hospital, prior hospitalizations, antibiotic use, mechanical ventilation, and central/arterial line placements. Additionally, the use of broad-spectrum antibiotics and lengthy hospitalization prior to the onset of ABI tended to be more frequent in this group. Patients with ABI experienced prolonged hospitalization after the onset of infection and demonstrated an increasing mortality rate compared to patients without ABI.\n\n* Statistically significant.\n\na Bronchopulmonary dysplasia (BPD), and asthma.\n\nb Hematologic malignancy, on immunosuppressive drug, primary immunodeficiency.\n\nc Third-generation cephalosporins, beta-lactam/beta-lactamase inhibitors, aminoglycosides, and carbapenems.\n\nAmong patients with ABI, there were 28 cases (40.00%) identified as ventilator-associated pneumonia, 10 cases (14.28%) as bloodstream infections, 8 cases (11.43%) as catheter-related bloodstream infections, 5 cases (7.15%) as skin and soft tissue infections, 2 cases (2.86%) as catheter-associated urinary tract infections, 2 cases (2.86%) as ventricular shunt infections, and 15 cases (21.42%) were identified as having a combination of multiple infection types.\n\nIn our study, ABI was associated with a mortality rate of 15.71%. All fatal cases involved patients with at least one comorbidity or a history of major surgical intervention. Of these, two patients had acute leukemia, two had chronic respiratory disease, two had an underlying genetic disorder with airway anomalies, two had congenital heart disease, two had a recent car accident and had undergone major surgery in the past 10 days, and one had a brain tumor with craniotomy in the past two weeks. All cases were complicated by septic shock and multiorgan failure, resulting in fatal outcomes.\n\nCultures were obtained from 70 cases of ABI. Of these 177 isolates, 133 were from respiratory samples (75.14%), 35 were from blood (19.77%), 5 were from pus (2.83%), and 4 were from urine (2.26%). High co-resistance rates were observed for meropenem (93.22%), imipenem (92.00%), piperacillin-tazobactam (90.81%), ciprofloxacin (89.60%), ceftazidime (88.57%), amikacin (84.09%), and cefoperazone-sulbactam (81.95%). In contrast, low resistance rates were observed for tigecycline (3.21%). All the isolates were susceptible to colistin according to the EUCAST guidelines,15 while exhibiting intermediate susceptibility to colistin based on the CLSI guidelines.14 According to the criteria established by Magiorakos et al,16 most of the isolates were classified as MDRAB (n = 170, 96.05%) and 87.57% were classified as XDRAB (n = 155).\n\nFactors associated with ABI, as determined by both univariable and multivariable conditional logistic regression analysis, are presented in Table 2. In the univariable analysis, the risk factors associated with ABI included being under 12 months of age, chronic respiratory disease, congenital heart disease, and genetic disease. Furthermore, referral from another hospital, prior hospitalization within 3 months, prior antibiotic use within 3 months, and PICU stay longer than 7 days were significantly associated with ABI. Mechanical ventilation lasting 3 days or more, central line or arterial line placement, using piperacillin/tazobactam or carbapenems within the last 2 weeks significantly increased the risk of ABI.\n\n* Statistically significant.\n\na Bronchopulmonary dysplasia (BPD), and asthma.\n\nThe final multivariable conditional logistic regression analysis identified chronic respiratory disease, mechanical ventilation lasting 3 days or more, and the use of piperacillin/tazobactam within the last 2 weeks as independent factors associated with ABI.\n\n\nDiscussion\n\nA. baumannii species are emerging as a significant public health threat, frequently exhibiting multidrug resistance and being associated with high mortality rates. An analysis of data collected over eight consecutive years revealed that the overall prevalence of ABI in the PICU was approximately 5.02%. This prevalence is lower than previous studies, which ranged from 8.30% to 15.30%.17–19\n\nThe prevalence of ABI significantly declined between 2020 and 2021, a period coinciding with the global COVID-19 pandemic. Several studies have reported reductions in ABI rates during this time, with decreases ranging from 1.00% to 3.00%.20–23 This reduction is likely associated with widespread lifestyle changes and the emphasis for more stringent practices of infection control aimed at timing the transmission of SARS-CoV-2. These measures contributed to a decline in respiratory infections among children, reduced ICU admissions for non-COVID-19 cases, a reduction in hospitalization rates, and fewer pediatric patients with severe SARS-CoV-2 infections who required PICU admission.\n\nSimilar to adults, the major factors related to the emergence and spread of ABI in children, as demonstrated in previous studies, included misguided antimicrobial treatment and prior invasive procedure such as mechanical ventilation, central venous catheterization, and urinary catheters.1,24–26 Our study found that the use of piperacillin-tazobactam, prolonged mechanical ventilation for a minimum of 72 hours, and chronic respiratory disease were significantly associated with an increased risk of ABI.\n\nNowadays, where carbapenems are frequently administered, particularly for the treatment of severe cases, the selective pressure may encourage the emergence and spread of CRAB. As a result, the widespread administration of carbapenems is a potential risk factor of ABI.6,27–29 Differing from previous studies, our study identified piperacillin-tazobactam as a significant risk factor. This difference was attributed to the antibiotic prescribing practices at Thammasat University Hospital.\n\nPiperacillin-tazobactam was widely available and could be prescribed by physicians across various specialties without restriction. Conversely, the use of carbapenem was tightly regulated, requiring authorization from a pediatric infectious disease specialist prior to prescription. As a result, physicians commonly chose piperacillin-tazobactam, a broad-spectrum antibiotic with a similar efficacy profile to carbapenems, particularly for critically ill patients in the PICU. This prescribing pattern likely contributed to the observed association between piperacillin-tazobactam and an increased risk of ABI, which was statistically significant in this study.\n\nOur study is the first to identify chronic respiratory disease, including bronchopulmonary dysplasia (BPD) and asthma, as significant risk factors for ABI. In these patients, the compromised pulmonary architecture and function facilitated bacterial colonization and subsequent infection. Furthermore, these patients often had a history of recurrent hospitalizations and a potential need for mechanical ventilation, both of which contribute to an increased risk of hospital-acquired ABI. Research data in adults demonstrated that chronic obstructive pulmonary disease (COPD) was a significant risk factor for acquiring ABI.30–33 These findings underscore the significance of chronic lung conditions in predisposing individuals to ABI across different age groups.\n\nOur study demonstrated that mechanical ventilation lasting 3 days or more was an independent factor associated with ABI. Encouraging non-invasive mechanical ventilation and gradually weaning respiratory support while assessing the necessity for endotracheal intubation,34 combined with the implementation of targeted antibiotic stewardship program and the reinforcement of rigorous infection control protocols within healthcare setting,5 can reduce the hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) and substantially mitigate the risk of ABI.\n\nThe rise of CRAB poses a significant challenge to treatment, as therapeutic options become markedly constrained. These resistant strains are associated with higher morbidity and mortality rates and are increasingly recognized as among the most problematic bacterial pathogens.1,3,6,7,29,35 In our study, the prevalence of CRAB reached 93.22%. The presence of CRAB strains is frequently associated with outbreaks in hospital ICU and presents significant challenges to infection control within healthcare settings.5,36,37 To minimize the risk, carbapenems should be used judiciously, and infection control measures should be strictly implemented.\n\nThe high mortality rate associated with ABI may be related to the extent of antimicrobial resistance, the efficacy of empirical therapy, and the availability of targeted therapeutic options. The overall mortality rate in our study was 15.71%, consistent with finding from previous studies.3,28,38 However, other studies reported higher mortality rate, ranging from 28.3% to 48.65%. This variation is likely attributable to the inclusion of patients with A. baumannii sepsis, with or without septic shock, and delayed in initiating appropriate antibiotic regimens effective against A. baumannii once the infection was established.1,4,6,29,39\n\nA. baumannii is an important threat to patients of all ages, including children. Therefore, ongoing surveillance of ABI in pediatric populations and continuous assessment of effective prevention strategies for at-risk children are essential. The widespread prevalence of antibiotic-resistant A. baumannii strains, combined with the scarcity of new antimicrobial agents, restricts the available therapeutic options. Prioritizing vaccine development against A. baumannii may be regarded as a potential strategy to combat the challenge of antimicrobial resistance in this pathogen moving forward, which is currently under investigation in research studies.40–43\n\nThe study demonstrates several notable strengths. The extended study period of eight years enables a comprehensive analysis of trends in ABI over time. Focusing on the critically ill pediatric population addresses a significant knowledge gap in understanding the risk factors associated with ABI through multivariable conditional logistic regression analysis and highlights the patterns of antibiotic resistance.\n\nThe study had some limitations that should be considered. The retrospective design introduces potential biases. Additionally, being a single-center study limits the generalizability of the findings to other healthcare settings with differing patient demographics and hospital practices. Furthermore, the study lacks detailed genetic analysis, thereby limiting the depth of understanding regarding the genetic mechanisms behind antibiotic resistance.\n\n\nConclusion\n\nThis study highlights the significant burden of ABI, particularly carbapenem-resistant strains, in the PICU setting. Prolonged mechanical ventilation for at least 3 days, underlying chronic respiratory disease, and the administration of piperacillin/tazobactam contribute to a higher risk of developing ABI. The findings of our study underscore the importance of the stringent practices of infection control and antibiotic stewardship measures, alongside advocating the use of non-invasive mechanical ventilation in lieu of endotracheal intubation, which can substantially mitigate the risk of ABI. Although the study identifies key risk factors and provides valuable insights into the epidemiology of A. baumannii in the PICU, further research and enhanced infection prevention strategies are necessary to reduce morbidity and mortality related to ABI in critically ill pediatric populations.",
"appendix": "Data availability\n\nZenodo: Prevalence and risk factors of Acinetobacter baumannii infection in Pediatric Intensive Care Unit at Thammasat University Hospital.\n\nThe anonymized data sets of this project are available in the Zenado: https://doi.org/10.5281/zenodo.13921141. 44\n\nThe project contains the following underlying data:\n\n• Data patient case reviwed.xlsx\n\n• Data patient control reviewed.xlsx\n\nData are available under the term of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nZenodo: Prevalence and risk factors of Acinetobacter baumannii infection in Pediatric Intensive Care Unit at Thammasat University Hospital: DOI: https://doi.org/10.5281/zenodo.13921141. 44\n\nThe project contains the following checklist:\n\n• STROBE checklist for prevalence and risk factors of Acinetobacter baumannii infection in pediatric intensive care unit at Thammasat university hospital\n\nData are available under the term of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nAcknowledgements\n\nThe authors thank the Research Group of Pediatrics, the Faculty of Medicine, Thammasat University, for their contributions to the conceptualization and execution of the study. Appreciation is also extended to Ms. Sam Ormond for her meticulous review and editing of the manuscript’s English language.\n\n\nReferences\n\nPunpanich W, Nithitamsakun N, Treeratweeraphong V, et al.: Risk factors for carbapenem non-susceptibility and mortality in Acinetobacter baumannii bacteremia in children. Int. J. Infect. Dis. 2012; 16(11): e811–e815. Publisher Full Text\n\nKonca C, Tekin M, Geyik M: Susceptibility Patterns of Multidrug-Resistant Acinetobacter baumannii. Indian J. Pediatr. 2021; 88(2): 120–126. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZhu Y, Zhang X, Wang Y, et al.: Insight into carbapenem resistance and virulence of Acinetobacter baumannii from a children’s medical centre in eastern China. Ann. Clin. Microbiol. Antimicrob. 2022; 21(1): 47. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHong Y, Lin X, Zhang C, et al.: Initial indicators for the prognosis of Acinetobacter Baumannii bacteremia in children. BMC Infect. 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J. 2018; 52(suppl 62): PA4099.\n\nKhilnani GC, Dubey D, Hadda V, et al.: Predictors and microbiology of ventilator-associated pneumonia among patients with exacerbation of chronic obstructive pulmonary disease. Lung India. 2019; 36(6): 506. Publisher Full Text\n\nKlompas M, Branson R, Cawcutt K, et al.: Strategies to prevent ventilator-associated pneumonia, ventilator-associated events, and nonventilator hospital-acquired pneumonia in acute-care hospitals: 2022 Update. Infect. Control Hosp. Epidemiol. 2022; 43(6): 687–713. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHasan B, Perveen K, Olsen B, et al.: Emergence of carbapenem-resistant Acinetobacter baumannii in hospitals in Pakistan. J. Med. Microbiol. 2014; 63(Pt 1): 50–55. Publisher Full Text\n\nRisser C, Pottecher J, Launoy A, et al.: Management of a Major Carbapenem-Resistant Acinetobacter baumannii Outbreak in a French Intensive Care Unit While Maintaining Its Capacity Unaltered. Microorganisms. 2022; 10(4): 720. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDoughty EL, Liu H, Moran RA, et al.: Endemicity and diversification of carbapenem-resistant Acinetobacter baumannii in an intensive care unit. Lancet Reg. Health West Pac. 2023; 37: 100780. Publisher Full Text\n\nVandepitte WP, Berge J, Andersson R: Clinical outcomes of children with carbapenem-resistant Acinetobacter baumannii bacteremia. J. Med. Assoc. Thail. 2014; 97 Suppl 11: S129–S139.\n\nTaşkın E: Acinetobacter infections in pediatric intensive care unit: A single-center experience. Ümraniye Pediatri Dergisi - Journal of Umraniye Pediatrics. 2024; 4(1): 39–46. Publisher Full Text\n\nElbehiry A, Marzouk E, Moussa I, et al.: The Prevalence of Multidrug-Resistant Acinetobacter baumannii and Its Vaccination Status among Healthcare Providers. Vaccines (Basel). 2023; 11(7). Publisher Full Text\n\nTan YC, Lahiri C: Promising Acinetobacter baumannii Vaccine Candidates and Drug Targets in Recent Years. Front. Immunol. 2022; 13: 900509. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYang N, Jin X, Zhu C, et al.: Subunit vaccines for Acinetobacter baumannii. Front. Immunol. 2022; 13: 1088130.\n\nPiri-Gharaghie T, Doosti A, Mirzaei SA: Novel adjuvant nano-vaccine induced immune response against Acinetobacter baumannii. AMB Express. 2023; 13(1): 31. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBunjoungmanee P, Tangsathapornpong A, Kulalert P, et al.: Prevalence and risk factors of Acinetobacter baumannii infection in Pediatric Intensive Care Unit at Thammasat University Hospital. Zenodo. 2024."
}
|
[
{
"id": "342361",
"date": "22 Nov 2024",
"name": "Visal Moolasart",
"expertise": [
"Reviewer Expertise infectious",
"HIV EID IPC and children"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis manuscript presents a compelling message and provides valuable insights into the \"Prevalence and Risk Factors of Acinetobacter baumannii Infection in the Pediatric Intensive Care Unit at Thammasat University Hospital.\" However, there are several issues that merit further consideration.\n1. This case-control study compares the risk factors for Acinetobacter baumannii infections with those for non-Acinetobacter baumannii infections (control group). While the information provided is valuable, further consideration of several issues is necessary, such as the selection criteria and characteristics of the control group, potential confounding factors, and the robustness of the data analysis.\n\n-A study by Uwingabiye J et al reported that Acinetobacter baumannii accounted for 22.6% of infections in the ICU. In several study, the mortality rate associated with A. baumannii infections ranges from 26.5% to 91%, reaching as high as 70% for infections caused by resistant strains. These findings highlight the severity of cases involving A. baumannii.\n\n- The selection of a control group is a critical aspect of case-control study design. In this study, the control group was defined as patients with non-Acinetobacter baumannii infections, representing less severe cases with fewer underlying conditions. To address this issue, the authors might consider selecting a more appropriate control group for comparison. For example, other studies have compared children with carbapenem-resistant A. baumannii (CRAB) infections to those with carbapenem-susceptible A. baumannii (CSAB) infections, which could provide a more balanced and clinically relevant comparison.\n\nThe authors may consider matching the control group by adding specific conditions to ensure appropriate integration and analysis. This approach could help create a more balanced comparison and improve the validity of the findings.\n\n2. Case group: The Acinetobacter baumannii group is divided into two subgroups: resistant and non-resistant strains. Please consider this distinction, as several factors may differ between these subgroups and could influence the analysis and outcomes.\n3. If the authors intend to compare two groups for factor analysis, they should consider the sample size in each group to ensure sufficient statistical power and reliable results.\n4. This information demonstrated” Upon analyzing the annual prevalence of ABI in the PICU, the rate exhibited a fluctuating pattern from 2014 to 2022. From 2014 to 2016, the rate remained stable at 3.00, followed by a noticeable increase in 2017 to 4.14. The prevalence peaked in 2018 at 5.94, before slightly declining to 5.22 in 2019. A more significant decrease was observed in 2020 and 2021, with rates dropping to 3.97 and 3.78, respectively. However, in 2022, the prevalence rebounded to 5.4, approaching the 2018 peak. This overall trend suggests periodic fluctuations in ABI, with notable peaks occurring in 2018 and 2022.”\n\nThis data is interesting and valuable for integration and analysis in this study. To further enhance the manuscript, consider incorporating graphs or illustrations to better visualize the findings, along with a more in-depth discussion to provide additional context and insights.\n\n5. Please include additional information in the background section, focusing on key risk factors and reviewing relevant statistics. This will help readers better understand the context and significance of the findings.\n6. A discussion on drug resistance should also be included as part of the result and analysis. Lastly, ensure that a section on the limitations of the study is added to provide a more comprehensive view of the research.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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/13-1269
|
https://f1000research.com/articles/13-1268/v1
|
24 Oct 24
|
{
"type": "Software Tool Article",
"title": "BEpipeR: a user-friendly, flexible, and scalable data synthesis pipeline for the Biodiversity Exploratories and other research consortia",
"authors": [
"Marcel Glück",
"Oliver Bossdorf",
"Henri A. Thomassen",
"Oliver Bossdorf",
"Henri A. Thomassen"
],
"abstract": "Background Large research consortia can generate tremendous amounts of biological information, including high-resolution soil, vegetation, and climate data. While this knowledge stock holds invaluable potential for answering evolutionary and ecological questions, making these data exploitable for modelling remains a daunting task due to the many processing steps required for synthesis. This might result in many researchers to fall back to a handful of ready-to-use data sets, potentially at the expense of statistical power and scientific rigour. In a push for a more stringent approach, we introduce BEpipeR, an R pipeline that allows for the streamlined synthesis of plot-based Biodiversity Exploratories data.\n\nMethods BEpipeR was designed with flexibility and ease of use in mind. For instance, users simply choose between aggregating forest or grassland data, or a combination thereof, effectively allowing them to process any experimental plot data of this research consortium. Additionally, instead of coding, they parse most processing information in a user-friendly way through parameter sheets. Processing includes, among others, the creation of a spatially explicit plot-ID template, data wrangling, quality control, plot-wise aggregations, the calculation of derived metrics, data joining to a large composite data set, and metadata compilation.\n\nResults With BEpipeR, we provide a feature-rich pipeline that allows users to process Biodiversity Exploratories data in a flexible and reproducible way. This pipeline might serve as a starting point for aggregating the numerous data sets of this and potentially similar research consortia. In this way, it might be a primer for the construction of consortia-wide composite data sets that take full advantage of the consortia’s rich information stocks, ultimately boosting the visibility and participation of individual research projects.\n\nConclusions The BEpipeR pipeline permits the user-friendly processing and plot-wise aggregation of Biodiversity Exploratories data. With modifications, this framework may be easily adopted by other research consortia.",
"keywords": [
"Research consortia",
"large-scale long-term environmental research",
"environmental data",
"data democratization and utilization",
"reproducibility",
"R programming language",
"Biodiversity Exploratories",
"BExIS"
],
"content": "Introduction\n\nLarge-scale long-term environmental research frameworks such as LTER (Hobbie et al. 2003), TEAM (Rovero and Ahumada 2017), ForestGEO (Anderson-Teixeira et al. 2015, Davies et al. 2021), and the Biodiversity Exploratories (Fischer et al. 2010a, 2010b) are at the forefront of functional biodiversity research. These frameworks are fuelled by well-orchestrated infrastructure projects, unmatched standing scientific expertise, and high-resolution time-series data. This combination of factors allows them to answer some of the most intricate and pressing ecological questions of our time with high statistical power. For instance, they shed light on how land-use shapes biodiversity and ecosystem processes (Allan et al. 2015, Felipe-Lucia et al. 2020, Le Provost et al. 2023), how this gives rise to profound changes in community composition and network interactions (Weiner et al. 2014, Vályi et al. 2015, Blüthgen et al. 2016, Chavarria et al. 2021), and the importance of temporal and spatial heterogeneity in shaping these patterns (Kloss et al. 2011, Allan et al. 2014, Seibold et al. 2019, van Breugel et al. 2019).\n\nDue to their size and the presence of dedicated infrastructure projects, these frameworks continue to benefit from an ever-increasing stock of biological data. For instance, as of 19/03/2024, the Biodiversity Exploratories Information System (BExIS, Chamanara et al. 2021) featured more than 1500 data sets for their experimental forest and grassland plots (EPs). Arguably, while this wealth of information holds great promise for answering even highly intricate research questions, considerable effort is needed to combine these data in a way that allows for their straightforward use. While for a limited number of data sets and at the expense of reproducibility, such processing might be performed in spreadsheet editors such as LibreOffice Calc or Microsoft Excel, this approach becomes increasingly infeasible when more data are incorporated, ultimately asking for a more efficient way of processing. While this often means using programming languages such as R, Python, and Julia, not all ecologists might be used to these languages and learning one can be perceived as daunting (Baker 2017, Custer et al. 2021).\n\nUnsurprisingly, to circumvent these challenges, many research projects within these consortia might rely on a handful of data sets that allow for a straightforward and less time-consuming incorporation into their workflows. By doing so, they might leave out potential data that would have been instrumental in answering their complex scientific questions, ultimately causing a loss in statistical power. Instead, a more compelling approach would be a tool that allows for a user-friendly processing of data sets, rendering the decision between progressing fast or incorporating many data obsolete. To this end, we introduce BEpipeR, an R pipeline that allows for the synthesis of EP-level (a)biotic Biodiversity Exploratories data. To maximise its usability and ease of implementation, we purposely limited the amount of coding required. For instance, we allow users to parse most aggregation information through csv files and toggle easily between three aggregation modes (forest, grassland, or combined) that allow for the straightforward processing of data provided by this research framework.\n\nRegardless of the mode selected, BEpipeR performs the following processing: creation of a spatially explicit plot-ID template, data substitution through exact and pattern-based approaches, subsettings, resolving species aggregates issues through fallbacks, data reshaping, variables standardization, mean and median-based outlier detection, data aggregation both within and across data sets, processing and aggregation of climate data generated and extensively pre-processed by TubeDB (Wöllauer et al. 2021); in the following referred to as “BExIS’ climate tool”, normalization by repeated rarefaction, calculating alpha diversity indices, data joining to template, quality control, variables selection by variance inflation factor analyses, and the compilation of metadata from JSON metadata files. Arguably, BEpipeR has the potential to generate large composite data sets in a highly reproducible fashion (Baker 2016). As this might aid the democratization and utilization of available research data, we hope for this pipeline to become a focal point for compiling the vast amount of environmental information generated by the Biodiversity Exploratories and, potentially, similar research consortia.\n\n\nMethods\n\nBEpipeR is written in R v.4.1.1 (R Core Team 2021) and harnesses renv v.1.0.3 (Ushey and Wickham 2023) to establish an R project-based reproducible environment. This means that in setting-up the pipeline, all packages that were used to create the pipeline in the first place are automatically installed to a per-project library. These packages include here v.1.0.1 (Müller 2020) for a streamlined file and directory referencing, terra v.1.7-18 (Hijmans et al. 2022) for spatial processing, data.table v.1.14.8 (Barrett et al. 2023), plyr v.1.8.8 (Wickham 2011), Hmisc v.5.1-1 (Harrell 2023), tidyverse v.2.0.0 (Wickham et al. 2019), and doSNOW v.1.0.20 (Microsoft Corporation and Weston 2022) for general processing, respectively, rtk v.0.2.6.1 (Saary et al. 2017) for rarefaction, vegan v.2.6-4 (Dixon 2003) for calculating diversity indices, usdm v.2.1-6 (Naimi et al. 2014) for variables selection, and jsonlite v.1.8.4 (Ooms 2014) for metadata extraction.\n\nFor set-up, we assume the use of RStudio integrated development environment (IDE) (Racine 2012) and a connection to the internet. First, upon downloading the desired release from GitHub, the user unzips the compressed pipeline file. Second, the user obtains information on the R version required for running the pipeline by inspecting the top lines of the renv.lock file, placed at the root of BEpipeR’s directory structure. If the required version is not available on their system, they obtain it from the Comprehensive R Archive Network and install it. Additionally, on Windows, they ensure that a compatible version of RTools is installed. Third, the user sets the required R version as the default version in RStudio and exits the IDE. Last, BEpipeR’s reproducible environment can be unfolded by opening the BEpipeR.Rproj file using RStudio, upon which the renv package is bootstrapped and all required packages can be installed to the per-project library by typing ‘renv::restore()’ and confirming the prompted dialog with ‘y’. Subsequently, users may want to increase the number of lines retained in RStudio’s console to ensure that all messages generated in running the pipeline are available for post-run inspection. Noteworthy, for visualizing plot locations, the border of Germany must be obtained manually from GADM and stored for its use by the pipeline as ‘Germany_borders.gpkg’ in the pipeline’s ‘Helpers’ directory. For up-to-date set-up instructions, users are referred to the pipeline’s GitHub presence.\n\nParsing information\n\nWith few exceptions (see below), BEpipeR’s flow of operations (Figure 1) is controlled through three csv files (paramMAIN, paramDW, and paramSUB) that are used to parse processing information in a user-friendly fashion. Of these three, paramMAIN is the most instrumental and holds the majority of the aggregation information, whereas paramDW and paramSUB are helper files that coordinate the data wrangling (DW) and subsetting (SUB) steps, respectively. As the Excel versions of these files support users in providing processing information through conditional formatting and functions, we suggest that users provide processing information to these versions first, followed by exporting them to csv file format. While we purposely minimized user interventions to the pipeline’s code, they could not be avoided completely. Currently, user actions might be required at five points (Table 1) marked with the comment string “ACTION POTENTIALLY REQUIRED” in the R script. Users are advised to familiarize themselves with these interventions before executing the pipeline productively.\n\nIncluded are the parameter files used in its operation (left-hand side), its major processing steps (centre), and their sub-steps (right-hand side; italic: optional). Deploying the reproducible environment in setting-up the pipeline is only performed once, and hence greyed out.\n\nThe following parameters cannot be parsed through BEpipeR's parameter files. Instead, they must be provided directly to the pipeline's source code at locations marked with the string “ACTION POTENTIALLY REQUIRED”.\n\nTo demonstrate BEpipeR’s flow of operations and guide users in interpreting the pipeline’s output, we distribute BEpipeR in a ‘just-ran’ state. This means that the pipeline comes with both exemplary input data and the results produced by processing these files (see Use Cases). As indicated (Table 2), exemplary input files must be replaced with real-world Biodiversity Exploratories data when using the pipeline productively to ensure the correctness of results.\n\n‘Provisioning’ describes whether the content is generated automatically or must be provided by the user. Placeholders are surrounded by square brackets. BExIS: Biodiversity Exploratories Information System.\n\nWe support users in providing the processing information required with dictionaries to all three param files that can be found as additional sheets in their respective Excel files. We recommend that users consult this information before starting to work with the pipeline. For exhaustive information on data processing, users are referred to the R script itself, which features comments on the reasoning for each step performed as well as further background information throughout. Additionally, in the following, we provide an in-depth description of the workflow, including details on how to encode the information required, the processing performed, and the output generated, to guide users in familiarizing themselves with the pipeline. Potential abbreviations provided in parentheses after the names of processing steps refer to the prefixes of variable names used in the BEpipeR R script.\n\nData retrieval, exploration, and curation\n\nData retrieval from BExIS database, as well as their exploration and curation are not performed by BEpipeR. Instead, they are performed best by the user on a dataset-to-dataset basis. This approach acknowledges that the decisions on incorporation and processing depend on the user’s aims as well as the unique combination of data and metadata. It further allows users to harness existing workflows for inspecting tabular data. Upon examining both data and metadata, the user decides whether the data set at hand should be processed by BEpipeR, and if yes, provides all the information required for its processing to paramMAIN and, if applicable, paramDW and paramSUB (see below). Subsequently, they copy the respective data set in csv file format (named ‘[baseID]_[version]_data.csv’; square brackets denote placeholders) to BEpipeR’s ‘Source’, as well as its ‘[baseID]_[version]_datastructure.txt’ file to the ‘Metadata’ directory.\n\nSetting-up\n\nFollowing the successful deployment of the reproducible environment through renv and before executing the pipeline, the user decides on one of three possible processing modes: i) forest, for aggregating the Biodiversity Exploratories’ forest data, ii) grassland, for grassland data, or iii) combined, for aggregating both forest and grassland data at the same time. They then provide the corresponding string to the BEpipeR_mode variable in the pipeline’s source code (Table 1). Noteworthy, both ‘Processing’ and ‘Output’ directories are expunged immediately after the start of each pipeline run to avoid potentially outdated files from being mistaken as up-to-date ones. Subsequently, the ‘Processing’ directory is populated by copying all csv data sets from the ‘Source’ directory to this folder. Please note, as data sets are retrieved by their base IDs, BEpipeR does not allow multiple data sets with the same base ID to be present in the ‘Processing’ directory. If this issue is detected, the user is informed and asked to solve the issue.\n\nData pre-processing\n\n1 Template creation: Combining Biodiversity Exploratories data is complicated by two factors. First, most data sets are not spatially explicit per se, meaning they do not feature location information that allows for a straightforward calculation of inter-plot distances. Second, plot information is not provided in a harmonized fashion. This means that the column holding plot designations might be arbitrarily named (e.g., EP, EpPlotID, EP_plot_ID, Useful_EP_PlotID, Plot, PlotID, Plot ID, Plot_ID, or plotid_withzero) and located within the data set. This is further complicated by the presence or absence of leading zeros in plot numbers (e.g., AEW1 vs. AEW01), and two alternative plot encoding schemes (e.g., AEW01 in EP is A18422 in grid plot (GP) encoding). To allow for joining the data regardless of encoding and to maximise its downstream usability, the plot IDs template constructed by BEpipeR holds EP as well as GP designations with and without leading zeros, respectively.\n\nTo allow users to seamlessly use the data generated by BEpipeR in downstream spatially explicit statistical frameworks, the pipeline enriches the template with plot location information harmonized to the World Geodetic System 1984 (WGS84, EPSG: 4326) and informs the user about the spatial imprecision introduced by reprojecting location data from DHDN (Deutsches Hauptdreiecksnetz) to this unified coordinate reference system. Subsequently, the csv version of paramMAIN is imported to the R session as ‘datasets_table’ and filtered for instrumental columns and data sets flagged for inclusion. This table outlines the processing to be performed on each data set and is updated after each major processing step to reflect the progress of the pipeline. Template creation is concluded by various quality checks, including warnings if ‘datasets_table’ features data sets not found in the ‘Processing’ directory, or the system-wide memory available might not be sufficient for executing the pipeline (see Minimal system requirements).\n\n2 Data wrangling (DW): Removing or replacing factually incorrect values is essential in pre-processing data. BEpipeR supports users therein by allowing them to replace or remove these values through exact and pattern-based approaches. To enable this option, the user sets rDW in paramMAIN for the respective data set to ‘yes’. Subsequently, they provide additional information to paramDW, the helper file for this operation. This information includes the data set’s base ID (Dataset_ID), whether the replacement is value- (Class = value) or pattern- (Class = pattern) based, the value to replace (Value_old), and the value to replace with (Value_new). Noteworthy, the pattern-based approach even allows for the deletion of matching rows by specifying Value_new as NULL. In contrast, value-based row deletions are best performed by subsetting (see next step). Generally, modifications are applied in the order of listing (i.e., from top to bottom). This means that multiple modifications can be applied to the same data set by listing the same base ID in multiple rows of paramDW, each time with a different modification.\n\n3 Subsetting (SUB): BEpipeR’s data wrangling capabilities are enriched by its subsetting function, which allows for the filtering of rows using exact matches. To achieve this, upon setting rSUB for the respective data set in paramMAIN to ‘yes’, users provide the following information to this operation’s helper file, paramSUB: the data set’s base ID (Dataset_ID), the name of the column to perform the subsetting on (Subset_variable), the comparison operator to use (Operator), and the entry to retain or remove (Subset_level). As for DW, multiple modifications that are applied consecutively from top to bottom can be requested for the same data set.\n\n4 Fallbacks (FB): Data sets that establish relationships between taxonomic entities and their abundances often feature taxonomic levels not resolved to completion. For instance, a tree species data set might feature aggregated species, such as Quercus spec., alongside species that were fully resolved. To remedy this issue, BEpipeR allows users to perform fallbacks to more basal (taxonomic) levels. To invoke this operation, users set rFB in paramMAIN to ‘yes’ in addition to providing the following information: the name of the column to perform the fallback on (FBcol), the separator used to delineate the different levels of information in FBcol (FBsep), and FBsub, the index of the substring of interest. BEpipeR uses this information to string-split the information in FBcol at the separator specified, upon which the substring of interest is retained by its index. Subsequently, BEpipeR sums abundances per plot at the newly generated factor level, effectively collapsing abundances at a more basal (taxonomic) level. Abundance scores harmonized in this way may seamlessly be used in downstream processing steps.\n\n5 Reshaping (RES): Usually, plot data are most easily processed in wide format, with rows denoting plots and columns representing the respective variables. In this step, BEpipeR allows users to cast data to this format while coding absent combinations as Not Available (NA). To flag a data set for reshaping, the user sets rRES in paramMAIN to ‘yes’, upon which they supply the factors column that will be used in constructing new column names to RESvar. Please note: i) Factors not used in reshaping are collapsed by calculating plot-wise means. Hence, the resulting data set features unique plots in the first column, followed by column-wise environmental data. ii) Due to NA as missing combination value, RES is mutually exclusive with calculating alpha diversity indices (DI, see below). Hence, if you would like to calculate these indices, keep the data in long format. Do not reshape climate data obtained through BExIS’ climate tool to be processed in CLIM (see below) either.\n\n6 Standardization by variable (STD): Abundance scores often rely on sampling effort, with differential effort potentially giving rise to differential abundance, preventing meaningful plot-based comparisons. While various data-dependent normalization/standardization approaches exist (e.g., Weiss et al. 2017, Lin and Peddada 2020, Xia 2023), data sets that feature information on sampling effort are best normalized using this information. To achieve this, BEpipeR allows all numeric variables of a data set to be normalized by information provided in a user-specified column of that data set. To do so, users set rSTD for the respective data set to ‘yes’ and provide the variable’s name to be used for data set-wide standardization (STDvar) to paramMAIN. The result is standardized variables that permit a meaningful and straightforward integration in downstream processing steps.\n\nQuality checks\n\nMulti-mode outlier detection (QC): To support users in their data exploration and to spot potential invalid values, such as un-disclosed numeric NA values or species aggregates that result in artificially high or low abundance scores, BEpipeR performs column-wise outlier detection. This is done upon setting QC in paramMAIN to ‘yes’. To avoid false alarms in non-combined mode (i.e., forest or grassland), plots not conforming to the desired ecosystem are excluded in the detection procedure. In combined mode, outlier detection is performed separately for each ecosystem. Currently, BEpipeR features two outlier detection approaches that are based on constructing confidence intervals as multiples of standard deviation (sd, default: 18) around column means and medians. Noteworthy, lower confidence interval bounds are adjusted according to their column means/medians. More specifically, for a given column, if the lower confidence interval bound is negative but the corresponding column mean/median is positive, the respective lower bound is adjusted to zero. This approach acknowledges that many environmental data might be positive and increases the detection sensitivity of BEpipeR at the lower end of the data distribution. Flagged data sets, filtered for columns with potential outliers, are exported to the global R environment for inspection with the naming scheme ‘QC_[baseID]_flagged_[MEAN|MEDIAN]_[forest|grassland]’. If justified, outliers may be removed by the user through DW, SUB, or a combination thereof. Note that, by default, BEpipeR will not perform QC on climate data obtained through BExIS’ climate tool (base ID: 19007), regardless of what users set QC for this data set to. This is because these data have already been extensively quality-checked; hence, any outliers found are most likely false positives. Future releases of BEpipeR will enhance the outlined detection approaches by utilizing data structure information exclusively obtained through BExIS’ API.\n\nData aggregation\n\n1 Dataset-intern aggregation (DIA): The aim of this step is to construct data-set and plot-level-wise aggregation metrics, regardless of whether data is provided in long or wide format. To accommodate both data structures, BEpipeR provides two aggregation approaches of which one must be provided to the DIAappr column in paramMAIN upon setting DIA for the respective data set to ‘yes’. For either aggregation approach and the grouping variables provided, BEpipeR computes mean, median, sd, and median absolute deviation (mad) values.\n\nDIAappr = 2 allows users to aggregate data in long format. Currently, up to three grouping variables (plot IDs + two non-plot variables) are supported and might be provided to paramMAIN’s DIAcol1, DIAcol2, and DIAcol3 columns.\n\nDIAappr = 3 permits the plot-wise aggregation of data in wide format, meaning only plot IDs as grouping variable are currently supported (i.e., both DIAcol2 and DIAcol3 must be kept empty).\n\n2 Group-intern aggregation (GIA): This step allows users to combine multi-measurement (e.g., multi-year) data split across multiple data sets with the subsequent calculation of summary statistics (mean, median, sd, and mad), while maintaining up to three grouping variables (plot IDs + two non-plot variables). This processing is invoked by setting GIA in paramMAIN to ‘yes’, followed by providing grouping variables to the GIAcol1, GIAcol2, and GIAcol3 columns. Noteworthy, to reduce file sizes, amplicon sequencing data sets might have been shrunk by i) omitting plot × taxonomic unit combinations with zero abundance, and/or ii) deleting all-zero abundance taxonomic units, resulting in deliberately not covering all taxonomic units across all years. The first issue can be corrected for by enabling abundance correction (GIAabcorr = ‘yes’), which effectively rebuilds the plot × taxonomic unit matrix with missing combinations coded as zeros. The second issue is resolved by BEpipeR upon setting taxonomic units correction (GIAtaxcorr) to ‘yes’, which ensures that all taxonomic units are present across all years (absent units are introduced with all-zero abundance). Critical, in paramMAIN’s Group column, users must assign a unique number to the data sets to be combined. In addition, for all focal variables, it is the user’s responsibility to ensure that they are shared between the group’s data sets and that their order of listing in paramMAIN is identical. Future releases of this pipeline will automatize these steps by falling back to the group’s shared variables, followed by their re-organization and processing.\n\n3 Climate (CLIM): BEpipeR’s ability to process environmental data is enriched by its ability to process yearly climate aggregates obtained through BExIS’ climate tool (Wöllauer et al. 2021). To obtain data processable by BEpipeR, users choose the following parameters in the web tool’s graphical user interface for generating their data: Spatial aggregation: separate plots; Aggregation of time: year; options: ‘write all plots in one CSV-File’, ‘one plot timeseries after another’, ‘write header in CSV-Files’, ‘include column “plotID”’, Calendar columns: year. Additionally, they request the parameter description file to be included in the zip archive to be generated. We recommend users to set ‘quality check of measured values’ to ‘3: physical range + step + empirical check’ to obtain climate data that fulfils the highest quality standards. Users are free to choose whether they enable the interpolation of missing values. If they opt to do so, we advise that they request the inclusion of the ‘qualitycounter’ column in their aggregated climate data, which provides information on the total and interpolated number of data points underlying each of the yearly climate aggregates. The presence of this column in the climate data is used as indicator for BEpipeR to remove weakly supported data points (percentage interpolated > 60%), a step that is skipped if this column is not found in the data. If interpolated information is provided by BExIS’ climate tool, users are advised to not re-arrange the data column-wise, as this will break the association between the ‘qualitycounter’ and data columns. However, row-wise operations, such as the exclusion of undesired years through SUB, are permitted.\n\nTo calculate reliable multi-year summary statistics (mean, median, sd, mad, min, and max), BEpipeR allows users to exclude variables not based on a minimal number of data points (i.e., years). By default, this filter is set to four but may be adjusted by users interested in retaining variables that satisfy a more stringent filtering approach (CLIM_min_years, Table 1). These users should keep in mind that, depending on the years they want to obtain temporal coverage over, the replacement of plot HEW02 with HEW51 in 2016 might complicate or even negate the acquisition of long-term time-series climate data. To assist users in this filtering, BEpipeR issues a warning if their strategy is too stringent and results in retaining only few or no climate variables at all.\n\nDiversity calculations\n\nTo go beyond a simple description of abundances, we allow users to calculate alpha diversity indices. To do so, they set DI for the respective data set in paramMAIN to ‘yes’. First, this triggers the reshaping of the respective data set to wide format with zero as value for combinations not present. This step may be skipped for data sets already in this format by providing their base ID to the DI_reshape_whitelist variable (Table 1). Second, users might opt to normalize the data provided through rarefaction by setting RF in paramMAIN to ‘yes’ and providing the number of repetitions to perform (as multiple of ten) to RFnrep. We are well aware of the ongoing debate on proper normalization and the alleged shortcomings of rarefaction (McMurdie and Holmes 2014, Schloss 2024). We acknowledged this by purposely deciding on repeated rarefaction, as an extension of normal rarefaction, for the following reasons: i) rarefaction is a highly tractable and easy-to-grasp concept, ii) data normalized through rarefaction might seamlessly be used in calculating alpha diversity indices (e.g., Walters and Martiny 2020, Schloss 2024), iii) rarefaction might still be the most frequently used normalization technique for amplicon data, and implemented in many processing pipelines such as QIIME (Caporaso et al. 2010) and mothur (Schloss et al. 2009), and iv) rarefaction noticeably decreases the discrepancy between OTU and ASV data (Walters and Martiny 2020, Chiarello et al. 2022), allowing for a higher degree of comparability regardless of the type of clustering applied. Most importantly, repeated rarefaction addresses the often-criticised data loss by random subsampling through performing these subsamplings repeatedly, effectively reducing the impact of single stochastic processes in normalizing data (Cameron et al. 2021). Noteworthy, before repeated rarefaction, potential decimal values in the abundance table that resulted from upstream multi-year aggregations are rounded up to the next integer, an approach that prevents positive values smaller than 0.5 from falsely being set to zero (i.e., absence). Users might gauge the success of the normalization by inspecting rarefaction curves and/or slopes exported to the ‘Output’ directory (Table 3). Following repeated rarefaction and the rounding of potentially produced decimal abundance scores to their nearest integer, BEpipeR computes alpha diversity indices, including species richness, Menhinick (Menhinick 1964), Margalef (Margalef 1973), Shannon-Wiener (Shannon and Weaver 1949), Simpson (Simpson 1949), and the inverse Simpson index. Because most alpha diversity indices are meaningless for empty sampling units, only plots with non-zero richness are retained for later joining.\n\nImportantly, some data sets may be incorporated into BEpipeR’s workflow as they are (i.e., without the need for DIA, GIA, CLIM, RF, or DI). This must be signalled to BEpipeR by setting AsIt in paramMAIN to ‘yes’, upon which no aggregation is performed on these data sets. This functionality allows BEpipeR to incorporate highly sophisticated ready-to-use data sets in a straightforward fashion.\n\nPost-processing\n\n1 Data joining (MRG): Upon ensuring that all data have been processed fully by inspecting the relevant datasets_table columns, BEpipeR left-joins all available data to the plot IDs template constructed upstream. For data sets with leftover grouping variables (apparent by the data set having more rows than the plot IDs template), BEpipeR attempts to accommodate these by repeated reshaping to wide format until the data set’s number of rows conforms to the expectation, or no more potential grouping variables are found. In the latter case, the user is warned. In joining data, BEpipeR appends complete data set IDs to column headers to allow for a straightforward back-tracing of information to their origin.\n\n2 Quality checks (FQC): The aim of this processing step is two-fold. First, BEpipeR performs several quality checks to ensure data consistency and the successful execution of upstream processing steps. For instance, it warns if additional rows were introduced in left-joining, plot designations are found in the values matrix, or if duplicated column headers or headers without data set ID are found, and it maximises the data’s downstream usability by replacing potential spaces in column names with underscores. Second, it removes undesired information from the composite data set constructed in MRG to prepare the data for variables selection (see below) or direct use. This is achieved by replacing NaN (Not a Number) and Inf (infinite) values with NA and excluding non-numeric columns. The resulting intermediate composite data set (FQC_env_var_composite_intermediate.csv, Table 3) might still contain NA cells and mono-value columns. However, it may already be of interest to users who apply statistical frameworks capable of tolerating such input data. This composite data set is processed further by excluding mono-value columns and plots not conforming to the BEpipeR mode specified. Additionally, as some plots might render obtaining a large complete-cases data set difficult by breaking up otherwise continuous long-term time-series data (e.g., HEW51, established in 2016), we allow users to exclude these plots (FQC_plots_to_remove, Table 1) before removing any columns with NA values. The resulting complete-cases composite data set is subsequently exported (FQC_env_var_composite_complete.csv, Table 3). For users applying statistical frameworks capable of processing multi-colinear data, this file may already be used as input for their analyses.\n\n3 Variables selection (VS): Understanding the correlation structure underlying explanatory data is pivotal for the thought- and meaningful interpretation of statistical models. In this processing step, we support users in two ways: i) through BEpipeR, we provide information on correlations underlying the complete composite data set produced in FQC, and ii) condense the data to a set of less correlated variables. Insights into the correlation structure are gained by calculating Pearson correlation coefficients (r) and associated false discovery rate-corrected (Benjamini and Hochberg 1995) P values between all variable pairs in FQC_env_var_composite_complete.csv (Table 3). This information is further used to warn users if significant (P < 0.05) pairwise comparisons with unusually high goodness of fit (r ~ 1) are observed, upon which the user decides whether these comparisons are justifiable or instead indicative of issues in upstream data processing.\n\nReducing the data set to a suite of less correlated variables is achieved by variables selection through variance inflation factor (VIF) analyses. Noteworthy, users might often have justified a priori assumptions about focal variables, and hence would like to retain these in their data set for easier model interpretation. We acknowledge this and provide users with the ability to protect their focal variables from removal by supplying their names to the VS_protected_variables variable in the script (Table 1). To maximise the downstream usability of the data generated, BEpipeR performs variables selection for a range of VIF thresholds from two to ten, with smaller values denoting a more stringent exclusion approach. For each VIF threshold, multiple files are exported to the ‘Output’ directory (Table 3).\n\n4 Metadata compilation and export (COMD): To allow for a straightforward data re-usage, the provisioning of metadata is a cumbersome yet necessary duty to all data scientists. The Biodiversity Exploratories provides these metadata in JSON ‘datastructure’ files for normal data sets and in a csv file for data generated through BExIS’ climate tool. BEpipeR utilizes this information to generate metadata for variables featured in the complete composite data set. To do so, BEpipeR strips away data set IDs and aggregation suffixes from headers. Subsequently, for variable names isolated this way, their metadata (such as variable description and unit information) are extracted, enriched with information on the processing performed through BEpipeR, and exported as tabular data to the ‘Output’ directory (Table 3). Note that, as for data sets, metadata files are retrieved by their base ID, and hence, multiple metadata files with the same base ID are not supported in the ‘Metadata’ directory.\n\nPlaceholders are in square brackets.\n\n\n\n- The data set the variable originates from (with (FullID) and without (BaseID) version suffix).\n\n- Its name as extracted from FQC_env_var_composite_complete.csv (Composite_var).\n\n- Its name after removing processing suffixes (Composite_var_trimmed), as well as the processing information extracted (Aggr_string_1, Aggr_string_2).\n\n- Its metadata as extracted from Biodiversity Exploratories JSON 'datastructure' files (Variables.Id, Variables.Label, Variables.Description, Variables.unit.Name, Variables.unit.Description, and Variables.dataType.Name).\n\n- The processing performed by BEpipeR (in separate columns: rSUB, rDW, rSTD, rRES, rFB, DIA, GIA, RF, and DI; in concatenated fashion: Proc_info). See paramMAIN's dictionary for more information.\n\nMinimal system requirements\n\nTo facilitate the adoption of the pipeline, we designed BEpipeR to be executable even on entry-level consumer hardware. CPU-wise, BEpipeR should execute fine on machines with ≥ 2 physical cores. RAM-wise, its minimal requirements are primarily dictated by the size of the input data sets users opt to process, as well as the type of processing requested. For instance, input files < 100 KB might consume negligible amounts of working memory, while large amplicon sequencing data sets (> 200 MB) might require significantly more, in particular if they are rarefactioned with an excessively high number of repetitions. Still, to prevent working memory from becoming a limiting factor on typical consumer-level hardware, repeated rarefaction is performed in chunks of ten, temporary files might be written to disk (‘Temp’ directory, Table 2), and large elements are cleared from the pipeline’s workspace immediately after they have become obsolete. With respect to processing times, BEpipeR might spend most of its time on the repeated rarefaction of large amplicon data sets, as well as performing variables selection on large composite data sets (> 150 rows, > 1000 columns). However, since these steps harness parallel processing, they can be sped up considerably by switching to more capable hardware.\n\n\nUse cases\n\nTo demonstrate BEpipeR’s rich functionalities with minimal effort to the user, we ship the pipeline with exemplary data, including ten input data sets, corresponding metadata, and filled-out parameter files (Table 2). Both input and metadata files mimic real Biodiversity Exploratories information, which cannot be included for various reasons. In addition, the pipeline includes all files produced by processing the provided input data with default settings (Table 1) to allow users to familiarize themselves with the output produced (Table 3). In the following, we provide a concise summary of the BEpipeR workflow using the provided input data; for brevity, data sets are referred to by their base ID, and only steps required for understanding the provided example are listed. i) Plot designations and location information in data set 20826 are used to construct the spatially explicit plot IDs template. ii) Species abundance data in 19848 contain a non-valid numerical NA value (-88888888), which is replaced with NA in DW. iii) With the entry ‘None’, the abundance data set 19849 contains a non-valid factor level in its plot ID column. This information is excluded through SUB. iv) Species in data set 18269 could not be completely resolved (Genus3_spec), complicating meaningful comparisons between the taxonomic entities in this data set. This is solved by collapsing abundance information at the genus level through FB, followed by reshaping this data to wide format in RES. v) Abundance data in 18526 are not standardized/normalized for sampling effort. Instead, this information is provided in the ‘nobs’ column of this data set, which is subsequently used to normalize abundance scores and restore the inter-plot comparability of the data. vi) After all data sets have passed QC, the two pH measurements per plot provided in 14447 are summarized plot-wise through DIA. vii) Multi-year abundance data split over the data sets 19848, 19849, and 19850 are summarized at plot and species level through GIA. viii) Multi-year climate data (19007) obtained through BExIS’ climate tool is processed by CLIM. Note that, because no ‘qualitycounter’ column is provided, the removal of weakly supported data points is skipped. ix) Amplicon sequencing data in 25067 are first reshaped to wide format, followed by their repeated rarefaction with 150 repetitions, and the calculation of alpha diversity indices. Subsequently, all data are left-joined to the plot IDs template (MRG). Noteworthy, because data set 14567 did not require any processing, it is incorporated as is. The resulting composite data set is quality-controlled and filtered (FQC), and variables selection (VS) is performed. Processing is concluded by the compilation and export of metadata (COMD) to the variables in the complete composite data set constructed in FQC.\n\n\nDiscussion\n\nWith BEpipeR, we provide a feature-rich pipeline for processing and synthesizing Biodiversity Exploratories data. To our knowledge, this is the first framework of this consortium to do so in a user-friendly and highly reproducible fashion. We acknowledge that embedding it in the Biodiversity Exploratories with its many projects comes with both challenges and benefits. We recognise that providing a comprehensive framework for the processing of the consortium’s many data sets is a daunting task, as many, potentially conflicting, interests need to be satisfied. Hence, for the near-time development of this pipeline, we see the following three focal points for improvement: i) Streamlining the user experience by the improved handling of errors, increasing the pipeline’s verbosity, and providing the ability to parse even more aggregation information through the existing parameter files. ii) The extension of existing features, such as data normalization through transformation (e.g., McKnight et al. 2019, Boshuizen and Te Beest 2023). iii) Increasing rigour in ensuring data integrity by implementing access to BExIS’ API and, thereby, information obtainable solely through this channel.\n\nNoteworthy, many re-usability issues BEpipeR corrects for would have been prevented in the first place by adopting more stringent standard operational procedures that ensure data re-usage with minimal user effort. Briefly, we restrict ourselves to the issues encountered most often while working on a subset (~ 150 data sets from 2009 onwards) of the Biodiversity Exploratories’ information stock: i) Non-harmonized plot information: Data re-usage might be drastically improved by encoding plot information in a unified way. This includes, among others, making the plot ID column the first column of data sets, using unified column names for this type of information, and enforcing the experimental plot scheme with leading zeros throughout. ii) Non-harmonized NA and NODATA values: Consortium-wide non-numerical NA and NODATA values would prevent the (mis)use of numerical values for encoding this information. This issue is exacerbated by the fact that information on these values can only reliably be obtained through BExIS’ API, a resource most scientists might not be aware of or familiar with. iii) Non-harmonized encoding of factors: Factors should be encoded as character strings to facilitate their detection and prevent aggregation over these values. These and other potential improvements should be accompanied by more stringent quality control and data curation through the Biodiversity Exploratories’ data management team to prevent mal-formatted, incomplete, or erroneous data sets from being listed as ready-to-use in BExIS database. We also highlight the need to revise any data sets that may not adhere to these standards. While most of these suggestions mean minimal effort for data owners who upload new data sets, and a reasonable yet essential one for this consortium’s data management team, they might drastically reduce hands-on time for scientists that re-use these data, and ultimately pave the way to making these data exploitable through large inter-framework databases (Finkel et al. 2020).\n\nIn constructing BEpipeR, we aimed to balance its specificity to the Biodiversity Exploratories with general applicability. This means that while this pipeline was written to solve numerous Biodiversity Exploratories-specific data issues, it might nevertheless be adapted to the needs of other large research consortia. This might be achieved most easily by, among others, implementing a step that recodes other consortia’s plot designations to the Biodiversity Exploratories’ experimental plot designation scheme, preventing them from having to adjust most regular expression-based pattern matching in BEpipeR. These consortia may also benefit from the modularity of BEpipeR, where each major loop is a well-defined processing step, allowing for straightforward modifications to the workflow. Additionally, parsing-wise, users may tailor paramMAIN to their needs by deleting or replacing all columns not strictly required for BEpipeR’s operation (as indicated in the file’s dictionary). Finally, changes to BEpipeR’s source code are aided by a consistent and traceable naming scheme for variables, as well as detailed comments on the code and the underlying reasoning.\n\nTo conclude, even though this project might be facing substantial challenges, it is the Exploratories’ large base of researchers and scientific staff that has the potential to render this endeavour a success. People interested can contribute both conceptually, by providing suggestions for future implementations, and preferably, by coding. In the best case, their participation is fuelled by having understood the nature of this framework, that is, its capability to boost each project’s data visibility and impact by providing it in a composite data set for the most straightforward re-use possible. As we will demonstrate elsewhere, BEpipeR can be used to generate expansive composite data sets with the potential to further insights into complex evolutionary and ecological matters.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nExample data used in this publication are available as part of BEpipeR on GitHub and Zenodo (Glück et al. 2024).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nAcknowledgements\n\nWe thank the Copyright Office of Tübingen University for their assistance in finding a suitable license for this pipeline and Andreas Ziegler for helping with its shipping. We also acknowledge support from the Open Access Publishing Fund of Tübingen University for covering publication fees. Icons in Figure 1 were obtained from flaticon.com; in their order of first appearance: xnimrodx, lakonicon, Bharat Icons, gravisio, Ida Desi Mariana, phatplus, Freepik, Kharisma, POD Gladiator, Uniconlabs, Iconjam, KP Arts, Mayor Icons, karthiks_18, and IwitoStudio. This work is based on data obtained within the DFG Priority Program 1374 ‘Infrastructure-Biodiversity-Exploratories’. 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}
|
[
{
"id": "341491",
"date": "10 Dec 2024",
"name": "Elliot Gould",
"expertise": [
"Reviewer Expertise Applied ecology / ecological modelling",
"research software development for data analysis pipelines."
],
"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:\nResearch Consortia involved in large-scale long-term environmental research frameworks, such as Biodiversity Exploratories, continuously accrue vast amounts of data. However, a great deal of effort, technical expertise, and data processing infrastructure is required to leverage these data to answer even trivial research questions, let alone more intricate questions.\n\nGlück et al. have developed the BEpipeR tool to facilitate the streamlined synthesis of plot-based Biodiversity Exploratories data. BEpipeR is written in R, one of the most (if not *the most*) popular programming languages in ecology. The approach taken by BEpipeR is a template-based approach whereby the specifications for the data-processing and synthesis pipeline are provided as parameters within .csv files, which are then read in as R objects provided to the main pipeline script.\n\nWhile there might be more sophisticated ways of approaching the task (e.g. the Portal Project) than using parameter inputs or dealing with dynamic analysis contexts via static templates (i.e. data could be in long or wide formats and the user has to specify whether the data is long or wide instead of this being handled automatically); the strength of a simpler approach is that potential errors should be more easily detectible and resolvable by more novice R users, the pipeline can be easily modified, or expanded to other projects.\nAlthough the full computing environment for reproducing and operating the pipeline is not provided, the software environment is provided utilising the renv R package, which is supported by RStudio / Posit, and is a well-known, documented and supported tool. This is a good choice given the target user base of the software are mostly undertaking data synthesis manually with spreadsheets. Although providing the full computing environment through a tool like docker/rocker might enable greater reproducibility and longevity / stability, it would not be approachable to the target user.\nThe software can be downloaded from GitHub, and the user is expected to execute the software using the RStudio IDE, which is also an excellent choice given its popularity, and approachability for new and experienced R users alike.\nSoftware documentation mainly comprises the manuscript under review, as well as the associated README and some markdown files embedded in subdirectories, which gives a neat overview of the purpose and contents of the repository. It's always nice to see a pretty HEX sticker too.\nI have not had sufficient time to properly play with and test the software / code in detail as I would prefer (Ivimey-Cook et al. 2023). But I have briefly explored the main code script and associated files, such as the parameter files, so the majority of my review comprises critiques about the manuscript, and some minimal aspects of implementation.\nThe manuscript was well-calibrated in the level of detail and explanation for the software's target user, and included a good level of detail, in terms of set up / implementation, as well as some nice design choices that facilitate use by less familiar R users. e.g. the choice to include an excel spreadsheet version of the parameter specification files and associated data dictionary sheet, and the distribution of the software in a 'just-ran' state, so that users can get a handle on how the outputs relate to inputs and specification settings. I also particularly liked Figure 1, which gives a great visual overview of the data pipeline.\nMajor Issues & Improvements\nA major issue with the manuscript were the small but frequent grammatical errors and stylistic expression that hampered clarity of meaning. Secondly, the rationale for the software could be more tightly synthesized with relevant literature, which, if addressed, would help in highlighting the utility and merits of the software. Similarly, the discussion could reference related approaches / literature in to contextualise the intended application and contrast alternative approaches to this problem. Minor issues include the need for further clarifying some aspects of the pipeine in appropriate logical sequence, and some further explanation or provision of further resources / user guides for the more complex elements of the software. These are addressed in detail below.\nRationale\n- In reference to your sentence \"By doing so, they might leave out potential data that would have been instrumental in answering their complex scientific questions, ultimately causing a loss in statistical power,\" a loss of statistical power is certainly a big problem caused by not utilising all available data. I think this problem is actually more serious/nuanced than reduced statistical power. For example, another problem is that including or excluding particular subsets of the data may have a large influence on the results and therefore findings (check out some many-analyst style studies for examples of how analytic decisions may have large bearings on the research findings, e.g. Gould et al. in press -- disclaimer, I am first author on this paper, there is no pressure to cite, but we did find that data subsetting could swing numerical results wildly at the boundaries of expected values). - Secondly, this ultimately is also a form of 'research waste.' You could also consider citing Buxton et al. (2021) Ref 2, or Purgar et al. (2022) Ref 3 here. - Considering these additional problems related to a lack of appropriate infrastructure for leveraging available data would further underscore the need for the *BEpipeR* package. - Taking a positive perspective, improving data usage within- and among- consortiums, through utilising tools similar to *BEpipeR* would contribute to the task of data / evidence synthesis, and potentially tackling broader empirical research questions, around generality, for example. - Tools, such as *BEpipeR*, support good data stewardship and data management with a long-term vision which ultimately support scientific discovery and progress (Wilkinson et al. 2016) Ref 4\nOther Related Literature / Applications\n- Portal Project and associated package (addresses the same problem as BEpipeR, but for the Portal Project): https://portal.weecology.org https://github.com/weecology/portalr (Christensen et al. 2019) Ref 1 - \"Regularly updated data\" (Yenni et al. 2019) Ref 5-- a potential use-case for BEpipeR as new monitoring data is collected over time. - \"Near Term forecasting\" (White et al. 2019) Ref 6-- another potential use-case for BEpipeR that could be incorporated into automated pipelines when the software matures into the future.\nUse-case demonstration\n- I found the textual summary of the use-case was rather onerous to read. This could be better presented as a diagram / schematic, perhaps with snapshots of the data, and a summary of the user-settings at various phases of the pipeline.\nMinor Issues\n- abstract:\n\n- Background: I think a clause qualifying what Biodiversity Exploratories is (\"Large-scale long-term environmental research frameworks\") in the abstract would be handy, perhaps at the end of the final sentence in the 'Background' component of the abstract. - Implementation:\n\n- It was nice to see an explanation of the setup that includes an explanation of `renv`, I suggest providing a link to the user-guide (https://docs.posit.co/ide/user/ide/guide/environments/r/renv.html), given the target audience are not experienced R users. I've personally experienced a bit of difficulty with `renv` at times, even thought I consider myself to be at the pointy end of things.\n\n- \"For up-to-date set-up instructions, users are referred to the pipeline’s GitHub presence\" - I suggest qualifying the exact location. When I went to find where this information might be, I could only find the same content stored as a markdown file.\n\n- \"As the Excel versions of these files support users in providing processing information [...]\" - the fact that there are .xlsx versions of the same .csv files hasn't yet been introduced in this paragraph. I suggest stating so clearly and rewording. I had to go to the repository to be sure of the intended meaning here. - Table 2:\n\n- Move \"Source\" row above \"Processing\" since the content of \"Processing\" is the product of \"Source\": \"Files copied here from ‘Source’ for processing through BEpipeR. This directory is expunged at the start of each pipeline run.\"\n\n- \"The R programming language script of the BEpipeR pipeline\": replace \"of the\" with, \"that executes\", or similar. - Data preprocessing:\n\n- \"R session as ‘datasets_table’\" should be \"global environment for the active R session as the object ‘datasets_table’\".\n\n- In my experience reshaping data between long and wide formats can sometimes be non-trivial. I would suggest giving users a warning here to check the outputs are as expected after reshaping. An example of the data reshaping inputs and outputs might also help exemplify this process a little further. Perhaps as a vignette in the repository or in a text-box. I found the reshaping a little hard to mentally visualize from the text description.\n\n- The 'standardization by variable' paragraph was also a little tricky to follow. It's stated that \"BEpipeR allows all numeric variables of a data set to be normalized by information provided in a user-specified column of that data set\", what is the specific normalization procedure used? This should be mentioned so that the user can understand the calculation fully. I assume from the previous sentence in the paragraph mentioning sampling effort, and from reading below that the standardization approach is rarefaction? - Quality Checks\n\n- It seems that outlier checks might be performed once (maybe twice?) by the user, and that after running the pipeline once to flag potential outliers, the user can then remove outliers, and then re-run the pipeline to completion. After doing so, should the user then turn off the quality checking? Figure 1 gives the impression of a somewhat linear pipeline, but perhaps the process is more iterative depending on actions taken after QC. A little more explanation of the overall workflow here would be handy. - Diversity calculations\n\n- Which exact procedure is used to \"calculate alpha diversity indices\"? This isn't mentioned until the very end of the paragraph, which follows very detailed treatment of the contentious nature of rarefaction. - Post-processing\n\n- \"BEpipeR left-joins all available data to the plot IDs template constructed upstream.\" The target user is not going to know what a left-join is, most likely. Perhaps you could provide a link to R4ds, which explains this procedure further: https://r4ds.hadley.nz/joins . https://r4ds.had.co.nz/relational-data.html#outer-join has a really nice diagram depicting and explaining this. - Conclusion\n\n- \"People interested can contribute both conceptually, by providing suggestions for future implementations, and preferably, by coding.\" This needs a little further explanation, i.e. people can contribute by making pull-requests to the package's code-base on GitHub.\nReferencing\nI don't think Baker (2016) is the right reference for the statement \"Arguably, BEpipeR has the potential to generate large composite data sets in a highly reproducible fashion.\" Either you meant to cite Baker (2017), which is also in your reference list, or you should cite something more focussed on the intersection of data pipelines / infrastructure and reproducibility.\nSoftware Citation Style\nInstead of having a very long sentence chewing up a whole paragraph containing all of the software used in your package, consider using a table of package citations, e.g. following the citation report approach taken by the *grateful* package, summarising packages within a table.\nExpression\n- At times the writing was hyperbolic and not so succinct, e.g. \"fuelled by\" (perhaps replace with, \"underpinned by\") and \"unmatched standing expertise\", \"To conclude, even though this project might be facing substantial challenges, it is the Exploratories’ large base of researchers and scientific staff that has the potential to render this endeavour a success.\" I think an additional edit for succinctness and clarity of expression is needed. - Overuse of demonstrative particles, such as 'this', 'that', 'these' combined with nominalization at times hampered clarity and slowed my understanding, e.g. of nominalisation: \"that allow for a straightforward and less time-consuming incorporation into their workflows\". Suggest switching to more active language. This will also help with succinctness. - \"executing the pipeline productively\" it's not clear what 'productively' means here. Do you mean 'in production'? - \"Additionally, in the following, we provide an\", replace with \"Below we provide an\" - Shift \"to guide users in familiarizing themselves with the pipeline\" after \"an in-depth description of the workflow\".\n\nGrammatical, spelling, typographical errors\n- \"data subsettings\": 'subsetting' is plural. - \"data substitution through exact and pattern-based approaches\", do you mean 'subsetting'? - \"resolving species aggregates issues\", replace \"species aggregates\" with 'species aggregation' or similar. - First sentence of last paragraph in introduction is extremely long, and the clause following the semi-colon seems incomplete grammatically.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Partly\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": []
},
{
"id": "351632",
"date": "23 Jan 2025",
"name": "Matthias Grenié",
"expertise": [
"Reviewer Expertise biodiversity metrics",
"biodiversity tools"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI was asked to review the BEPipeR manuscript, as a great tool for the Biodiversity Exploratories. While clearly a huge amount of work was put into designing and creating the pipeline, I do have strong reserves regarding its ease of use and clarity as a tool.\nOne first question I had while reading the manuscript was to know what BEPipeR were. From reading the manuscript, this wasn't clear from the beginning. I would have expected BEPipeR to be an R package or a shiny application, as it aimed to simplify data access and analysis for the user. I understood, after finishing the introduction that it was indeed an R pipeline, but I was wondering what the added benefit was compared to an R package or a shiny app? It seems to me that a pipeline is more brittle to change than a well defined R package. It's also harder to distribute as it doesn't uses the main mechanism to spread analyses through R which are R packages. It also doesn't leverage the \"Research Compendium\" suggested by Marwick et al. (2018) and others at the same time (see https://github.com/benmarwick/rrtools). That infrastructure tries to provide the best of both world between R packages and pipelines. Research compendia can be spread through https://docs.r-universe.dev/ for easy install and leveraging the default installation mechanism of R. I think the author should also be clear why choosing not to create an R package was better to help user and instead creating a full pipeline with many specificities.\nOne main question I think the authors should take some time to answer is to identify their target audience. Who are they addressing to? Are the users going to be people comfortable editing an R script? Would they rather edit a clear configuration file? How about people who want to tweak their own pipeline? I think this work should be preliminary to building such a complex tool, as BEPipeR is targeting several user types without clearly facilitating their work: you both have to edit the R script for specific values and get your own configuration files. One good way of identifying the target audience, is to run tests runs of the software with potential users to gather feedback about what was clear and what wasn't. This is invaluable when building a tool, to make sure what you're creating is (1) going to serve the users' needs; (2) be used; (3) easy to use.\nWhether it was within the manuscript or the GitHub repository, I found difficult to get a quick overview of what was achievable with BEPipeR. Before following the entire script it isn't clear what the main functions of BEPipeR are. What are the core functions of BEPipeR? You could show quick snippets of plots generated through the BEPipeR pipeline or data analyzed with it on the GitHub page or within the manuscript. The fact that I had to manually go through the script to understand what was achieved concretly by BEPipeR prevents me from using it as I didn't know how it could help before hand. In addition to \"Setting up\" instructions, you could provide a \"Where to start\" section to clear define the goals and possibilities offered by BEPipeR. Also, these instructions should be available within the GitHub repository, as not all users are going to refer to the manuscript to understand the basic features of BEPipeR. One thing that would be nice would be to see where BEPipeR stands in terms of the analysis pipeline of the Biodiversity Exploratories datasets.\nRegarding installation of BEPipeR, I had a hard time setting up with the exact version of R and thus installing the Pipeline, I had to install [rig]() to be able to switch R versions as R 4.1.1 is already considered quite old. I had to use admin privileges to install `rig`, then use a command line instruction to install the specific R version, than load RStudio with the good version of R, then restore the `renv` file. I'm unsure if the average user of the pipeline would be confident to perform such a long and complicated process. Also, it doesn't seem to be a good idea to have several R versions laying around your computer. This can definitely confuse your users. While I understand the need to fix package version to ensure maximum reproducibility, I urge the authors to point the users to a \"simple\" way of doing so. After about an hour of struggle, I managed to install all versions of needed software (previous R version, previous version of RTools, and the `renv` environment). I really wonder to what extent this process is easily extendable to other users, and this, to me, emphasizes the fact that building an R package with clearly defined package versions would make the full process easier. Also, if BEPipeR requires all that, while needing an R connection, I don't understand why it requires to manually download the GADM German gpkg file instead of providing a function to download it at the good place. Also, it puts the burden on the users' shoulders where they have not only to download but also rename it properly and move it in the appropriate folder. A user can stumble over any of each of these steps.\nRegarding the pipeline, as advertised in the manuscript as \"user-friendly processing of data sets\", I was expecting a clear separation between the features provided by BEPipeR and the script that needs to be tweaked by the users. What I found was quite hard to understand: a 3000-lines R script, with both user-input values mixed up with actual functional code to process the dataset. I found this structure impossibly complex for the feature. I would have expected some functionality to be \"packaged\" somehow, if not in an R package, at least in some R/ folders with local functions. Understanding what parts of this script were to be modified and which ones shouldn't was quite difficult. Even though everything was explained in much details in the manuscript, I had trouble connecting the manuscript to the actual script. I would have expected the manuscript to more explicitly show parts of the script to explain how it works. Instead the manuscript goes in great length explaining what the script does, without explaining how to use it! For example, the param*.csv files are loaded in the script at three different locations, why is that? Do you expect the user to go through these three locations to understand what's happening? The three files could be loaded at the top of the script to easily separate between user input and data loaded automatically. Also, even though there are dictionaries provided for the design of each of these files, the structure for variable selection is quite hard to understand what these files are and how to create them. I think extensive documentation of these files, with verbal description and schemes showing how they connect to the pipeline would help. The three param files are mentioned in Figure 1, but it's really unclear how they connect to the pipeline exactly. What do they provide and how are they reused throughout the analysis?\nRegarding script structure, one thing possible would be to divide the script into smaller scripts to abstract away some details and better structure the code. With each script calling common functions, or at least calling one another. The main script doesn't follow RStudio's syntax to create clear parts that the user can jump through using the \"Show Document Outline\" feature, the convention is that any comment in R followed by text and four times the same character is considered \"a part\" of the script. This makes navigating the script harder, especially if you're expecting the user to use RStudio.\nAnother thing that puzzled me, whether in the manuscript or the software documentation is that nowhere was explained how I should run the script. Should I run `source()` directly on the main script? With which working directory? Which parameters should I make sure to have changed? Should I run the script line-by-line or section by section? This should be clearly stated as a naive user would want to know this information rapidly when downloading the pipeline.\nWhile the paper is a great companion to explain how to use BEPipeR, I think the pipeline should be self-sufficient and contain enough documentation to be able to operate the pipeline without referring to external documentation. The documentation should be extensive about the steps, both about what analyses are performed but also, and it's quite important for a pipeline, how to perform them, with which possible options.\nHave you tested it against users? What was their feedback? I would be curious to know as I expect the use of such a script to be quite complex for naive users. I would definitely recommend the authors to simplify the features they want to work on, to compartimentalize their pipeline through well-defined functions made available to the users, and simplify the final script exposed to the user, with easy to run routine. Like \"run this main script that is going to call internal functions\". The authors could also look into building a [targets](https://docs.ropensci.org/targets/) pipeline for ease of reproducibility.\nI had two additional small remarks: the first one is I congratulate the authors for having thought about archiving their software on Zenodo in addition to GitHub as it allows near-permanent archival. The second is that I enjoyed seeing the hexagonal logo of BEPipeR but it doesn't seem specific enough to be related to Biodiversity Exploratories. Maybe you could think about a logo that reuses parts of the graphical identity of Biodiversity Explaratories.\n# References 1.) Marwick et.al., 2018 (Ref 1)\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1268
|
https://f1000research.com/articles/13-754/v1
|
05 Jul 24
|
{
"type": "Systematic Review",
"title": "Natural agents that are neuroprotective against mitochondria: a bibliometric-based research mapping 1998–2024, from cells to mitochondria",
"authors": [
"ARMAN YURISALDI SALEH",
"Dwi Arwandi Yogi Saputra",
"Dwi Arwandi Yogi Saputra"
],
"abstract": "Introduction Mitochondria are cell organelles that function as the cell’s main power plant, producing ATP, the main energy molecule in cells. Mitochondria play an important role in the context of neuroprotection, and mitochondrial function has been implicated in various neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS). Recent research in the field of neuroprotection has focused on the development of therapies that target mitochondria. Natural ingredients have long been used in traditional medicine and show potential as neuroprotective agents.\n\nMethods In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords natural agents, herb*, neuroprotective, and mitochondria. The data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analyses.\n\nResults The research trend found are documents by year, most global cited document, most relevant sources, A factorial map illustrating the leading contributors of papers, documents by author, documents by country or territory, documents by subject area, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map, thematic evolution, cluster analysis, qualitative analysis, and word cloud.\n\nConclusions Natural Agent Neurotropik is a natural substance that influences the brain’s nervous system and peripheral nervous system, enhancing cognition, mood, and brain function. Derived from herbs, spices, and herbal products, it has advantages over other natural agents in energy production, brain biogenesis, and neuroprotection.",
"keywords": [
"herbs",
"herbal",
"natural",
"agent",
"neuroprotective",
"mitochondria"
],
"content": "Introduction\n\nMitochondria are cell organelles that function as the cell’s main power plants, producing ATP, the main energy molecule in cells. Mitochondria also play a role in various other processes such as the citric acid cycle, fatty acid oxidation, and amino acid metabolism. Therefore, mitochondria are essential for the normal functioning of cells and the organism as a whole.\n\nIn the context of neuroprotection, mitochondria play a very important role. Impaired mitochondrial function has been linked to a variety of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS).1 Therefore, recent research in the field of neuroprotection has focused on the development of therapies targeting mitochondria.1\n\nNatural ingredients have long been used in traditional medicine and have shown potential as neuroprotective agents.1 Several natural substances have been shown to have neuroprotective effects, either through improving mitochondrial function or through other mechanisms1. Several natural substances have been shown to have neuroprotective effects, either through improving mitochondrial function or through other mechanisms.1\n\nAnother advantage of natural substances is that they are often cheaper and more accessible compared to synthetic drugs. Additionally, natural ingredients often have fewer side effects, making them a better choice for many patients. However, more research is needed to fully understand how these natural ingredients work and how they can be used in the most effective way.1\n\nOverall, research on the importance of mitochondria in neuroprotection and the potential of natural products as neuroprotective agents is a very promising area. With more research, we can develop new, more effective, and more efficient therapies for neurodegenerative diseases.\n\n\nMethods\n\nBibliometric research is a research method that uses scientific publication data to describe and analyze the development of a field of science. This research aims to identify and map trends, patterns, and relationships between scientific documents related to certain topics. In this research, the topic chosen was natural agents, herb*, neuroprotective and mitochondria. This research uses data from the website www.scopus.com, which is one of the largest and most trusted databases for scientific publications. This research was conducted on early March 2024.\n\nTo carry out bibliometric research, the steps to follow are as follows:\n\n1. Determine search keywords. In this research, the keywords used are natural agents, herb*, neuroprotective and mitochondria. These keywords are entered into the search column on the www.scopus.com site by selecting the topic field (title, abstract, keywords).\n\n2. Filter search results. In this study, Were not filtered.\n\n3. Retrieve the data from the search results and save it to your device. This study involves the downloading of search result data in three distinct formats, which are:\n\n• CSV (comma-separated value), The document includes fundamental details such as the title, author, affiliation, year, source, abstract, and keywords.\n\n• RIS (research information system), The text contains comprehensive information, including the sources cited within it.\n\nData for this study were collected by one reviewer. Reviewers work independently in collecting data from each report. To ensure data accuracy and clutter. In addition, we use automated tools, namely the *VosViewer* and *Biblioshiny* applications, to assist in the data collection and analysis process.\n\nIn this study we found are documents by year has been an increase in the number of documents; until 2020, there were 23 documents, most global cited document that received the most citations with 391 citations, most relevant sources is journal ethnopharmacology, A factorial map illustrating the leading contributors of papers, documents by author with the most authors with 8 documents are Oh, M.S., documents by country or territory with China has the highest number of documents among all countries, 144 documents, documents by subject area, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map based on the title shows that the niche theme is the keyword mitochondria signaling pathway, effects neuroprotective effect, dan oxidative stres toxicity, thematic evolution, cluster analysis, qualitative analysis, and word cloud.\n\nWe used the following terms to do a search on the Scopus website, taking into consideration that this website contains research that is considered to be valid: TITLE – ABS – KEY (natural agents) OR TITLE – ABS – KEY (herb*) AND TITLE – ABS – KEY (neuroprotective) AND TITLE – ABS – KEY (mitochondria) are the titles of the products that are under consideration. Two hundred and forty three documents were received by us. We then save the document from Scopus in the form of a file with the extension.csv following this step.\n\nBoth the Biblioshiny and Vosviewer software packages were utilised in the analysis process.\n\nDocuments by year\n\nBased on Figure 1, it appears that there has been an increase in the number of documents; until 2020, there were 23 documents. The oldest document in 1998 was entitled Protective Effects of Schisanhenol Against Oxygen Free Radical-Induced Injury of Rat Cerebral Mitochondria and Synaptosomes, written by Li, L. Liu, and G.2 Meanwhile, the latest document in 2024 is entitled Exploring the effect of Anshen Dingzhi prescription on hippocampal mitochondrial signals in a single prolonged stress mouse model, written by Juan Wang et al.3\n\nMost global cited document\n\nBased on Figure 2, The document that received the most citations, with 391 citations, was the one written by Anjum A et al. in 2020 with the title Spinal cord injury: pathophysiology, multimolecular interactions, and underlying recovery mechanisms.4 Published in the International Journal of Molecular Sciences. In the next position, with 317 citations, is the journal written by Wang R., Yan H., and Tang X.-C. in 2006 in the Journal Acta Pharmacologica Sinica entitled Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine.5 In third place with 201 citations are written documents by Wang T et al. in 2009 in the Journal Free Radical Biology and Medicine entitled Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-κB pathways and inhibition of intracellular ROS/RNS generation.6\n\nMost relevant sources\n\nBased on Figure 3, The following are the journals that publish the most important documents: Journal Ethnopharmacology, founded in 1979 by Dr. Norman R. Farnsworth, is a leading journal in the field of etnopharmacology, focusing on traditional drug use by society worldwide. It has been indexed by Scopus since 1985, indicating its high quality and reputation in the scientific community. Published by Elsevier B.V., the journal has a strong presence in the etnopharmacology field, with a strong SCImago Journal Rank of 2.354 in 2022. The journal publishes various types of articles, including asli, literature review, single communication, and methodology, and covers various topics in ethnopharmacology, such as ethnopharmacology, drug biology activity, active identification, and traditional drug use.\n\nJournal Neurochemical Research is a scientific journal focused on neurochemistry, publishing articles on various aspects of neurochemistry, including molecular mechanisms, neurochemistry regulation, system development, and neurology. It aims to enhance our understanding of the function and properties of the nervous system through high-quality research. The journal has a Quartile Scopus level, making it a significant contribution to neurochemistry. It is published by [insert publisher name], has a solid reputation, and has a high SCImago Journal Rank (SJR value for 2022), indicating its significant contributions to neurochemistry. It also offers various types of articles, reviews, reviews, and reviews to promote research and development in neurochemistry.\n\nFactorial map of the documents with the highest contributes\n\nIn Figure 4, the following is a factorial map of the documents with the highest contributions based on title. The most contributing document was that written by Wu L-K in the journal Phytomedicine Pada Tahun 2022 with the title Artemisia Leaf Extract Protects Against Neuron Toxicity by TRPML1 activation and Promoting Autophagy and Mitophagy Clearance in Both in vitro and in vivo Models of MPP+/MPTP-induced Parkinson’s Disease.7\n\nDocuments by author\n\nBased on Figure 5, the most authors with 8 documents are Oh, M.S. with the title of the article: Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson’s disease.8 Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo.9 Sanguisorbae radix protects against 6- hydroxydopamine-induced neurotoxicity by regulating NADPH oxidase and NF-E2-related factor-2/heme oxygenase-1 expressions.10 Houttuyniae Herba protects rat primary cortical cells from Aβ -induced neurotoxicity via regulation of calcium influx and mitochondria-mediated apoptosis.11 Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2, 3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions.12 Dangguijakyak-san, a medicinal herbal formula, protects dopaminergic neurons from 6-hydroxydopamine-induced neurotoxicity.13 Protective effects of chunghyuldan against ROS-mediated neuronal cell death in models of parkinson’s disease.14 Evaluation of Samjunghwan, a traditional medicine, for neuroprotection against damage by amyloid-beta in rat cortical neurons.15\n\nThe next most author with 6 documents is Kim, H.G. with the title of the article: Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo.9 Sanguisorbae radix protects against 6-hydroxydopamine-induced neurotoxicity by regulating NADPH oxidase and NF-E2-related factor-2/heme oxygenase-1 expressions.10 Dangguijakyak-san protects dopamine neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity under postmenopausal conditions.12 Dangguijakyak-san, a medicinal herbal formula, protects dopaminergic neurons from 6-hydroxydopamine-induced neurotoxicity.13 Protective effects of chunghyuldan against ROS-mediated neuronal cell death in models of parkinson’s disease.14 Evaluation of Samjunghwan, a traditional medicine, for neuroprotection against damage by amyloid-beta in rat cortical neurons.15\n\nThe next most author with 4 documents is Lo, Y.C. with the title of the article: The Chinese herbal formula Liuwei dihuang protects dopaminergic neurons against Parkinson’s toxin through enhancing antioxidative defense and preventing apoptotic death.16 Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells.17 San-Huang-Xie-Xin-Tang protects against activated microglia- and 6-OHDA-induced toxicity in neuronal SH-SY5Y cells.18 Neuronal effects of 4-t-Butylcatechol: A model for catechol-containing antioxidants.19\n\nDocuments by country or territory\n\nBased on Figure 6, China has the highest number of documents among all countries, 144 documents. Followed by South Korea with 30 documents, the United States with 13 documents, Taiwan with 12 documents, and India with 10 documents.\n\nDocuments by subject area\n\nNetwork visualization\n\nBased on Figure 8, it can be seen that the areas studied are still not related to other areas that are divided into edges. That field is: peptide fragment, peptide fragments, pc12 cell line, glucoside, proteins c-akt, antagonist and inhibitors, protein kinase, molecular docking, sequestosome 1, nissl staining, histology, mitochondrial respiration, brain infraction, histology, oxygen, isoflavones, bcl-2 associated x protein, membrane potential, blotting western, cell strain, flavonoid, brain edema, curcumin, pathogenesis, blood brain barrier, cell strain, blotting westen, inflammation, anti-inflammatory activity, neuroinflammation, neurotoxins, neurotoxin, Animalia, drug targeting, mptp poisoning, saponins, cyclooxygenase 2 and substantia nigra.\n\nOverlay visualization of scopus, database using vosviewer\n\nBased on Figure 9. In the overlay visualization, it appears that the keywords that are being researched a lot approaching 2020 are the parts colored yellow, namely: sequestosomoe 1, mitophagy, nissl staining, curcumin, astrocyte, anti-inflammatory activity, neuroinflammation, and Chinese herbal.\n\nDensity visualization\n\nBased on Figure 10. In the visual circulation density, it appears that the part that is already saturated with research is yellow, while the part that is not yet saturated is slightly yellow and dominantly green, namely keywords. : peptide fragment, peptide fragments, protein kinase, molecular docking, sequestosome 1, amyloid beta-peptides, ayloid beta protein, pc12cell line, glucoside, proto-oncogene proteins c-akt, cell damage, Chinese herb, glucose, mitophagy, nissl staining, apoptosis inducing factor, donepezil, brain cortex, oxygen, brain injury, histology, reperfusion injury, mitochondrial respiration, ischemia, protein kinase b, antagonist and inhibitors, isoflavones, bcl-2 associated x protein, blotting western, cell strain, rna messenger, herbicidesm neurotoxins, neurotoxin, mus, mptp poisoning, free radical scavengers, nerve degeneration, substantia nigra, levodopa, saponins, cyclooxygenase 2, drug targeting, animalia, plant root, ginsenosides, free radical, nerve growth factor, astrocyte, panax, anti-inflammatory activity, neuroinflammation, ginseng, dna damage, pathogenesis, vasculotropin, curcumin, multiple sclerosis, flavionoid, brain edema, gallic acid, brain infarction, and motor dysfunction.\n\nThematic map\n\nBased on Figure 11, Thematic map based on the title shows that the niche theme is the keyword mitochondria signaling pathway, effects neuroprotective effect, dan oxidative stres toxicity.\n\nThematic evolution\n\nBased on Figure 12. In Thematic evolution based on the title There appears to be a change in theme in research from 1998 to 2017. The keyword cell changes to mitochondria in the research theme in 2024.\n\nCluster analysis\n\nFrom Table 2 above, there are 6 clusters based on keywords.\n\nCluster 1, dominated by Nonhuman, Neuroprotection, and Unclassified drug\n\nCluster 2, dominated by Article, Controlled study, and Neuroprotective agents.\n\nCluster 3, dominated by Animals, Mitochondria, and Neuroprotective agent\n\nCluster 4, dominated by Enzyme activity, Mice, and Neurotoxicity\n\nCluster 5, dominated by Mitochondrion, Nerve cell and in vitro study\n\nCluster 6, dominated by Rattus, Cytology; and Mice, inbred icr\n\nTable 3. Natural agents herbs that function as neuroprotective mitochondria in Scopus-indexed journals:\n\nWord cloud\n\nBased on Figure 13. Word Cloud shows that the dominant word in the document is the word mitochondria, followed by oxidative stress, neuroprotection, Parkinson’s disease and apoptosis.\n\n\nDiscussion\n\nNatural neurotropic agents refer to natural compounds that have the ability to affect the central nervous system and peripheral nervous system. This compound has been widely researched in the context of medicine and brain fitness. Introduction to Natural Neurotropic Agents provides a basic understanding of these compounds and introduces their various effects on the function of mitochondria, which are vital organelles in cells.\n\nNatural neurotropic agents can be defined as natural compounds that have neurotropic properties, namely the ability to influence the nervous system. The main characteristics of natural neurotropic agents include neuroprotective effects, improving cognition, improving mood, and improving nerve function at the cellular level. These compounds can come from natural sources such as plants, herbs, and other natural ingredients.\n\nThe role of natural neurotrophic agents on mitochondria is very important because mitochondria are the main energy source of cells and have a key role in nerve function. Natural neurotropic agents can influence mitochondrial function by increasing energy production, increasing mitochondrial biogenesis, and protecting mitochondria from oxidative damage. Thus, these compounds can help maintain nerve health and prevent various neurodegenerative disorders.\n\nNatural neurotropic agents have several advantages compared to chemical drugs in the treatment and care of nerves. First, these natural compounds tend to have fewer side effects and are safer to use in the long term. Second, natural neurotropic agents often target multiple biological pathways in the nervous system, providing a more holistic and comprehensive effect. Third, these natural compounds are generally easier to find and widely available on the market. Therefore, natural neurotropic agents offer an attractive and relevant alternative in the treatment and care of neurological conditions.\n\nThere are several natural neurotropic agents that are widely discussed in the Scopus reindex document. One of them is Panax notoginseng with ginsenoside. Research shows that the ginsenoside substance contained in Panax notoginseng has significant neurotrophic effects.93,106,128,135 Apart from that, Huperzine A is also a natural neurotropic agent, which is in great demand. Huperzine A has been shown to have neuroprotective properties and may improve cognition.5,98,162,230 Berberine, found in some plants such as cinnamon, is also of interest in neurotrophic studies. Berberine may protect mitochondria and reduce oxidative stress in the nervous system.17,21,64,67,225,231 Curcumin, the active compound in turmeric, also has significant neurotrophic effects. Studies show that curcumin can protect nerve cells from oxidative damage and inflammation.30,67,79,136,194 Salvia miltiorrhiza and Artemisia have also been shown to have interesting and potential neurotrophic effects. Further research is needed to understand the mechanism of action and potential uses of this natural neurotropic agent.101,108,173,204,208,220,233,234\n\nPanax notoginseng with ginsenoside, humperzine A, berberine, curcumin, Salvia miltiorrhiza, and Artemisia is a natural neurotrophic agent available on the market. Bibliometric research reveals that the availability of each of these natural ingredients has received great attention. Panax notoginseng with ginsenoside was found to have strong neurotropic properties and is able to affect mitochondria. Huperzine A is recognized for its ability to improve cognitive function and protect nerve cells. Berberine is known to have neuroprotective and antioxidant effects. Curcumin has significant anti-inflammatory and neuroprotective properties. Salvia miltiorrhiza has neurotrophic effects and protects mitochondria from oxidative stress, whereas Artemisia has promising neuroprotective potential. The availability of all these natural neurotropic agents on the market allows people to consume them and get the benefits proven by research.\n\nPanax notoginseng with ginsenoside is one of the natural neurotropic agents available on the market. Bibliometric research shows that the availability of Panax notoginseng with a ginsenoside substance has received great attention. This natural ingredient has strong neurotropic properties and is able to affect mitochondria. Ginsenoside, the active compound contained in Panax notoginseng, has been shown to have neuroprotective effects and improve cellular signaling in mitochondria. The availability of Panax Notoginseng with Ginsenoside on the market allows people to use it as a natural medicine for brain and nervous system health93,106,128,135\n\nHuperzine A is a natural neurotropic agent available on the market. Bibliometric research shows that the availability of Huperzine A has received great attention. This natural ingredient is recognized for its ability to improve cognitive function and protect nerve cells. Huperzine A works by inhibiting the enzyme acetylcholinesterase, thereby increasing acetylcholine levels and improving nerve signal transmission. With the availability of Huperzine A on the market, people can consume it as a supplement to improve memory and brain function naturally5,98,162,230\n\nBerberine is one of the natural neurotropic agents available on the market. Bibliometric research shows that the availability of berberine has received great attention. This natural ingredient is known for its neuroprotective and antioxidant effects. Berberine works by inhibiting the activity of enzymes involved in inflammatory processes and oxidative stress in nerve cells. With the availability of berberine on the market, people can consume it as a natural medicine that is effective in protecting the brain and nervous system from damage17,21,64,67,225,231\n\nCurcumin is one of the natural neurotropic agents available on the market. Bibliometric research shows that the availability of curcumin has received great attention. This natural ingredient has significant anti-inflammatory and neuroprotective properties. Curcumin works by inhibiting the activity of inflammatory molecules and reducing nerve cell damage due to oxidative stress. The availability of curcumin on the market allows people to use this natural ingredient as a supplement to maintain brain health and reduce the risk of neurodegenerative diseases30,67,79,136,194\n\nSalvia miltiorrhiza is one of the natural neurotropic agents available on the market. Bibliometric research shows that the availability of Salvia miltiorrhiza has received great attention. This natural ingredient has neurotrophic effects and protects mitochondria from oxidative stress. Salvia miltiorrhiza extract has been shown to increase nerve cell growth, reduce inflammation, and protect mitochondria from damage. With the availability of Salvia miltiorrhiza on the market, people can use it as an effective natural medicine to improve brain health and reduce the risk of neurodegenerative diseases101,108,173,204,208,220,233,234\n\nArtemisia is one of the natural neurotropic agents available on the market. Bibliometric research shows that the availability of Artemisia has received great attention. This natural ingredient has promising neuroprotective potential. Artemisia contains active compounds that can protect nerve cells from oxidative damage and increase nerve cell growth. The availability of Artemisia on the market allows people to consume it as a natural medicine or supplement to maintain the health of the brain and nervous system7,110\n\nThis bibliometric research has highlighted a number of neurotrophic natural agents that have potential benefits in consumption. This study categorizes natural neurotrophic agents that are widely discussed in Scopus index documents, such as Panax Notoginseng with Ginsenoside, Huperzine A, Berberine, Curcumin, Salvia miltiorrhiza, and Artemisia. This bibliometric research helps increase public attention to the importance of consuming this natural substance which has been proven to be beneficial in research. The results of this bibliometric research indicate that this topic is still new and has not been widely researched, but has the potential to overcome several problems such as neuroprotective effects, oxidative stress, and mitochondrial pathway signalling.\n\nCurrently, people are increasingly aware of the importance of natural neurotrophic agents in maintaining brain health and performance. The results of bibliometric research show that names such as Panax notoginseng with ginsenoside, Huperzine A, Berberine, Curcumin, Salvia miltiorrhiza, and Artemisia receive quite high attention from the public. The existence of research that supports the benefits of these natural ingredients makes them the main preference as a safer and more natural alternative to medicine. Public attention to natural neurotrophic agents is growing, along with increasing awareness of the importance of brain health and a better quality of life.\n\nBibliometric research has revealed various benefits of natural neurotrophic agents based on qualitative and quantitative analysis. These studies show that Panax notoginseng with ginsenoside, humperzine A, berberine, curcumin, Salvia miltiorrhiza, and Artemisia has neuroprotective effects and can reduce oxidative stress associated with neurodegenerative diseases. In addition, this natural neurotrophic agent is also associated with improving cognitive function, improving mood, and protecting against mitochondrial damage. These benefits are scientifically proven through bibliometric research and make this natural ingredient a promising option for improving brain health and reducing the risk of neurological disorders.\n\nBibliometric research reveals significant implications for the use of natural neurotrophic agents. The results of this research provide a strong scientific basis to support the use of natural neurotrophic agents in maintaining brain health and treating neurological disorders. The implications of this research can help health experts in developing more effective and natural treatment strategies. Apart from that, people can also explore the benefits of this natural ingredient to improve their overall quality of life. Thus, the results of this bibliometric research provide a positive impetus for the use and utilization of natural neurotrophic agents in clinical practice and prevention of brain diseases.\n\n\nConclusion\n\nNatural Agent Neurotropik is a natural substance that has the ability to influence the brain’s nervous system and peripheral nervous system. It has been extensively studied in the fields of medicine and veterinary medicine. Its main characteristics include neuroprotective effects, enhancing cognition, enhancing mood, and improving brain function on the cell level. It can be derived from various natural sources, such as herbs, spices, and herbal products.\n\nNatural Agent Neurotropik has several advantages over other natural agents in terms of energy production, brain biogenesis, and neuroprotection. It is also more soluble and comprehensible than other biological agents. Some of the natural agents include Panax notoginseng with ginsenoside, Huperzine A, Berberine, Curcumin, Salvia miltiorrhiza, and Artemisia.\n\nThe presence of these natural agents in the environment can help people consume them and benefit from the research. Ginsenosida, an active ingredient in Panax notoginseng, has been shown to have neuroprotective effects and improve brain function. Overall, Natural Agent Neurotropik is a valuable and relevant alternative to traditional medicine.\n\n\nAuthor contribution\n\nAYS conducts research, gathers data, performs statistical analysis, and produces discussions and conclusions. DAYS editing.\n\n\nEthical consideration\n\nThis study used secondary data retrieved from database that do not require approval from the Ethics Committee for research on humans. However, we followed the ethical principles recommended for analysis of this nature through respecting ideas and citations and referencing authors and their publications.",
"appendix": "Data availability statement\n\nFigshare: Natural agents that are neuroprotective against mitochondria: a bibliometric-based research mapping 1998–2024, from cells to mitochondria.\n\nDOI: https://doi.org/10.6084/m9.figshare.25921246.v1 246\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nOpen Science Framework: PRISMA-ScR checklist and flow chart: Natural agents that are neuroprotective against mitochondria: a bibliometric-based research mapping 1998–2024, from cells to mitochondria: https://doi.org/10.6084/m9.figshare.25940968.v1. 247\n\n\nReferences\n\nSalsabila SF, Aligita W, Mulyani Y: Review: Neuroprotective effect of herbal plant extracts against Parkinson’s disease. Jurnal Ilmiah Farmasi. 2021; 17(2): 198–209. Publisher Full Text\n\nLi L, Liu G: Protective effects of schisanhenol against oxygen free radical induced injury of rat cerebral mitochondria and synaptosomes. 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PubMed Abstract | Publisher Full Text\n\nHe Y, Wang F, Chen S, et al.: The Protective Effect of Radix Polygoni Multiflori on Diabetic Encephalopathy via Regulating Myosin Light Chain Kinase Expression. J. Diabetes Res. 2015; 2015: 484721.\n\nZhang Y, Li C-s, Wu C-j, et al.: Neuroprotective effect of Shenfu Injection (参附注射液) following cardiac arrest in pig correlates with improved mitochondrial function and cerebral glucose uptake. Chin. J. Integr. Med. 2014; 20(11): 835–843. PubMed Abstract | Publisher Full Text\n\nFan Y, Yang T, Zheng Q, et al.: Protective effect of tanreqing injection on axon myelin damage in the brain of mouse model for experimental autoimmune encephalomyelitis. J. Tradit. Chin. Med. 2014; 34(5): 576–583. PubMed Abstract | Publisher Full Text\n\nLi J, Ji X, Zhang J, et al.: Paeoniflorin attenuates Aβ25-35-induced neurotoxicity in PC12 cells by preventing mitochondrial dysfunction. Folia Neuropathol. 2014; 52(3): 285–290. PubMed Abstract | Publisher Full Text\n\nZhou YF, Li L, Feng F, et al.: Osthole attenuates spinal cord ischemia-reperfusion injury through mitochondrial biogenesis-independent inhibition of mitochondrial dysfunction in rats. J. Surg. Res. 2013; 185(2): 805–814. PubMed Abstract | Publisher Full Text\n\nHwang CK, Chun HS: Isoliquiritigenin isolated from licorice Glycyrrhiza uralensis prevents 6-hydroxydopamine-induced apoptosis in dopaminergic neurons. Biosci. Biotechnol. Biochem. 2012; 76(3): 536–543. PubMed Abstract | Publisher Full Text\n\nYang L, Ye CY, Huang XT, et al.: Decreased accumulation of subcellular amyloid-β with improved mitochondrial function mediates the neuroprotective effect of huperzine A. J. Alzheimers Dis. 2012; 31(1): 131–142. PubMed Abstract | Publisher Full Text\n\nMounsey RB, Teismann P: Mitochondrial dysfunction in Parkinson’s disease: pathogenesis and neuroprotection. Parkinson’s disease. 2010; 2011: 617472.\n\nLiu B, Zhang H, Xu C, et al.: Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons. Brain Res. 2011; 1375: 59–67. PubMed Abstract | Publisher Full Text\n\nReddy TP, Manczak M, Calkins MJ, et al.: Toxicity of neurons treated with herbicides and neuroprotection by mitochondria-targeted antioxidant SS31. Int. J. Environ. Res. Public Health. 2011; 8(1): 203–221. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLoh KP, Qi J, Tan BK, et al.: Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function. Stroke. 2010; 41(11): 2661–2668. PubMed Abstract | Publisher Full Text\n\nKones R: Parkinson’s disease: mitochondrial molecular pathology, inflammation, statins, and therapeutic neuroprotective nutrition. Nutr. Clin. Pract. 2010; 25(4): 371–389. PubMed Abstract | Publisher Full Text\n\nYang Y, Lu B: Mitochondrial morphogenesis, distribution, and Parkinson disease: insights from PINK1. J. Neuropathol. Exp. Neurol. 2009; 68(9): 953–963. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee CS, Kim YJ, Ko HH, et al.: Modulation of 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells by K (ATP) channel block. J. Neural. Transm (Vienna). 2007; 114(3): 297–305. PubMed Abstract | Publisher Full Text\n\nJung TW, Lee JY, Shim WS, et al.: Rosiglitazone protects human neuroblastoma SH-SY5Y cells against MPP+ induced cytotoxicity via inhibition of mitochondrial dysfunction and ROS production. J. Neurol. Sci. 2007; 253(1-2): 53–60. PubMed Abstract | Publisher Full Text\n\nZhang XN, Wang HH, Wang ZQ: Protective effect of icaritin on apoptosis of primarily cultured rat neurons induced by Abeta25-35 peptide. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2007; 36(3): 224–228. 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Syst. Agents Med. Chem. 2022; 22(3): 175–187. PubMed Abstract | Publisher Full Text\n\nLi HY, Wang J, Liang LF, et al.: Sirtuin 3 Plays a Critical Role in the Antidepressant- and Anxiolytic-like Effects of Kaempferol. Antioxidants (Basel, Switzerland). 2022; 11(10). Publisher Full Text\n\nWang W, Wang S, Liu Y, et al.: Ellagic Acid: A Dietary-Derived Phenolic Compound for Drug Discovery in Mild Cognitive Impairment. Front. Aging Neurosci. 2022; 14: 925855. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWu J, Han C, Cao X, et al.: Mitochondria targeting fluorescent probe for MAO-A and the application in the development of drug candidate for neuroinflammation. Anal. Chim. Acta. 2022; 1199: 339573. PubMed Abstract | Publisher Full Text\n\nWu AG, Yong YY, Pan YR, et al.: Targeting Nrf2-Mediated Oxidative Stress Response in Traumatic Brain Injury: Therapeutic Perspectives of Phytochemicals. Oxidative Med. Cell. Longev. 2022; 2022: 1015791.\n\nLiu X, Wang C, Liu W, et al.: Oral Administration of Silibinin Ameliorates Cognitive Deficits of Parkinson’s Disease Mouse Model by Restoring Mitochondrial Disorders in Hippocampus. Neurochem. Res. 2021; 46(9): 2317–2332. PubMed Abstract | Publisher Full Text\n\nTian SX, Cheng W, Lu JJ, et al.: Role of Militarine in PM(2.5)-Induced BV-2 Cell Damage. Neurochem. Res. 2021; 46(6): 1423–1434. PubMed Abstract | Publisher Full Text\n\nHong JY, Kim H, Lee J, et al.: Neurotherapeutic Effect of Inula britannica var. Chinensis against H(2)O(2)-Induced Oxidative Stress and Mitochondrial Dysfunction in Cortical Neurons. Antioxidants (Basel, Switzerland). 2021; 10(3).\n\nLi X, Wen W, Li P, et al.: Mitochondrial Protection and Against Glutamate Neurotoxicity via Shh/Ptch1 Signaling Pathway to Ameliorate Cognitive Dysfunction by Kaixin San in Multi-Infarct Dementia Rats. Oxidative Med. Cell. Longev. 2021; 2021: 5590745.\n\nXu H, Zhou W, Zhan L, et al.: The ZiBuPiYin recipe regulates proteomic alterations in brain mitochondria-associated ER membranes caused by chronic psychological stress exposure: Implications for cognitive decline in Zucker diabetic fatty rats. Aging. 2020; 12(23): 23698–23726. PubMed Abstract | Publisher Full Text | Free Full Text\n\nErukainure OL, Salau VF, Bharuth V, et al.: Hyperglycemia alters lipid metabolism and ultrastructural morphology of cerebellum in brains of diabetic rats: Therapeutic potential of raffia palm (Raphia hookeri G. Mann & H. Wendl) wine. Neurochem. Int. 2020; 140: 104849. PubMed Abstract | Publisher Full Text\n\nPradhan P, Majhi O, Biswas A, et al.: Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model. Cell Death Dis. 2020; 11(9): 739. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNan L, Xie Q, Chen Z, et al.: Involvement of PARP-1/AIF Signaling Pathway in Protective Effects of Gualou Guizhi Decoction Against Ischemia-Reperfusion Injury-Induced Apoptosis. Neurochem. Res. 2020; 45(2): 278–294. PubMed Abstract | Publisher Full Text\n\nXu Y, Zhi F, Mao J, et al.: δ-opioid receptor activation protects against Parkinson’s disease-related mitochondrial dysfunction by enhancing PINK1/Parkin-dependent mitophagy. Aging. 2020; 12(24): 25035–25059. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGu C, Li L, Huang Y, et al.: Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy. Oxidative Med. Cell. Longev. 2020; 2020: 3549704.\n\nKandezi N, Mohammadi M, Ghaffari M, et al.: Novel Insight to Neuroprotective Potential of Curcumin: A Mechanistic Review of Possible Involvement of Mitochondrial Biogenesis and PI3/Akt/GSK3 or PI3/Akt/CREB/BDNF Signaling Pathways. Int. J. Mol. Cell. Med. 2020; 9: 1–32. PubMed Abstract | Publisher Full Text\n\nLi R-L, Zhang Q, Liu J, et al.: Hydroxy-α-sanshool Possesses Protective Potentials on H2O2-Stimulated PC12 Cells by Suppression of Oxidative Stress-Induced Apoptosis through Regulation of PI3K/Akt Signal Pathway. Oxidative Med. Cell. Longev. 2020; 2020: 3481758.\n\nQuan Y, Ma A, Yang B: Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Brain Injury. Adv. Exp. Med. Biol. 2019; 1182: 159–180. PubMed Abstract | Publisher Full Text\n\nWang Y-J, Wang X-Y, Hao X-Y, et al.: Ethanol Extract of Centipeda minima Exerts Antioxidant and Neuroprotective Effects via Activation of the Nrf2 Signaling Pathway. Oxidative Med. Cell. 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Brain Mitochondria: Distribution and Function. 2019; pp. 157–208.\n\nSaleh AY, Saputra DAY: Figshare: Natural agents that are neuroprotective against mitochondria: a bibliometric-based research mapping 1998–2024, from cells to mitochondria.2024. Publisher Full Text\n\nSaleh AY, Saputra DAY: Open Science Framework: PRISMA-ScR checklist and flow chart: Natural agents that are neuroprotective against mitochondria: a bibliometric-based research mapping 1998–2024, from cells to mitochondria.2024. Publisher Full Text\n\nvan Eck NJ , Waltman L: Citation-based clustering of publications using CitNetExplorer and VOSviewer. Scientometrics. 2017; 111(2): 1053–1070. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "314755",
"date": "18 Sep 2024",
"name": "Brijesh Kumar Singh",
"expertise": [
"Reviewer Expertise Neurodegenerative diseases and gene 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\nThe study employed a systematic literature review to gather and analyze data on natural agents and their neuroprotective effects on mitochondria. The Scopus database was utilized with specific search terms, including \"natural agents,\" \"herb*,\" \"neuroprotective,\" and \"mitochondria.\" The collected data were processed using Biblioshiny and VOSviewer, widely used tools for bibliometric analysis. These tools facilitated the visualization of research trends, identification of key documents, and mapping of influential contributors in the field. Two types of analyses were performed. The first was a quantitative analysis, which examined publication trends, citation patterns, and contributions from different authors and countries, providing insights into the field’s growth over time and identifying the most influential works. The second was a qualitative analysis, which explored the thematic content of the literature and examined emerging research clusters related to natural neuroprotective agents. This approach helped uncover major themes and focal areas within the field, providing a clearer view of the evolving research landscape on mitochondria and neuroprotection. The literature review revealed several key trends in studies focusing on natural agents that target mitochondrial function for neuroprotection. One significant trend was the increasing number of publications each year, reflecting growing interest in the topic. Additionally, several highly cited papers were identified, highlighting their importance to the field. Journals like Neurobiology of Aging and Frontiers in Neuroscience were noted as key sources for disseminating research findings. The analysis also identified the leading contributors to the field, with researchers from the United States, China, and Germany making notable contributions. Network visualizations and cluster analyses, performed using VOSviewer, identified major research clusters centered on themes such as neuroprotection, mitochondrial dysfunction, oxidative stress, and herbal medicine. Thematic maps and evolution analysis showed a shift from foundational research on mitochondrial dysfunction to a focus on natural agents as potential therapeutic interventions. Additionally, word cloud analysis highlighted keywords like \"mitochondria,\" \"herb,\" \"neuroprotection,\" \"oxidative stress,\" and \"brain function,\" emphasizing their importance in the literature. The findings support growing evidence that Natural Agent Neurotropik, a group of natural compounds derived from herbs, spices, and other plant sources, holds significant potential as a neuroprotective agent. These natural agents enhance mitochondrial function, improve energy production, promote neurogenesis, and protect against oxidative stress, offering a novel approach to slowing the progression of neurodegenerative diseases. Furthermore, they tend to have fewer side effects than synthetic drugs, making them a safer option for long-term use in promoting brain health. This work underscores the need for continued research on natural agents targeting mitochondria for neuroprotection, particularly in the context of developing new therapies for neurodegenerative disorders. Integrating traditional medicinal knowledge with modern scientific techniques offers great promise in discovering effective treatments that may help prevent or delay the onset of these diseases. To improve the quality of this article, several additional steps could be taken-\n\nThe article could address the challenges of standardization in natural agents, as variability in composition can affect reproducibility across studies. Including information on the importance of proper characterization, standardized extraction methods, and dosage consistency for these natural compounds would improve the scientific rigor of the article. Discussing the long-term safety and potential toxicity of these natural agents, particularly when used in higher doses or over extended periods, would enhance the article. Incorporating data or discussing the need for such studies would provide a more balanced view of the potential risks versus benefits. A comparative analysis of the efficacy of natural agents versus synthetic drugs in terms of neuroprotection and mitochondrial function would provide more context and emphasize the advantages or limitations of natural treatments. This could also be an opportunity to discuss potential synergistic effects between natural and synthetic agents.\nThese additions would make the article more comprehensive, rigorous, and aligned with current scientific practices, ultimately improving its overall quality and impact in the field of neuroprotection and mitochondria research.\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? Yes\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? Not applicable\n\nAre the conclusions drawn adequately supported by the results presented in the review? Yes\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Yes",
"responses": [
{
"c_id": "12487",
"date": "23 Oct 2024",
"name": "ARMAN YURISALDI SALEH",
"role": "Author Response",
"response": "Thank you to the reviewers for their kindness in providing feedback and suggestions. Natural agents have compositional heterogeneity that can influence reproductive results across several studies. Consequently, it is essential to conduct adequate characterization and employ standardized extraction techniques. Precise characterisation entails identifying active components and establishing the chemical profile of plant extracts. Chromatographic techniques, such as *High-Performance Liquid Chromatography (HPLC)* and *Gas Chromatography (GC), can be employed to identify and quantify active chemicals in plant extracts. Furthermore, spectroscopic techniques such as *Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR) Spectroscopy are applicable for the characterization of substances. Conventional extraction techniques, including maceration, percolation, and Soxhlet extraction, must be employed to guarantee uniformity in the extract's composition. Maceration entails immersing plant material in a solvent at ambient temperature, whereas percolation consists of the solvent traversing through the plant material. Soxhlet extraction use hot solvent to isolate active chemicals from plant material. Employing a standardized extraction procedure will guarantee that the resultant extract possesses a homogeneous composition. Furthermore, dose consistency is crucial to guarantee that the doses employed in research are standardized and replicable. Inconsistent dosing may result in disparate outcomes and complicate the comparison of findings across several research. Consequently, it is essential to ascertain the suitable dosage based on prior preclinical and clinical studies. The long-term safety and potential toxicity of natural agents should be evaluated, particularly when administered in elevated doses or over prolonged durations. Certain natural substances may exhibit adverse side effects or toxicity when administered in elevated concentrations. Certain natural chemicals may induce hepatic or renal damage when administered in high quantities. Consequently, it is essential to undertake additional study to assess the long-term safety of these natural agents. Data from toxicological studies and clinical trials can yield more extensive insights into the potential risks and advantages of utilizing natural substances. Toxicology study entails the examination of chemicals on laboratory animals to ascertain safe dosage levels and those that induce hazardous effects. Clinical studies entail the assessment of substances on human subjects to determine their safety and efficacy. This research provides data to establish a safe and effective dosage for prolonged use. An analysis comparing the performance of natural medicines with synthetic pharmaceuticals regarding neuroprotection and mitochondrial function helps elucidate the benefits and drawbacks of natural therapy. Natural agents typically have a superior safety profile and a reduced incidence of side effects in comparison to synthetic pharmaceuticals. Natural substances like curcumin and resveratrol exhibit neuroprotective properties with little adverse consequences. Nevertheless, synthetic medications such as memantine and ketamine may exhibit more success in the treatment of neurodegenerative illnesses; yet, they may also result in more severe adverse effects. Comparative investigations utilizing in vitro and in vivo methodologies can yield profound insights into the distinctions between natural medicines and synthetic pharmaceuticals regarding neuroprotection and mitochondrial function. In vitro tests entail evaluating chemicals on cells produced in a laboratory setting, whereas in vivo tests involve assessing compounds on laboratory animals. This study's results can identify the merits and demerits of each therapy kind. The integration of natural agents with synthetic pharmaceuticals can offer a more comprehensive and efficacious strategy for neuroprotection and mitochondrial function. This combination can utilize the benefits of both agent types, specifically the superior safety profile of natural agents and the enhanced efficacy of synthetic medications. The combination of curcumin and memantine can augment neuroprotective effects by mitigating the adverse effects associated with the use of memantine in isolation. Studies indicate that the amalgamation of natural and synthetic medicines can augment therapy efficacy and diminish the necessary dosage to attain the desired therapeutic outcomes. Moreover, this combination may reduce the likelihood of drug resistance, which frequently arises from prolonged usage of synthetic pharmaceuticals. Republic of Indonesia Food and Drug Supervisory Agency, 2023. Consequently, it is essential to undertake more study to assess the efficacy of integrating natural and synthetic medicines in neuroprotection and mitochondrial function."
}
]
}
] | 1
|
https://f1000research.com/articles/13-754
|
https://f1000research.com/articles/11-1401/v1
|
29 Nov 22
|
{
"type": "Research Article",
"title": "Molecular survey of certain protozoan agents that cause diarrhea in children in Sudan",
"authors": [
"Mosab Adam",
"Hongwei Shen",
"Khalid-A Enan",
"Hao Wang",
"Azza B. Musa Musa",
"Abdel R. El Hussein",
"Isam M. Khidir",
"Xuejun Ma",
"Hongwei Shen",
"Khalid-A Enan",
"Hao Wang",
"Azza B. Musa Musa",
"Abdel R. El Hussein",
"Isam M. Khidir",
"Xuejun Ma"
],
"abstract": "Introduction Diarrhea is a significant health problem in third world countries; identification of causative agents of diarrhea is essential to apply measures to prevent and control this disease. In addition, scant data are available regarding childhood diarrhea in Sudan. Our research aimed to determine the incidence of specific protozoan pathogens (Entameobia histolytica, Cryptosporidium spp., and Gardia lambelia) among the young (aged less than five years) in Khartoum, Sudan. Methods We conducted a parasitological cross-sectional survey, and stool samples from 437 patients were examined for E. histolytica, C. parvum, and G. lambelia using a multiplex real-time PCR method. Results Of the 437 stool samples tested, infection with intestinal parasite was found in 155 (35.5%) cases, and co-infection was identified in 16 (3.7%) cases. G. lambelia (18.8%) and C. parvum (15.8 %) were the most frequently identified parasites, followed by E. histolytica (0.5%). The highest and lowest rates of parasitic infections were seen in the less than two years age group (32.7%), and in the 2–4-year-old group (2.7%), the male children showed higher rates of infections (23.7%) compared to females (11.7%). The incidence of protozoan infection was higher (37.7%) in the rainy season (August to December) (32.7%) in contrast with that (2.7%) in the dry season (April to June). Discussion Our present study demonstrated the high prevalence of G. lambelia and C. parvum in children with diarrhea in Khartoum State and the multiplex real-time technique's usefulness in disclosing pathogenic protozoal agents. Our result highlighted the necessity of developing intervention measurement and control strategies to deal with childhood parasitic diarrhea in this region.",
"keywords": [
"Diarrhea",
"Detection",
"Parasitic",
"Protozoan",
"Pathogens",
"Childhood"
],
"content": "Introduction\n\nDiarrhea is defined as passing soft, loose, or watery feces three times or more in 24 hours; it is usually a result of the consumption of pathogen-contaminated water or food.1,2 Diarrhea remains a major cause of mortality and morbidity in children in third-world countries.1,3–5 More than 1 billion episodes of diarrhea occur annually, resulting in approximately 2.5 million deaths in children aged less than 5 years in developing countries.1,2,5,6 Where diarrhea is considered the third most common cause for young children to visit health centers, some of the underlying conditions found in the community of most developing countries, including malnutrition and poor hygiene, may increase the risk of experiencing diarrheal disease.2 In developed countries, the availability of modern technologies and suitable water supply has led to a decline in global death due to diarrhea; however, despite the substantial effort to supply modern technology and management practices, diarrhea in Africa is still unacceptably ranked as the second cause of death among young children.1,7–9 Despite the high morbidity of childhood diarrhea in Sudan, the knowledge of the parasitic causative agents is scant. Parasitic protozoans that infect the intestinal tract in developing countries include Cryptosporidium spp., G. lambelia, and E. histolytica the agents that cause cryptospordiasis, giardiasis, and amoebiasis respectively, which are considered prime for diarrheal diseases in children under 5 years old.15 The limited specificity and sensitivity of the microscopic method commonly used in most laboratories in Sudan decreased the detection rate of parasitic infections. As a result, there is little information about the precise incidence of diarrhea and causative protozoan agents.\n\nThis study aimed to explore the incidence of some protozoan organisms (Cryptosordium parvum, Giardia lambelia, Giardia lambelia, and Entameobia histolytica) that produce acute diarrheal illness among young children using molecular techniques.\n\n\nMethods\n\nThis cross-sectional study was co-conducted at the Central Laboratory, Ministry of Higher Education and Research, Sudan, and the National Institute for Viral Disease Control and Prevention, China Center for Disease Control and Prevention, China (CDC), Beijing, China. A total of 437 fecal samples (one per patient) comprising 276 boys and 161 girls, who mostly live in a rural area, were collected in a dry, clean plastic container during two different seasons (the hot, dry season from April to June, and the rainy season from August to December) in the year 2014 at Khartoum teaching hospitals. The stool specimens were kept at −20°C until tested at the beginning of 2015. The frozen samples were then transported on dry ice to the China CDC, Beijing, China. Children admitted to hospitals had been clinically diagnosed with acute diarrhea ranging from 1 to 4 days before the sample collection. The participants were aged ≤2 years (403, 92.2%); >2–≤4 years (32, 7.3%), and >4–˂5 years (2, 0.5%). Patient data were collected through a structured questionnaire, including age, gender, and season. The study was approved by the ethical committee of the Sudan Academy of Sciences (Approval number (2367) and informed written permission was obtained from the parents or guardians of the enrolled children.\n\nParasite DNA was extracted from 200 μL of 10% fecal suspension prepared in phosphate buffer saline using QIAamp® Fast DNA Stool Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s instructions. The extracts were eluted in 60 μL of DNase-free water, immediately aliquoted in 20 μL, and kept at −80°C.\n\nPrimers and probes of multiplex real-time PCR\n\nA total of three primer pairs and three probes for the simultaneous detection of E. histolytica, C. parvum, and G. lamblia were used.10 Table 1 shows the oligonucleotides sequence of the primers, probes and target genes, and amplicon sizes.\n\nThe nucleotide primers and probes for multiplex real-time PCR used in this study\n\na SSU rRNA, small subunit ribosomal RNA.\n\nb F, forward; R, revers.\n\nMultiplex real-time PCR\n\nReal-time PCR was performed with a Multiplex PCR kit (Qiagen, Hilden, Germany) in a 20 μL volume containing 6.25 pmol of each E. histolytica-specific primers, 6.25 pmol of each G. lamblia-specific primers, 25 pmol of each C. parvum-specific primers, 1.75 pmol of E. histolytica-specific VIC-TaqMan probe, 2.5 pmol of G. lamblia-specific FAM-TaqMan probe, 8.75 pmol of C. parvum-specific Texas Red-TaqMan probe. Amplification consisted of 15 min at 95°C, 40 cycles of 15 s at 95°C, 30 s at 60°C, and 30 s at 72°C. The iCycler real-time detection system (Bio-Rad) performed amplification, detection, and data analysis.\n\n\nResult\n\nA potential protozoal parasite was diagnosed in 155/437 (35.5%) cases, among which the highest prevalence was G. lamblia (82/437, 18.8%), followed by Cryptosporidium spp. (69/437, 15.8%), and E. histolytica (4/437, 0.5%) (Figure 1). The highest rate of parasitic infection was seen in the ≤2 years group (32.7%) and much lower in the >2–≤4 years old group (2.7%) (Table 2). In contrast, the protozoal parasite was not detected in the age group of >4–˂5 years. Among children with parasitic infections, 23.7% were male, while 11.7% were female (Table 3). As much more samples were collected from boys (276) than from girls (161) in the age group ≤2 years (403, 92.2%), the comparisons between these variables were not relevant. The incidence of protozoan parasitic infection was higher in the rainy season (August to December) than in the dry season (April to June) (32.7% and 2.7%, respectively) (Table 4).\n\nInfection with one type of parasite was found in 139 cases (31.8%), while parasite co-infection was detected in 16 patients (3.7%), which involved E. histolytica and G. lambelia in two cases, and G. lamblia and Cryptosporidium spp. in 14 cases (Table 5).\n\n\nDiscussion\n\nGastrointestinal protozoan parasites are still posing common health problems, mainly in children aged less than 5 years worldwide. The rapid and accurate identification of protozoan parasites is a big challenge in many developing countries. The real-time multiplex PCR technique that provides concurrent detection of all protozoal parasites used herein was an exceedingly powerful laboratory system, enabling rapid, sensitive, precise, and inexpensive parasite detection.\n\nThis study was conducted during two seasons (autumn and summer), from April to December 2014, in Khartoum State, Sudan. The present study aimed to determine the prevalence of certain protozoan parasites linked with acute gastroenteritis in stool samples from children less than 5 years old using a multiplex real-time PCR assay developed in a previous study.10\n\nAmong the 437 fecal specimens examined, 276 were collected from male children and 161 from females, amounting to a male-to-female ratio of 1:1.7. Most of the samples were from less than ≤2 years old (403, 92.2%), followed by >2–≤4 years (32, 7.3%) and >4–˂5 years (2, 0.5%).\n\nAs they showed in Table 2, the gender distribution among the G. lambelia-positive samples was 14.2% in males and 4.6 % in females (P<0.01), indicating a statistically significant difference among the gender group that supports the statement of Khwam H.11\n\nThe most significant number of samples were from the age group ≤2 years (403, 92.2%), followed by >2–≤4 years (32, 7.3%) and >4–˂5 years (2, 0.5%). The result of our study indicates the highest prevalence of protozoal diarrhea (32.7%) was detected in the age group of ≤2 years flowed by >2–≤4 years (2.7%), and no protozoan pathogen was found in the age group of >4–˂5 years; however, these results could be explained by the fact that most of our samples were collected from the age group ≤2 years in which the decline of the maternal immunity with an age risk factor of diarrhea infection.4,12 The highest number of positivity was detected in the samples of boys less than two years old. The reason for the bias in the numbers of children with diarrhea (boys of ≤2 years) admitted to hospitals is not clear and needs to be further investigated to determine whether or not it is the pattern of childhood diarrhea in Sudan. The contaminated hands and bad hygiene may contribute to the transmission of food borne infection in these children, which was in agreement with the investigation in Nepal, where the highest prevalence of parasitic diarrhea was found in the age group of fewer than two years.13 But our result differed from another study in Khartoum13 in which the major group of infections was in >4–˂5 years old children, and this may again be due to statistical bias because most of our samples were collected from the age group of ≤2 years; This should be avoided in future studies by equalizing the age group of the study or by using a larger sample size.\n\nThe result revealed a higher prevalence (35.5%) of protozoan diarrhea disease compared with other studies conducted in Khartoum state (16%).14 and in other developing countries, including Nepal and Ethiopia (0.7%, 15.6%, respectively).13,15 In comparison, the incidence was lower than that in Tanzania and South Africa (55.6%, 68%, respectively)5,16 and close to that reported in the Gaza strip (39%).17 To our knowledge, our study is the first to demonstrate a high prevalence of Cryptosporidium (15.8%) in Sudan. The diagnosis of Cryptosporidium used to depend on the Ziehl−Neelsen stain, and it was neglected mainly by our laboratories until we used a sensitive molecular assay that increased the detection rate of these agents.\n\nThe most prevalent protozoan detected in the present investigation was G. lamblia, with a prevalence of 18.8%, which is higher than in the study conducted in Khartoum State (15.8%).14 Its prevalence was followed by Cryptosporidium spp. (15.8%) and E. histolytica (0.9%). This result was consistent with previous findings in developing countries, including India, Gaza and Nigeria4,17,18 Infection with a single protozoan parasite was found in 139 cases (31.8%) cases; co-infection was found in 16 cases (3.7%). The study of co-infection on clinical severity was not studied in these patients. However, it has been reported that no significant variation was reported in the clinical symptoms of patients with co-infections compared with those with single infections.19 Our study showed that the incidence of a protozoan parasite is higher in autumn (wet) than that in summer (dry), which was in accordance with the study conducted in Khartoum state.14 It should be noted that no protozoan pathogen was detected in 282 stool samples (64.6%) which were likely due to infections with other pathogens like viruses and bacteria and also may be due to noninfectious reasons like hypersensitivity to certain food ingredients and weaning diarrhea that result of the inability of an underdeveloped child intestine to metabolize the food. Poor hygiene and sanitation and lack of proper toilets may facilitate these infections.\n\nThe present study furnished some crucial insights into the protozoan cause of child diarrhea in Khartoum State. Findings of this study will certainly help us understand the importance of parasitic diarrhea in younger than five years of children, and these findings are valuable in developing measures to improve the health condition of the young children. Furthermore, this study calls for the establishment of sensitive and specific molecular techniques, such as multiplex PCR, for the detection of the protozoan pathogen in a clinical setting.\n\n\nAuthors contributions\n\nMosab, Isam, and Xuejun designed the experiment; Mosab and Hong-do the lab experiment; Azza analyzed the data; Mosab, Khalid, and Abdel collected the samples. Mosab Hong and Abdel wrote the article.",
"appendix": "Data availability\n\nFigshare: Underlying data for “Molecular survey of certain protozoan agents that cause diarrhea in children in Sudan”, https://doi.org/10.6084/m9.figshare.21201676.v3. 20\n\nThis project contains the following underlying data:\n\n• Data information.xlsx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nKhalil I, Colombara D, Forouzanfar M, et al.: Burden of Diarrhea in the Eastern Mediterranean Region, 1990 2013: Findings from the Global Burden of Disease Study 2013. Am. J. Trop. Med. Hyg. 2016; 6(95): 1132–1319.\n\nVargas M, Gascon J, Casals C, et al.: Etiology of diarrhea in children less than five years of age in Ifakara, Tanzania. Am. J. Trop. Med. Hyg. 2004; 70(5): 536–539. PubMed Abstract | Publisher Full Text\n\nDean TJFR, Makgoba MW, Bos ER, et al.: Disease and mortality in sub-Saharan Africa.2nd ed.2006.\n\nGupta DA: Study of the prevalence of diarrhea in children under the age of five years: its association with wasting. Indian J. Sci. Res. 2014; 7(1): 1315–1318.\n\nNgosso BEN, Namkinga G: Identification of Pathogenic Intestinal Parasitic Protozoa Associated with Diarrhea among Under-fives Children in Dar Es Salaam, Tanzania. Int. J. Med. Med. Sci. 2015; 2(4): 49–55.\n\nChen J, Tang J, Liu J, et al.: Development and evaluation of a multiplex PCR for simultaneous detection of five foodborne pathogens. J. Appl. Microbiol. 2012; 112(4): 823–830. PubMed Abstract | Publisher Full Text\n\nQuin A: Diarrhea likelihood in Ghanaian children: A Study of the Association between Diarrhea and Water and Sanitation Infrastructure. Master thesis of Public Policy in the Georgetown Institute.2009; p. 74.\n\nMichael HMM, Cleveland C: Water pollution. Encyclopedia of Earth, National Council for Science and the Environment.2010.\n\nOrganization WH: The world health report 2005—Make every mother and child count. Geneva, Switzerland:WHO Press;2013.\n\nVerweij JJ, Blange RA, Templeton K, et al.: Simultaneous detection of Entamoeba histolytica, Giardia lamblia, and Cryptosporidium parvum in fecal samples by using multiplex real-time PCR. J. Clin. Microbiol. 2004; 42(3): 1220–1223. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhwam H, Hayat D, Abdul M: Parasitic infections causing diarrhoea among children less than six years at Al-Nasiriya province. J. Uni. Thi-Qar. 2016; 4(11): 134–142.\n\nSherchand B, Yokoo M, Sherchand O, et al.: Burden of Enteropathogens Associated Diarrheal Diseases in Children Hospital, Nepal. Sci. World. 2010; 7(7): 71–75. Publisher Full Text\n\nShamshul A, Keshab P, Bharat Mani P, et al.: Pattern of Acute Parasitic Diarrhea in Children Under Five Years of Age in Kathmandu, Nepal. Open J. Med. Microbiol. 2012; 02: 95–100. Publisher Full Text\n\nSaeed A, Abd H, Sandstrom G: Microbial etiology of acute diarrhea in children under five years of age in Khartoum, Sudan. J. Med. Microbil. 2015; 64(4): 432–437. PubMed Abstract | Publisher Full Text\n\nFirdu T, Abunna F, Girma M: Intestinal Protozoal Parasites in Diarrheal Children and Associated Risk Factors at Yirgalem Hospital, Ethiopia: A Case-Control Study. Int. Sch. Res. Notices. 2014; 2014: 1–8. Publisher Full Text\n\nSamie A, Guerrant RL, Barrett L, et al.: Prevalence of intestinal parasitic and bacterial pathogens in diarrhoeal and non-diarrhoeal human stools from Vhembe district, South Africa. J. Health Popul. Nutr. 2009; 27(6): 739–745. PubMed Abstract\n\nMezeid N, Shaldoum F, Al-Hindi AI, et al.: Prevalence of intestinal parasites among the population of the Gaza Strip, Palestine. Ann. Parasitol. 2014; 60(4): 281–289. PubMed Abstract\n\nC.M.U1 A, OAN, CUN: Etiology of Acute Diarrhoea Among Children In Owerri, Imo State Nigeria. App. Sci. Rep. 2015; 10(3): 128–132.\n\nSaikruang W, Khamrin P, Suantai B, et al.: Detection of diarrheal viruses circulating in adult patients in Thailand. Arch. Virol. 2014; 159(12): 3371–3375. PubMed Abstract | Publisher Full Text\n\nAdam M, Du H, Enan KA, et al.: Molecular survey of certain protozoan agents that cause diarrhea in children in Sudan. figshare.2022. Publisher Full Text"
}
|
[
{
"id": "160656",
"date": "15 Feb 2023",
"name": "Luther A Bartelt",
"expertise": [
"Reviewer Expertise Infectious diseases",
"intestinal protozoa epidemiology and pathogenesis",
"malnutrition",
"microbiota"
],
"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 investigators report on the findings of 3 protozoans in children under 5 that were hospitalized for acute diarrhea. It is always helpful to have surveillance data for difficult to detect pathogens using molecular methods from a wide range of global sites. The report is therefore helpful in contributing data to improved understanding of local patterns of these globally distributed parasites.\n\nThe limitations, which the authors need to better explain, include a limited number of demographics variables (resulting in an inability to control for possible confounders that lead to a finding of a difference between M vs F Giardia status for example), the lack of reporting of statistical methods, the lack of reporting of PCR validation steps and whether any biomass or molecular method was used to standardize the DNA extraction, and the lack of a comparator of conventional-based diagnostics that would greatly enhance the differential sensitivity of the molecular methods (as it is one cannot discern if the difference in Cryptosporidium spp. reported in this study compared with others in Sudan as raised in the discussion is due to difference in diagnostic tools or difference in study population).\nAlso, the title is misleading. The study population appears to be children who were hospitalized for acute diarrhea. This population is different from a population consisting of diarrhea of any severity. We recommend the title be modified to better reflect the population studied: Molecular prevalence of three intestinal protozoa in young children hospitalized for acute diarrhea in rural Sudan. If this is a population of children with moderate-to-severe diarrhea (was there any tool to assess diarrhea severity other than hospitalization?), then the discussion should address and cite other studies specific to this acutely ill population.\n\nGeneral:\nSpelling and grammar need to be reviewed throughout. For example, \"lambelia\" and Entameobia are wrong. For example, in the results section, should 'the comparisons between these variables were not relevant' read 'the comparisons...were not statistically significant'? It is not accurate to claim a comparison is irrelevant. Please clarify, or change all references to specific Cryptosporidium species to Cryptosporidium spp. (or show specific sequencing results that were used to determine the specific species).\n\nAbstract:\n\nPlease provide consistent reporting in the results section. The N (%) notation as in the first sentence should be reported for all.\n\nMethods:\nPlease include validation methods for the triple-plex PCR (eg. were there positive controls)? Is there conventional diagnostic data to accompany the PCR results? How did the team decide to dilute all fecal specimens into 10% saline? Was anything done to normalize the amount of fecal material at baseline (some diarrheal samples may already me more 'dilute' than others). QIAmp DNA stool extraction kits may be suboptimal for DNA extraction. Were any steps taken to enrich DNA from parasite (oo)cysts (for example, freeze-thaw and/or bead beating)?\nFor improved clarity, please organize with the following additional sections:\n\nEthical consideration Study area and participants Sample collection and storage Nucleic acid extraction (already present) PCR amplification and parasite detection (already present). Statistical analysis (this is currently missing entirely)\nResults:\n\nPlease provide a table with the demographics data for all variables recorded from the questionnaire. As in the abstract, please include N (%) notations for all reported results for consistency. Please apply consistent use of a) gender-specific terms (male and female rather than flipping to 'boys and girls'), b) seasonality (hot-dry vs rainy rather than flipping to summer vs autumn in the discussion). The PCR reported does not appear to be specific for Cryptosporidium parvum (as claimed in the abstract). Please clarify what \"1\" and \"2\" mean in the source data and why some columns are incomplete and why some text is red and other text is black.\nDiscussion:\n\nPlease expand on the importance of the finding of M vs F differences in G lamblia positivity, and in context with other published literature. Only one citation is used here, and little is articulated about the statement of \"Kwam H.\" Important questions here would relate to exposure risks versus some other reason why male and female children would have different susceptibilities to infection. Please clarify this statement: \"due to noninfectious reasons like hypersensitivity to certain food ingredients and weaning diarrhea that result of the inability of an underdeveloped child intestine to metabolize the food\". What are the clinical/treatment implications of finding 35% prevalence of these 3 protozoa in children hospitalized in rural Sudan?\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "179572",
"date": "26 Jul 2023",
"name": "Monira Sarmin",
"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 is an important study,\nWrite up needs a lot of improvement. Introduction is well written. However other sections need care especially the discussion, results were repeated many a times.\nI am adding my observations:\nMethods:\n\nDuration of the study?\n\nHow the sample size 437 were fixed? Did you calculate the sample size?\n\nWhat was the sampling methods?\n\nDid you enroll all children? Please add a study flow diagram.\n\nWhat were the eligibility criteria?\n\nDescription of the study site might help the reader to gasp the scenario.\n\nIs Jan- March winter season? Why excluded?\n\nMethods section also need a description of the statistical analysis. Which analytical tools were used for data analysis?\n\nNeeds discussion with a statistician.\nResults:\nUsually a pie chart consists of 100%, though there is a label of 18.8, visually it is >50%, So, the figure 1 needs to corrected. You can build a pie of pie or bar of pie instead.\n\nTable 4 indicates season as Autumn and summer, there is no elaboration in the method. Rather, it was labelled as dry and rainy seasons. Do they differ?\n\nDid you collect only data on age, sex, season?\n\nTheir nutritional status, socio-economic condition, vaccination, housing, water supply Presence/absence of comorbidities, other laboratory analysis, outcome of this admission also needs to be incorporated.\n\nPatient data were collected through a structured questionnaire, including age, gender, and season. This statement needs modification. We collect data on biological sex, not on gender. There is difference between sex and gender.\n\nAs much more samples were collected from boys (276) than from girls (161) in the age group ≤2 years (403, 92.2%), the comparisons between these variables were not relevant.—This statement is not correct, proportion is the most important indicator. And in the result section, we should only present the results. We have discussion section to accept or refute the results.\n\nDid your facility receive more male child, or you have included more male children? What is the national proportion?\n\nTable 2,3,4 could be merged to a single table- column containing the name of parasite and rows containing the distribution of age, sex, season and etc.\n\nDiscussion:\nThe highest rate of parasitic infection was seen in the ≤2 years group (32.7%) and much lower in the >2–≤4 years old group (2.7%) (Table 2). In contrast, the protozoal parasite was not detected in the age group of >4–<5. Why it happened? What is your explanation?\n\nThis study was conducted during two seasons (autumn and summer), from April to December 2014, however, in methods, July was not included.\n\nmale-to-female ratio of 1:1.7, this result first appeared in the discussion section, but it should be come in the result section first.\n\nIf maternal immunity is an important factor against parasitic infection, then it is assumed that older children had more parasitic infection than younger children, but this study did not find that.\n\nA limitation section should be added.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? 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? Partly\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "10962",
"date": "22 Mar 2024",
"name": "Mosab Adam",
"role": "Author Response",
"response": "Thanks for these informative comments ts really raise up our manuscript We took all reviewer comments, made corrections throughout the paper, and updated this version. 1. rewrote the abstract section and updated it according to the reviewer's suggesting 2. we update the introduction section by rewriting the updated information, adding new updated references, and deleting the old ones 3. rewrote the method section, added the missing information, and updated carefully with the help of reviewers' comments 4. rewrote the result section, updated and classified it as the subtitle, added the statistical part, updated the tables and the diagram 5. update the discussion section and address the reviewer's comments"
}
]
},
{
"id": "179577",
"date": "01 Aug 2023",
"name": "Jean Bernard Lekana-Douki",
"expertise": [
"Reviewer Expertise Epidemiology of Infectious 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\nThe article titled ‘Molecular survey of certain protozoan agents that cause diarrhea in children in Sudan” by Mosab Adam et al. described the identification of three main intestinal protozoan parasite (Cyptosprodium parvum, Giardia lamblia and Entamoeba histolytica) in Sudan. While the paper has merit, there are a few major challenges with the paper in the current format:\nPage 1 (of the pdf version of the article): Abstract Introduction: Changed ‘’aged less than five years” by ‘’children”. Changed “Cryptosporidium spp.” by “Cryptosporidium parvum” and “Giardia lambelia” by “Giardia lamblia”.\nMethods: This section isn’t sufficiently clear and precise. Please make the necessary changes. For example, you might say: “We conducted a cross-sectional survey among children under five years of age hospitalized with acute diarrhea between April to December 2014. Diarrheal stool samples were collected and examined for E. histolytica, C. parvum and G. lamblia using a multiplex real-time PCR method”. The number of children included in the study must appear in the results section.\nResults: Please make the necessary changes. For example, you might say: “A total of the 434 acute diarrheal children were included in this study”, following by average mean ± Standard deviation, median age and sex-ratio of this children, before presented global prevalence of parasitic infections, frequency of co-infection and more…\nDiscussion? I think the made a mistake in the title section of the abstract. Please write “conclusion” instead of “discussion”.\nPage 3: Introduction Sentence 1: The two references cited are old and inappropriate. I recommend citing the WHO online document (Diarrhoeal disease: key facts, May 2, 2017) which is recent and, in my opinion, suitable for this affirmation.\nSentence 2: You say that diarrhea remains a major problem in terms of morbidity and mortality in children, which is true, but the references cited are not appropriate for this affirmation. I therefore recommend that you replace them with the following articles:\nEstimates of the global, regional, and national morbidity, mortality, and aetiologies of diarrhoea in 195 countries: a systematic analysis for the Global Burden of Disease Study 2016 (Christopher Troeger et al., 2018); Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000-17: analysis for the Global Burden of Disease Study 2017. Lancet. 2020 Jun 6;395(10239):1779-1801. doi: 10.1016/S0140-6736(20)30114-8. GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1736-1788. doi: 10.1016/S0140-6736(18)32203-7.\nSentence 3: You claim: “More than 1 billion episodes occur […] than 5 years in developing countries”. This assertion is out of date, because thanks to advances in vaccination (e.g., the extension of rotavirus vaccination) and treatment (e.g., ORS), the burden of diarrheal disease has fallen considerably. Studies show that, over the last three decades, children under 5 years of age have accounted for the majority of deaths from diarrhoeal diseases, with around 1.7 million children in this age group dying in 1990. Your figure of 2.5 million deaths among children under 5 in developing countries is incorrect. Today, interesting data on mortality linked to diarrheal diseases in children are shown by:\nWHO, title: Diarrheal diseases: highlights, posted online May 2, 2017.\n\nThis online document shows that there are around 1.7 billion cases of childhood diarrhea each year worldwide, and that diarrhea kills 525,000 children under the age of 5 each year).\nBernadeta Dadonaite, Hannah Ritchie and Max Roser (2018) - \"Diarrheal diseases\". Published online at OurWorldInData.org. Retrieved from: 'https://ourworldindata.org/diarrheal-diseases' [Online Resource].\nAccording to this article available online, diarrhea killed 500,667 children under 5 worldwide in 2019.\nAlternatively, you could say: “There are around 1.7 billion cases of childhood diarrhea each year, and diarrhea is estimated to have killed 500,667 children under the age of 5 worldwide in 2019”. (In this case, you'll need to cite the two online articles above).\nI recommend that you modify sentence 3 according to one of the three choices I've indicated above.\nSentence 7: There's an error in the reference numbering; instead of reference number 10, you've written reference number 15. Please correct this error.\nOverall, the introductory section needs to be revised, focusing on the most relevant references related to the topic and the most recent, preferably less than 5 years old, as I demonstrated above.\nMethods For greater clarity, please organize the following additional sections:\nEthical considerations ; Design, area and period of study Participants (inclusion and exclusion criteria), sample collection and storage Nucleic acid extraction (already present) PCR amplification and parasite detection (already present) Statistical analysis (this is currently missing entirely).\nData on the total number of samples collected, as well as frequencies of hospitalized diarrheic children can be presented in the \"results\" section (below) in a section entitled \"demographic data on the study population\".\nSection “PCR amplification and parasite detection”: In the last sentence, the authors state that \"Table 1 shows the sequences of the primers, probes and targeted genes, as well as the expected sizes\", which is partially true as the expected sizes are not shown in Table 1. Please make the necessary corrections.\nTable 1 also contains several references, both for organisms (reference number 5) and probes (reference numbers 16 and 19). I think this is a mistake! If not, please formulate appropriate sentences citing these references in the text before putting them in Table 1.\nResults There is some confusion between Cryptosporidium spp and Cryptosporidium parvum in this section. Cryptosporidium spp. refers to the genus Cryptosporidium, which includes over 30 species identified in mammals (C. parvum and C. hominis followed by C. mealegridis are the main species identified in humans), while C. parvum refers to a species of the genus Cryptoporidium, which is a so-called zoonotic species, unlike C. hominis, which is anthroponotic. I think you mean C. parvum, since according to the Verweij et al article first quoted in the methods section, the Cryptosporidium primers used were specific to C. parvum. Modifications therefore need to be made to this part of the work, in particular to the text and Tables 3, 4 and 5, as well as to the discussion.\nFor greater clarity, please organize the following additional sections:\nDemographic data Prevalence of parasitic infections (modify figure 1 into diagram) Parasitic mono- and co-infections (modify table 5) Distribution of mono- and co-infections by sex, age and seasonality.\nDiscussion Paragraph 5: the last quotation (reference number 13) does not correspond to the penultimate sentence (But our result differed [...] from the age of the group by ≤ 2 years;).\nOverall, the research results are not sufficiently valued. Limitations or weaknesses are not sufficiently highlighted.\nIs the work clearly and accurately presented and does it cite the current literature? No. Some of the bibliographical references cited are not appropriate to the assertion or argument put forward. In addition, there is an error in the numbering of the references cited by the authors.\nIs the study design appropriate and is the work technically sound? Partly. Although the work may have academic value, the study design is a little confusing, as some of the results on the demographic characteristics of the children included in the study are mixed with information on the study design. Inclusion and exclusion criteria for hospitalized children are not clearly presented. The study design needs to be properly reformulated.\nAre sufficient details of methods and analysis provided to allow replication by others? Partly.\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo. The statistical analyses carried out have not been set out in the \"Methods\" section, making interpretation of the results inappropriate. Furthermore, when percentages are mentioned, it is preferable to provide the figures used to calculate the prevalence or percentage, enabling the reader to interpret and evaluate the results more clearly.\nAre all the source data underlying the results available to ensure full reproducibility? Partly.\nAre the conclusions drawn adequately supported by the results? Partly.\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "10963",
"date": "22 Mar 2024",
"name": "Mosab Adam",
"role": "Author Response",
"response": "Thanks for these informative comments. I found it precise and increased the quality of our manuscript. We took all reviewer comments, made corrections throughout the paper, and updated this version. 1. rewrote the abstract section and updated it according to the reviewer's suggesting 2. we update the introduction section by rewriting the updated information, adding new updated references, and deleting the old ones 3. rewrote the method section, added the missing information, and updated carefully with the help of reviewers' comments 4. rewrote the result section, updated and classified it as the subtitle, added the statistical part, updated the tables and the diagram 5. update the discussion section and address the reviewer's comments"
},
{
"c_id": "11714",
"date": "20 Jun 2024",
"name": "Mosab Adam",
"role": "Author Response",
"response": "Thanks for your valuable comments I corrected that point you mentioned as I changed gender to sex, then rewrote the sentence in a clear way and corrected the sentence in the text that you commented on it"
}
]
}
] | 1
|
https://f1000research.com/articles/11-1401
|
https://f1000research.com/articles/13-1267/v1
|
23 Oct 24
|
{
"type": "Policy Brief",
"title": "Renewable energy: A way out for South Sudan’s electricity crisis",
"authors": [
"Aban Ayik",
"Nelson Ijumba",
"Nelson Ijumba"
],
"abstract": "South Sudan is one of the least electrified countries in the world, despite having abundant renewable energy resources that could be exploited to generate electricity. The country relies on imported diesel for electricity generation, besides having limited focus on renewable energy development. This policy brief sheds light on the potential of renewable energy as a solution to South Sudan’s ongoing electricity crisis. It examines the key factors hindering the development of renewable energy resources for electricity generation in the country. The brief also provides recommendations to the Government of South Sudan, policymakers, experts, and funding institutions on how to improve electricity access in the country. It is stressing on the importance of prioritising the development of diverse renewable energy resources, such as solar, wind, and small hydropower, as an immediate solution to the electricity access challenges in the country.",
"keywords": [
"Electricity access",
"renewable energy",
"policy recommendations",
"strategic plan",
"South Sudan."
],
"content": "Introduction\n\nIn South Sudan only 5.4% of the population have access to electricity.1 The country has no operational oil refineries and it depends on imported diesel for electricity generation. The current operational thermal power plants are mainly located in the capital city, Juba. In addition, there is no national electric grid to transmit the electricity generated in and around Juba to other parts of the country. The Government has been planning to improve the electricity access in South Sudan by building a national transmission network in addition to constructing a large hydropower plant.2 However, most of these plans have not succeeded, mainly due to financial constraints.\n\nA number of studies have shown that South Sudan has abundant renewable energy resources that can be exploited to generate electricity for almost the entire country. However, renewable electricity remains negligible in the power generation mix in South Sudan. Countries in the region such as Rwanda, Tanzania, Kenya, and Uganda are already improving their electricity access by using on-grid and off-grid renewable energy solutions such as solar, wind, and hydropower. So, what is delaying South Sudan from similarly unlocking its local renewable energy potential to improve its electricity access?\n\nThe aim of this policy brief is to examine the key factors delaying the development of renewable energy in South Sudan and to propose recommendations for improvement through exploitation of renewable energy resources.\n\n\nPolicy outcomes and implications\n\n\n\na) Available renewable energy capacity\n\nFigure 1(a-c) shows the solar, wind and small hydropower potentials of South Sudan. Solar energy is the most abundant renewable resource throughout the country. Many locations receive annual global irradiation above 5.0 kWh/m2, making it feasible for the development of large-scale solar power plants. Wind potential is generally low in the country, but there are areas where the annual average wind speed reaches 5.08 m/s at a height of 10 meters,3 and therefore small wind turbines could be developed there. There are about 82 potential small hydropower sites along the White Nile and Kaya rivers, in the southern parts of South Sudan, which can produce a total output power of 165.69 MW.4\n\nb) Factors limiting renewable energy uptake in South Sudan\n\nThe following were identified as contributing factors to the poor uptake of renewable energy in South Sudan:\n\ni. Limited focus on renewable energy resources in South Sudan’s Strategic and National Development Plans\n\nIn South Sudan’s Vision 2040, renewable energy resources are not prioritised. Vision 2040 only highlights hydropower development as a strategic priority, with no mention of other renewable energy resources. In the Revised National Development Strategy (R-NDS) 2021-2024,2 which is the current national development plan anticipated to guide South Sudan’s economic growth, it is stated that the country will invest in renewable energy, specifically hydropower. The Fula hydropower project was prioritised and allocated funding, and construction was scheduled to begin in 2022 and is expected to take 10 years to complete. However, work has not begun due to financial constraints.\n\nii. Reliance on imported electricity from neighbouring countries\n\nAuthorities in South Sudan have been focusing on importing electricity from neighbouring countries since 2011, although importing electricity is not a strategic priority in South Sudan’s national development plans. Electricity has been supplied to Renk, a county in the northern part of South Sudan, from Sudan since 2007 and continued after the country’s independence in 2011.5 However, there has been a surplus of electricity because it could not be transmitted to nearby counties or towns due to the absence of a transmission grid. Thus, as of 2022, Renk was using only 5% of the imported electricity.6 Additionally, since 2013, there have also been plans to import electricity from Ethiopia, which continue to this day.5,7 New plans include importing electricity from Uganda to provide power to towns at the border between Uganda and South Sudan.\n\nc) Implications\n\n• Lack of clear policy priorities: Without clear goals and policy priorities for the development of renewable energy resources outlined in South Sudan’s long-term and medium-term plans, authorities may not be able to allocate resources or create necessary regulations and incentives to encourage their development.\n\n• Unsustainability of electricity imports: Importing electricity from neighbouring countries may not be sustainable because electricity can be interrupted by different geopolitical factors.\n\n• Challenges with hydropower development: Although hydropower is a renewable energy resource, it faces significant environmental challenges, in addition to schedule and cost overruns.\n\n\nActionable recommendations\n\nThe following are actionable recommendations for the Government of South Sudan, policy makers, experts, and regional and international institutions that support development projects in the country:\n\ni. Prioritise the development of diverse renewable energy resources in future development plans for South Sudan\n\nSouth Sudan has diverse renewable energy resources that can be used to generate electricity. While some locations lack large hydropower potential, they have abundant solar resources, along with potential for small wind turbines and small and mini hydropower development. Biomass and geothermal resources are also anticipated in some locations in the country. Therefore, policy makers should prioritise the exploration, assessment and development of other renewable energy resources beyond hydropower in the country’s future development plans.\n\nii. Prioritise developing a phased plan to build a national transmission and distribution network\n\nBuilding an electricity transmission network across a country, though costly, is essential for enabling increased access to electrical energy. Therefore, policy makers and experts should develop a comprehensive network construction plan that can be implemented in manageable phases. Regional and international financial institutions should prioritise funding such a project through grants and loans.\n\niii. Invest in mini-grids and off-grid solar energy projects\n\nDue to costs and physical terrain considerations, the national transmission grid would not cover the whole country. Therefore, there will still be a need for investing in mini-grid and off-grid systems, particularly in rural and remote areas, where the majority of the population lives. Since solar energy potential is high throughout South Sudan, solar energy-based mini-grids and off-grid systems can offer viable solutions to improve electricity access in these locations.\n\niv. Incentivising investors and private energy property developers\n\nTo attract investors and private companies it is essential to make investments in renewable energy projects attractive. This is possible by providing grants and tax incentives, as well as simplifying regulations for investing in such projects.\n\nv. Conduct thorough techno-economic studies on importing electricity to South Sudan\n\nIt is imperative to conduct in-depth techno-economic studies to assess and compare the feasibility of importing electricity from neighbouring countries versus developing local renewable energy resources. Regional integration and cooperation through trade with neighbouring countries are beneficial and highly encouraged. Therefore, it is vital to thoroughly evaluate the technical feasibility, economic viability, and potential impacts and risks associated with such projects before their commencement to avoid future conflicts.\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nReferences\n\nIEA, IRENA, UNSD, World Bank, WHO: Tracking SDG 7: The Energy Progress Tracking Report.2024. Reference Source\n\nGRSS and UNDP: Revised National Development Strategy 2021–2024: Consolidate peace and stabilize the economy. Juba: 2021.\n\nAyik A, Ijumba N, Kabiri C, et al.: Preliminary wind resource assessment in South Sudan using reanalysis data and statistical methods. Renew. Sust. Energ. Rev. Mar. 2021; 138: 110621. Publisher Full Text\n\nAyik A, Ijumba N, Kabiri C, et al.: Preliminary assessment of small hydropower potential using the Soil and Water Assessment Tool model: A case study of Central Equatoria State, South Sudan. Energy Rep. Dec. 2023; 9: 2229–2246. Publisher Full Text\n\nThe World Bank: Republic of South Sudan: Electricity Sector Strategy Note for South Sudan.2013.\n\nEye Radio: Renk assures willing investors of stable power supply.2022. (accessed Jul. 02, 2024). Reference Source\n\nThe East African: South Sudan signs up for Ethiopia Dam power.2022. (accessed Jul. 02, 2024). Reference Source"
}
|
[
{
"id": "334853",
"date": "08 Nov 2024",
"name": "Barnaby Joseph Dye",
"expertise": [
"Reviewer Expertise Development studies",
"Africa Studies",
"Political Economy",
"The politics of infrastructure and the electricity Sector in Africa"
],
"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 construction of the problem – detail of what is possible and the negative implications of the present context are well made. The text is clearly articulated and the maps useful\nThe word ‘Delay’ – assumes that South Sudan’s government wants to deploy renewables – or that it is inevitable\nAre there interest groups set against? The authors later mention that the government’s 2040 vision doesn’t support conventional renewables – only large hydropower\n\nThe focus on large hydropower is rooted in longstanding ideas of development and electricity found across Africa, but also in Sudan (Which I presume South Sudan partly inherited?) and neighbouring Ethiopia and Egypt\nThe authors are right to point to environmental problems and cost overruns and construction delays\n\nThis seems to me a political problem therefore – simplistically a lack of ‘will’ – but which probably has deeper roots\nI presume there are many invested in the oil economy and in importing refined oil from abroad? Are there also strong political interests in generators? In other countries like Nigeria these are key explainers of renewable non-development/lack of grid extension etc At some stage this needs to be mentioned as a constraint or possibility for the future, or that understanding the political economy context would be a recommendation for investors/donors attempting to build new electricity infrastructure\n\nI am surprised that conflict and civil war is not mentioned once when it is so fundamental to the why infrastructure is difficult to achieve, constrained resources, lack of investment and the government’s ability to act. This is surely a key context even if beyond the scope of the recommendations here\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? Yes\n\nAre the recommendations made clear, balanced, and justified on the basis of the presented arguments? Partly",
"responses": []
},
{
"id": "347920",
"date": "04 Feb 2025",
"name": "Taco Niet",
"expertise": [
"Reviewer Expertise Energy Systems",
"Sustainable Energy",
"Energy Systems Modelling",
"Renewable Energy",
"Energy Storage"
],
"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: The article presents policy suggestions for South Sudan to expand electricity access. The article argues that large hydro, imports and a dependence on oil are currently the focus in SS but that this should be revised to encourage deploying renewables across the country instead. It also notes challenges building out the electricity grid due to financial constraints.\nThere are a few issues that I think should be addressed:\nThe context in SS is not well developed. There was recent civil war that ended only a few years ago, and there is ongoing ethnic violence. This makes it much more challenging to address energy issues and access capital for development of any sort.\nThere is an implicit assumption that RE deployment will automatically increase electricity access. This hasn't been established in the article and is not necessarily the case. More imports and large power plants can also contribute to access.\nYou discuss that importing electricity is not sustainable but also recommend continuing regional cooperation. Reducing imports will likely reduce electricity access so hard to justify not continuing imports. Also Recommendation v statements are counter to each other - encourage regional integration but also not. Which is it?\nIn Factors ii you say imported electricity is not used. This is non-sensical - the grid doesn't work that way. If electricity is imported it is used. Clarify what you mean by this statement.\nCurrent electricity access (2022) is 8.4% https://data.worldbank.org/indicator/EG.ELC.ACCS.ZS?locations=SS. But also 5.4% per IRENA's report. Maybe give a range or discuss why the number might vary. This is likely indicative of the issues in SS - lack of infrastructure makes it challenging to accurately assess such numbers. Worth a mention.\nRecommendation i - might also discuss the fact that RE development requires smaller quanta of capital compared to large projects so can be easier to get going.\nRecommendation iv - Private equity does not show up in the policy issues so why is this a recommendation? Where is the current policy issue with private equity? This again speaks to the lack of context for SS as a country.\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? Yes\n\nAre the recommendations made clear, balanced, and justified on the basis of the presented arguments? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1267
|
https://f1000research.com/articles/13-540/v1
|
28 May 24
|
{
"type": "Research Article",
"title": "Length-weight relationship and condition factor of Nile tilapia (Oreochromis niloticus) fed diets supplemented with guava and star gooseberry leaf extract",
"authors": [
"Manoj Tukaram Kamble",
"Krishna Rugmini Salin",
"Balasaheb Ramdas Chavan",
"Seema Vijay Medhe",
"Kim D. Thompson",
"Nopadon Pirarat",
"Manoj Tukaram Kamble",
"Krishna Rugmini Salin",
"Balasaheb Ramdas Chavan",
"Seema Vijay Medhe",
"Kim D. Thompson"
],
"abstract": "Background Nile tilapia (Oreochromis niloticus) is predominant cultured species in aquaculture. However, there is a scarcity of literature regarding relationship between guava and star gooseberry leaf extract and the condition factor. Thus, the present study aims to investigate the effect of guava and star gooseberry leaf extract-supplemented diets on the specific growth rate, length-weight relationship, and condition factor of Nile tilapia.\n\nMethods Six hundred and thirty Nile tilapia (8.7±0.4 g) were randomly distributed among twenty-one tanks (30 fish per tank) within a recirculation system. Over a 60-day period, the fish were fed diets supplemented with 5g/Kg and 10g/Kg of guava leaf extract (GLE-5, GLE-10), star gooseberry leaf extract (SGLE-5, SGLE-10), and a mixture of both (MxLE-5, MXLE-10). Subsequently, specific growth rate, length-weight relationship, and condition factor were determined.\n\nResults After 60 days, the specific growth rate was significantly higher in all the GLE, SGLE, and MxLE groups compared to the control group. The final lengths and weights differed significantly both in the control group and all the GLE, SGLE, and MxLE groups. The analysis of the regression equation indicated a positive correlation (r = 0.970, 0.977, 0.976, 0.974, 0.974, 0.974, and 0.969) between the length and weight of Nile tilapia in the control group and in all the GLE, SGLE, and MxLE groups. The regression exponent \"b\" values in all the GLE, SGLE, and MxLE groups were >3, indicating a positive allometric growth pattern in Nile tilapia compared to the control (b=2.866), which exhibited a negative allometry. The final condition factor values did not differ significantly in either the control group or any of the plant extract groups.\n\nConclusions Nile tilapia exhibited positive allometric growth patterns and maintained good health when fed with GLE, SGLE, and MxLE groups. Therefore, these plant extracts demonstrate suitability for commercial Nile tilapia production.",
"keywords": [
"Nile tilapia",
"length-weight relationship",
"condition factor",
"specific growth rate",
"guava",
"star gooseberry"
],
"content": "Introduction\n\nNile tilapia (Oreochromis niloticus) is recognized as an important species in aquaculture within tropical and subtropical regions, owing to its faster growth, heightened productivity, and notable resistance to diseases.1–4 In 2020, the global production of Nile tilapia nearly reached 4.9 million metric tons (Mmt), and the continuous growth is attributed to the robust worldwide demand.5 Furthermore, technological advancements with high stocking densities play a significant role in the occurrence of disease outbreaks, resulting in substantial economic losses and impeding the sustainable progression of tilapia culture globally.6\n\nThe incorporation of plant extracts into aquafeed is significant in finfish aquaculture7 because the indiscriminate use of antibiotics has led to the development of drug-resistant bacteria.8,9 Plant extracts can serve as cost-effective and environmentally sustainable prophylactic or antimicrobial agents. Guava (Psidium guajava) leaf (GLE) are rich in various phenolic and flavonoid compounds10 and possess antimicrobial,11 antiviral,12 and antioxidant13 activities. GLE have been employed as supplements in fish feed to boost the growth, immune response, and protection against diseases for various fish species.14–20 Star gooseberry (Phyllanthus acidus) leaf (SGLE) contain flavonoids, kaempferol, hypogallic acid, caffeic acid, and phenolic compounds.21,22 SGLE exhibited antioxidant, anti-inflammatory and antimicrobial activities.23,24 It is also employed as a dietary supplement to augment the immune response of fish9,25 and chickens.26\n\nThe length-weight relationship (LWR) plays an essential role in estimating the biomass of diverse fish populations.27 Additionally, LWR is valuable for assessing fish condition and growth patterns.28 The condition factor (CF) contributes to comprehending the development and adaptability of fish.29 A heightened condition factor indicates the robust health and positive growth of the fish.30 Hence, the condition factor can be employed to assess the feeding activity of a species, indicating its effective utilization of available feeding sources.27 Previous studies have investigated the length-weight relationship and feeding habits of tilapia.27,30–33 Unfortunately, there is a scarcity of literature regarding relationship between guava and star gooseberry leaf extract and the condition factor. Thus, the present study aims to investigate the effect of guava and star gooseberry leaf extract-supplemented diets on the specific growth rate, length-weight relationship, and condition factor of Nile tilapia.\n\n\nMethods\n\nThe analytical grade chemicals utilized for the determination of Ammonia, Nitrite, and Nitrate from the experimental tanks included Sodium Hypochlorite 10% (Commercial, U&V Holding (Thailand) CO., LTD), Hydrochloric acid, 37% (Fisher Scientific UK), Sodium hydroxide (Pine Chemical, Finland), Phenol, 99+% (Fisher Scientific UK), Sulfanilamide (Acros Organics Bvba, Belgium), N-(1-Naphthyl) ethylenediamine dihydrochloride (Alfa Aesar, USA), Cadmium granular (ALDRICH Chemical, USA), Manganese (II) Sulphate H2O, Ammonium Chloride, Sodium Nitrite, Copper (II) sulfate, and Ethylenediamine Tetra Acetic acid (Daejung Chemicals and Metals, South Korea), as well as Sodium Tetraborate and Potassium Nitrate (KEMAUS, Australia) (Underlying Data).34\n\nThe guava (P. guajava) and star gooseberry (P. acidus) leaf powder were received from All-Season Herbs Pvt. Ltd., Bangalore, India and the aqueous extract was prepared.35 Briefly, distilled water (100 mL) was mixed with leaf powder (10 g) and homogenized using an orbital shaker (Hsiangtai D500) at 100 rpm for 20 h at room temperature (RT). The resultant mixture underwent centrifugation at 8,000 rpm for 15 min at RT. A rotavapor (BÜCHI R-200/205) at 35 °C used to evaporate the supernatant and continue drying for 48 h in a hot air oven at 50 °C. The dried samples obtained were placed in bottles and kept refrigerated at 4°C until further use.\n\nThis study was conducted under the project entitled ‘Application of Phytobiotic Supplementation to Improve Disease Resistance of Nile Tilapia (Oreochromis niloticus)' and funded by the Social Justice and Special Assistance Department, Government of Maharashtra, India, and Second Century Fund (C2F) Postdoctoral Fellowship, Chulalongkorn University, Bangkok, Thailand. This study was carried out in strict accordance with the recommendations of the Asian Institute of Technology (AIT), Thailand, and the protocol was approved by the Local Ethical Committee for Experiments on Animals of the AIT, Thailand (Project Number: AIT-AQ-18-01, May 2018–April 2019; April 29, 2018). Additionally, according to Thailand Legislation, the Nile tilapia were not categorized as a protected species. The research was carried out at the Laboratory of the Aquaculture and Aquatic Resources Management (AARM, Asian Institute of Technology (AIT), Thailand, over 60 days from February to March, 2019. This study is reported in line with the ARRIVE guidelines. A total of 630 fish were used in the experiment, with 90 fish allocated to each treatment. Each treatment comprised 30 fish per replicate, totaling three replicates. Prior to sampling, the fish underwent a 12-hour fasting period to empty their digestive tracts. In this study, to reduce stress on the experimental animals, the animals housed in the containers were gently anesthetized using 1 mL of clove oil per 10 L of water for a period of 2–3 min, after which their weights were measured. Following this, the fish were returned to their designated glass tanks according to their treatment and replication groups.\n\nNile tilapia monosex fingerlings (8.7 ± 0.4 g and 8.0 ± 1.0 cm) were obtained from a GMP Certified fish farm, Ayutthaya Province, Thailand. The research was conducted at the laboratory of Aquaculture and Aquatic Resources Management (AARM), Asian Institute of Technology (AIT), Thailand. For a period of 15 days, the fish were acclimatized in three fiberglass tanks (500 L) before the commencement of the experiment. Fish were fed pelleted feed twice daily at 4% of their body weight. Following the acclimatization period, the fish were randomly distributed among twenty-one 150-L glass tanks (30 fish per tank), all integrated into a recirculation system.\n\nPlant extracts (10 mg), dissolved in 1 mL distilled water, were mixed with commercial feed ((Charoen Pokphand (CP)-7710), and spaghetti-like strands were prepared using a mincer (MITSUYAMA YC80B-4). Pellets approximately 5 mm in length were formed and dried for 24 h at 50 °C in a hot air oven. The dried pellets were then stored at 4 °C until the end of the experiment. The proximate composition of the commercial diet, including moisture, ash, crude lipid, and crude protein, was 7.6%, 8.2%, 6.5%, and 30.5%, respectively.\n\nIn this study, a completely randomized design was employed, comprising seven experimental treatments: 5g/kg and 10g/kg of guava leaf extract (GLE-5, GLE-10), star gooseberry leaf extract (SGLE-5, SGLE-10), and a mixture of both (MxLE-5, MXLE-10). The mixed diets (MxLE) were prepared with an equal proportion (1:1) of GLE and SGLE extracts. The control group, on the other hand, was fed a diet without plant extract supplementation. Fish were fed twice daily at 4% of their body weight. Prior to sampling, the fish underwent a 12-hour fasting period to empty their digestive tracts. In this study, to reduce stress on the experimental animals, the animals housed in the containers were gently anesthetized using 1 mL of clove oil per 10 L of water for a period of 2–3 min, after which their weights were measured. Following this, the fish were returned to their designated glass tanks according to their treatment and replication groups. The specific growth rate, length-weight relationship, and condition factor were determined after 60 days of feeding.\n\nDuring the experiment, a Eutech Cyberscan PC300 multi-parameter apparatus was employed to measure daily water quality parameters, including temperature, pH, and dissolved oxygen (DO). The weekly concentrations of ammonia-nitrogen (NH3-N) were assessed using Phenate or indophenol method,36 nitrite-nitrogen (NO2-N) concentrations were quantified through direct spectrophotometric assay,36 and nitrate-nitrogen (NO3-N) levels were determined employing cadmium reduction method.36\n\nThe specific growth rate37 was evaluated after 60 days of feeding trials using the following equation\n\nLength-weight relationship (LWR)38 between the total length and body weight was estimated using the following formula\n\nWhere W is body weight of fish (g), L is the total length (cm), a is the exponent denotes the rate of weight change with length (constant), and b is the slope representing the weight of one unit length. These values are estimated through the linear regression equation, which is transformed by applying the natural logarithm (Log) to both sides.\n\nWhere b = 3, growth pattern is isometric. However, when b is greater or less than 3, an allometric pattern emerges. This allometric pattern can be positive, indicating increase in length relative to body thickness, or negative, signifying an increase in length relative to body thinness.28\n\nThe health condition of the tilapia was assessed by evaluating relative condition factor (Kn) in all the treatments.\n\nThe results were presented as means ± SE, and statistical analysis was conducted using IBM SPSS Statistics software (SPSS, Inc., Version 29). The homogeneity of data was determined using Levine’s test. The impact of plant extract treatments on specific growth rate was assessed through one-way analysis of variance (ANOVA), followed by Tukey post-hoc tests for multiple comparisons. An independent t-test was used to determine the significant difference between the initial and final length and weight of Nile tilapia with plant extract treatments. Linear regression analysis was employed to evaluate the length-weight relationship. A significance level of p < 0.05 was considered for statistical significance.\n\n\nResults\n\nWater quality parameters such as Temperature, pH, DO, NH3N, NO2N, and NO3N, did not show significant difference among the plant extract treatments and control during the experiment (Table 1). In all treatments, the average values for temperature, pH, DO, NH3N, NO2N, and NO3N were 29.6 °C, 7.47, 5.49 mg/L, 0.15 mg/L, 0.13 mg/L, and 0.23 mg/L, respectively. Raw data are available as underlying data (Tables 1-6).34\n\nThe survival rate was higher than 95% in all treatments. The specific growth rate was significantly higher in all plant extract treatments compared to the control group. GLE-10 exhibited a higher SGR, while MxLE-10 showed a lower SGR in the plant extract treatments (Figure 1). Raw data are available as underlying data (Table 7).34\n\nResults with the means of three replicates ± SE; Different superscripts in the bar indicate significant difference (p < 0.05).\n\nThe lengths were significantly different at the end of the experimental period in the control (t(148)=-30.327, p=0.01), GLE-5 (t(148)=-37.193, p=0.01), GLE-10 (t(148)=-32.297, p=0.01), SGLE-5 (t(148)=-37.552, p=0.01), SGLE-10 (t(148)=-28.491, p=0.01), MxLE-5 (t(148)=-31.824, p=0.01), and MxLE-10 (t(148)=-38.139, p=0.01) groups (Table 2). Additionally, the weights were significantly different at the end of the experimental period in the control (t(148)=-31.206, p=0.01), GLE-5 (t(148)=-38.611, p=0.01), GLE-10 (t(148)=-32.694, p=0.01), SGLE-5 (t(148)=-37.627, p=0.01), SGLE-10 (t(148)=-30.032, p=0.01), MxLE-5 (t(148)=-32.800, p=0.01), and MxLE-10 (t(148)=-38.197, p=0.01) groups.\n\nThe analysis of the regression equation indicated a positive correlation (r = 0.970, 0.977, 0.976, 0.974, 0.974, 0.974, and 0.969) between the length and weight of Nile tilapia fed control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, MxLE-10 diets, respectively.\n\nThe regression exponent of “b” values in GLE-5 (b=3.023, t(73)=39.216, p=0.01), GLE-10 (b=3.101, t(73)=38.515, p=0.01), SGLE-5 (b=3.067, t(73)=36.981, p=0.01), SGLE-10 (b=3.003, t(73)=36.451, p=0.01), MxLE-5 (b=3.135, t(73)=36.816, p=0.01), and MxLE-10 (b=3.036, t(73)=33.390, p=0.01) were >3, indicating a positive allometric growth pattern in Nile tilapia compared to the control (b=2.866, t(73)=33.881, p=0.01), which exhibited negative allometry. The length-weight correlation regression graphs for the control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, MxLE-10 diets are depicted in Figure 2. Raw data are available as underlying data (Tables 8-14).34\n\nThe condition factors were not significantly different at the end of the experimental period in the control (t(148)=-0.599, p=0.275), GLE-5 (t(148)=-0.199, p=0.421), GLE-10 (t(148)=0.299, p=0.383), SGLE-5 (t(148)=0.818, p=0.207), SGLE-10 (t(148)=0.173, p=0.431), MxLE-5 (t(148)=0.371, p=0.356), and MxLE-10 (t(148)=-0.100, p=0.460) groups (Table 2). Additionally, the minimum and the maximum values of condition factor for control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups were 0.865-1.177, 0.886-1.178, 0.824-1.097, 0.840-1.282, 0.817-1.162, 0.857-1.136, and 0.822-1.162, respectively. Raw data are available as underlying data (Tables 8-14).34\n\n\nDiscussion\n\nAquafeed supplementation with herbal or plant extracts has proven to be an effective means of enhancing the growth performance, feed utilization, and immune response in farmed fish species.40,41 The supplementation of natural bioactive rich-plant extracts may boost natural immunity and improve disease resistance,40 resulting in higher production and profitability in the aqua industry. The length-weight relationship is used to predict the weight of fish in proportion to their length over a certain period.38 Therefore, the present study investigated the effects of plant extract-supplemented diets on the length-weight relationship and condition factor of Nile tilapia.\n\nThe water quality parameters in all treatments were within the acceptable range, consistent with the findings of previous studies on spotted snakehead (Channa punctata) under various feeding regimes involving agro-industrial by-products,42 and on silver barb (Barbonymus gonionotus) fingerlings fed with dietary blanched moringa leaf meal.43 The specific growth rate showed a significant increase in all plant extract treatments. Similarly, the specific growth rate of spotted snakehead (C. punctata) and silver barb (B. gonionotus) was considerably improved under various feeding regimes involving agro-industrial by-products42 and dietary blanched moringa leaf meal.43\n\nAqua farmers and consumers prefer fish with isometric growth or body structure.27,44 Furthermore, the length-weight relationship provides insights into the growth and health of a fish species.45,46 In the present study, plant extract-supplemented diets observed significant correlation between length and weight of Nile tilapia. Our results are corroborated with previous study involving different maltose levels fed to Nile tilapia (O. niloticus).27 Importantly, Nile tilapia fed diets supplemented with GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups exhibited positive allometric growth pattern compared to the control. Similarly, silver barb (B. gonionotus) and zebrafish (Danio rerio) fed with dietary blanched moringa leaf meal43 and plant-protein based diets47 found positive allometric growth. On the contrary, gold fish (Carassius auratus) fed with different concentrations of carrot48 and gurami sago (Osphronemus goramy) stocked in concrete ponds, floating net cages, and earthen freshwater ponds,49 found negative allometric growth.\n\nIn the present study, plant extracts diets revealed a significant improvement in specific growth rate and positive allometric growth patterns of Nile tilapia. This can be ascribed to the presence of bioactive compounds in GLE and SGLE, including gallic acid, p-coumaric acid, quercetin, and kaempferol. These compounds have been demonstrated to enhance the growth of various fish species, including common carp Cyprinus carpio,50 snakehead fish Channa argus,51 grass carp Ctenopharyngodon idellus,52 as well as certain animals.53,54 Further research should be conducted in pond or cage culture systems to substantiate the positive allometric growth patterns exhibited by Nile tilapia when fed diets supplemented with GLE and SGLE.\n\nThe mean Kn values for both the plant extract diets and control were higher than one, indicating that the Nile tilapias were in good health condition during the experimental period. Similarly, condition factor values were more than one when Sargassum meal fed to Nile tilapia O. niloticus,31 Mansoa alliacea hydroalcoholic extracts fed to pirarucu Arapaima gigas,55 different maltose levels fed to Nile tilapia O. niloticus.27\n\n\nConclusion\n\nThe specific growth rate was significantly higher in GLE, SGLE, and MxLE groups compared to the control group. The analysis of the regression equation indicated a positive correlation between the length and weight of Nile tilapia in the control group and the GLE, SGLE, and MxLE groups. Furthermore, the GLE, SGLE, and MxLE groups exhibited a positive allometric growth pattern in Nile tilapia compared to the control. The final condition factor values did not differ significantly between the control group and any of the GLE, SGLE, and MxLE groups. Consequently, these plant extracts demonstrate suitability for commercial Nile tilapia production.",
"appendix": "Data availability\n\nzenodo: Length-weight relationship and condition factor of Nile tilapia (Oreochromis niloticus) fed diets supplemented with guava and star gooseberry leaf extract. https://doi.org/10.5281/zenodo.11174309. 34\n\nThis project contains the following underlying data:\n\n- Table 1: Weekly average temperature (°C) of the control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups.\n\n- Table 2: Weekly average pH of the control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups.\n\n- Table 3: Weekly average DO (mg/L) of the control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups.\n\n- Table 4: Weekly average NH3N (mg/L) of the control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups.\n\n- Table 5: Weekly average NO2N (mg/L) of the control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups.\n\n- Table 6: Weekly average NO3N (mg/L) of the control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 groups.\n\n- Table 7: Specific growth rate of Nile tilapia (N=75) fed diets supplemented with control, GLE-5, GLE-10, SGLE-5, SGLE-10, MxLE-5, and MxLE-10 for 60 days.\n\n- Table 8: Initial and final length (cm), weight (g), and condition factor of Nile tilapia (N=75) fed diet supplemented with control for 60 days.\n\n- Table 9: Initial and final length (cm), weight (g), condition factor of Nile tilapia (N=75) fed diet supplemented with GLE-5 for 60 days.\n\n- Table 10: Initial and final length (cm), weight (g), and condition factor of Nile tilapia (N=75) fed diet supplemented with GLE-10 for 60 days.\n\n- Table 11: Initial and final length (cm), weight (g), and condition factor of Nile tilapia (N=75) fed diet supplemented with SGLE-5 for 60 days.\n\n- Table 12: Initial and final length (cm), weight (g), and condition factor of Nile tilapia (N=75) fed diet supplemented with SGLE-10 for 60 days.\n\n- Table 13: Initial and final length (cm), weight (g), and condition factor of Nile tilapia (N=75) fed diet supplemented with MxLE-5 for 60 days.\n\n- Table 14: Initial and final length (cm), weight (g), and condition factor of Nile tilapia (N=75) fed diet supplemented with MxLE-10 for 60 days.\n\n- Table 15: Summary of the chemicals and reagents used in the experiment.\n\n- Authors checklist Manuscript No. 145369 (completed ARRIVE 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\nAtaguba GA, Kamble MT, Salin KR: Food industry by-products as protein replacement in aquaculture diets of tilapia and catfishs. 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Publisher Full Text\n\nCai L, Li Y, Wei Z, et al.: Effects of dietary gallic acid on growth performance, diarrhea incidence, intestinal morphology, plasma antioxidant indices, and immune response in weaned piglets. Anim. Feed Sci. Technol. 2020; 261: 114391. Publisher Full Text\n\nSamuel K, Wang J, Yue H, et al.: Effects of dietary gallic acid supplementation on performance, antioxidant status, and jejunum intestinal morphology in broiler chicks. Poult. Sci. 2017; 96(8): 2768–2775. PubMed Abstract | Publisher Full Text\n\nDias MKR, Yoshioka ETO, Rodriguez AFR, et al.: Mansoa alliacea extract improves the growth performance and innate immune response of Arapaima gigas challenged with Aeromonas hydrophila and handling stress. Acta Amaz. 2023; 53: 24–31. Publisher Full Text"
}
|
[
{
"id": "303303",
"date": "07 Aug 2024",
"name": "Dr.Sheikh Muhammad Azam",
"expertise": [
"Reviewer Expertise fisheries",
"wildlife"
],
"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\nWork will attract the scientist in the field. The results will be helpful for farmers and aquaculturists.\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\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12663",
"date": "23 Oct 2024",
"name": "nopadon pirarat",
"role": "Author Response",
"response": "Comment 1: Work will attract the scientist in the field. The results will be helpful for farmers and aquaculturists. Response: Thank you for taking the time to review our manuscript. We appreciate your positive feedback and are glad to hear that you believe our work will engage scientists in the field. We aim to provide valuable insights that will benefit both farmers and aquaculturists, contributing to more sustainable practices in aquaculture. Your encouragement reinforces the importance of our research, and we look forward to sharing our findings with the broader community."
}
]
},
{
"id": "320437",
"date": "06 Sep 2024",
"name": "Agumassie Tesfahun",
"expertise": [
"Reviewer Expertise Assistant Professor in Fisheries and Aquatic 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\nI advice the authors to include correlation matrix or principal component analysis (PCA) regarding the water quality parameter and fish biometric relationships (length and weight). To this end, please refer other published works in the same title. The paper is sound, however, it should be more sound if the authors include more statistical analysis such as correlation matrix or principal component analysis (PCA) to know the relationship between environmental variables and fish biometric data. Except for this issue, the paper is well presented and innovative for the scientific community. Capture fishery is now declining due to human induced impacts on the water bodies. Aquaculture is the alternative option to feed this fast-growing population. Therefore, this work is very important for the fish farmers and the community as well for food security.\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": "12664",
"date": "23 Oct 2024",
"name": "nopadon pirarat",
"role": "Author Response",
"response": "Comment 1: I advice the authors to include correlation matrix or principal component analysis (PCA) regarding the water quality parameter and fish biometric relationships (length and weight). To this end, please refer other published works in the same title. The paper is sound, however, it should be more sound if the authors include more statistical analysis such as correlation matrix or principal component analysis (PCA) to know the relationship between environmental variables and fish biometric data. Except for this issue, the paper is well presented and innovative for the scientific community. Capture fishery is now declining due to human induced impacts on the water bodies. Aquaculture is the alternative option to feed this fast-growing population. Therefore, this work is very important for the fish farmers and the community as well for food security. Response: Thank you for your valuable feedback and appreciation of our work. We have incorporated a correlation matrix in the revised manuscript to analyze the relationships between water quality parameters and fish biometric data, specifically length and weight. This addition strengthens our analysis and aligns with your suggestion for more robust statistical evaluation. Your point regarding the declining capture fishery due to human-induced impacts is well taken. As aquaculture emerges as a vital alternative for sustaining the growing global population, our research aims to provide essential insights for fish farmers and contribute to food security efforts within communities. We appreciate your recognition of the significance of this work and look forward to any further suggestions you may have. In the revised manuscript Correlation matrix for water quality and fish biometric parameters The results of Pearson’s correlation analysis are presented in Table 3. A moderate positive correlation was observed between fish length and both ammonia (r = 0.403) and nitrite (r = 0.489), with the nitrite correlation being statistically significant at the 0.05 level (Table 3). This finding suggests that as fish increase in length, there may be a corresponding rise in ammonia and nitrite levels, potentially due to metabolic byproducts. Similarly, fish weight exhibited a positive correlation with ammonia (r = 0.470) and nitrite (r = 0.489), with the latter correlation also significant at the 0.05 level. These results indicate that fish biomass may contribute to the elevation of these water quality parameters. Furthermore, a significant negative correlation (r = -0.684) was identified between temperature and dissolved oxygen at the 0.01 level, indicating that higher temperatures are associated with reduced dissolved oxygen levels. This phenomenon is well-documented, as warmer water typically holds less oxygen. Additionally, temperature demonstrated a moderate negative correlation with pH (r = -0.563), which was also significant at the 0.01 level. Elevated temperatures may influence the ionization of water, leading to decreased pH levels. A strong positive correlation (r = 0.887) was observed between dissolved oxygen and pH, significant at the 0.01 level. Higher dissolved oxygen levels are often associated with elevated pH in aquatic systems, likely due to increased photosynthetic activity. Discussion The strong correlations between fish length, weight, and specific water quality parameters, particularly ammonia and nitrite, suggest a potential interplay between fish growth and water quality dynamics. As fish grow, their metabolic waste production, including ammonia, increases, which can accumulate in the environment if not adequately managed. This accumulation of ammonia and nitrite can adversely affect water quality and fish health, ultimately impacting growth rates and overall well-being. Several studies support these observations. Elevated ammonia concentrations are known to impair fish growth by disrupting metabolic processes and diminishing feeding efficiency. For instance, in the rockfish Sebastes schlegelii, exposure to high ammonia concentrations resulted in reduced growth performance. 56 Similarly, increased nitrite levels have been associated with oxidative stress and compromised respiratory function in fish, which can further inhibit growth. 57 In aquaculture systems, higher fish densities or insufficient water treatment often exacerbate the accumulation of ammonia and nitrite. Such conditions have been shown to decrease feed consumption and utilization efficiency, as demonstrated in studies examining the effects of stocking density on water quality and fish performance. 57, 58 These correlations underscore the necessity for meticulous management of water quality parameters in aquaculture to ensure optimal growth and health outcomes for fish populations. References 56) Shin KW, Kim SH, Kim JH, Hwang SD, Kang JC: Toxic effects of ammonia exposure on growth performance, hematological parameters, and plasma components in rockfish, Sebastes schlegelii, during thermal stress. Fish Aquat Sci. 2016;19:1–8. 10.1186/s41240-016-0044-6. 57) Al-Harbi AH, Siddiqui AQ: Effects of tilapia stocking densities on fish growth and water quality in tanks. Asian Fish Sci. 2000;13(4):391–396. 10.33997/j.afs.2000.13.4.011. 58) Sanders E, Farmer SC: Aquatic models: Water quality and stability and other environmental factors. ILAR J. 2019;60(2):141–149. 10.1093/ilar/ilaa008."
}
]
}
] | 1
|
https://f1000research.com/articles/13-540
|
https://f1000research.com/articles/13-639/v1
|
17 Jun 24
|
{
"type": "Research Article",
"title": "Kadukkai maathirai (Indian herbal drug) prevents hepatocellular cancer progression by enhancing GSTM1 expression and modulating β catenin transcription: in-silico and in-vivo study",
"authors": [
"Manjunath Shetty",
"Smita Shenoy",
"Arul Amuthan",
"Vasudha Devi",
"Nitesh Kumar",
"Amruth Kiran",
"Ganesh Shenoy",
"Diya Rajasekhar Chinta",
"Shama Prasada K",
"Akshatha Shetty",
"Mohandas Rao K G",
"Manjunath Shetty",
"Arul Amuthan",
"Vasudha Devi",
"Nitesh Kumar",
"Amruth Kiran",
"Ganesh Shenoy",
"Diya Rajasekhar Chinta",
"Shama Prasada K",
"Akshatha Shetty",
"Mohandas Rao K G"
],
"abstract": "Background Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor clinical outcomes. Hence cost-effective drugs with fewer side effects as a standard supportive therapy might yield substantial advantages in efficacy and safety. Kadukkai maathirai (KM) is being used as a supplement in hepatocellular carcinoma. We evaluated whether KM has any preventive action on cancer progression in diethyl nitrosamine (DEN) - induced HCC in rats.\n\nMethods DEN was injected to produce HCC in rats, which was confirmed after 16 weeks. All the rats were orally administered KM for 4 weeks. Hepatoprotective potential (serum AST, ALT, ALP, Bilirubin) and anticancer efficacy (body weight, nodule count, tumor progression by histopathology, expression of GSTM1 by Liquid chromatography-mass spectrometry (LC-MS), and In-silico analysis of phytoconstituents against β catenin and LRP analysis were evaluated.\n\nResults KM prevented cancer progression against DEN-induced HCC by an increase in GSTM1, a phase II detoxifying enzyme. It significantly reversed altered nodule count, relative liver weight, body weight, and histopathological features of HCC. In silico analysis of phytoconstituents of KM showed that they modulate the intracellular transcription process by inhibiting the armadillo repeat region of β catenin.\n\nConclusions Our results elucidate the potential of KM as a supplement in HCC by reducing nodule count, protecting the liver from further damage, GSTM1 expression, and inhibiting armadillo repeat region of β catenin.",
"keywords": [
"β catenin",
"Glutathione-S transferase mu 1",
"Siddha",
"herbal",
"Diethyl nitrosamine"
],
"content": "Introduction\n\nHepatocellular carcinoma (HCC) is among the sixth most common and the second most lethal cancers. 1 It may occur as a sequel to chronic liver conditions such as alcohol and tobacco consumption, obesity, and infections like hepatitis B, hepatitis C, and aflatoxins. 2 , 3 These factors lead to liver inflammation and fibrosis, followed by the destruction of the normal liver architecture.\n\nChemotherapy, radiotherapy, radiofrequency ablation, hepatectomy, and transplantation are the management plans of HCC. 4 However, the survival rate is low, suggesting the need for improved therapy. 5 Chemotherapeutic agents used include sorafenib (MAP-kinase inhibitor), doxorubicin, 5-fluorouracil (5-FU), and cisplatin. 6 Being a multikinase inhibitor sorafenib, acts on vascular endothelial growth factor (VEGF) receptors, and prolongs survival so this drug is considered as a new reference standard for advanced HCC. However, it elicits adverse effects including skin toxicities, diarrhea, and hypertension, along with other general toxicities like anorexia, hair loss, weight loss, etc. 7\n\nCompared to conventional modes of treatment, plant-based medicines have generally fewer side effects, are cost-effective, and well tolerated by patients. 8 Kadukkai maathirai (KM) is an Indian traditional medicine prescribed by Siddha practitioners to treat edema in severe anemia and ascites secondary to liver disease. KM consists of Terminalia chebula Retz. (Combretaceae), Piper nigrum L. (Piperaceae), Eclipta alba L. (Asteraceae), Citrus L. (Rutaceae) and ferrous sulfate. 9 Each of the constituents mentioned is known to have a hepatoprotective effect. 10 T. chebula consists of gallic acid and chebulic acid; gallic acid has anti-inflammatory and antioxidant properties, whereas chebulic acid has antioxidant with hepatoprotective properties. 11 P. nigrum inhibits lipid peroxidation and superoxide free radical generation due to its antioxidant effect exerted by phenols and flavonoids. 12 , 13 Coumestans, present in E. alba, stimulates the regeneration of hepatocytes and protect the liver. 14\n\nThough Kadukkai maathirai is used for treating liver disorders by practitioners of Siddha medicine, yet its effect on hepatocellular carcinoma has not been explored. Diethylnitrosamine (DEN) is a known potential hepatocarcinogen that disrupts nuclear enzymes that help in the repair of DNA and replication. 14 In our previous study we demonstrated that the KM at the dose of 144 mg/kg treatment exhibited significant protection which was evident both by histology and biochemically against D-galactosamine-induced hepatic necrosis in rats. 15\n\nHepatic DEN metabolism produces O6-ethyl deoxyguanosine and O4- and O6-ethyl deoxythymidine, which are mutagenic and carcinogenic. 16 , 17 The effect of analyzed phytoconstituents of KM on low-density lipoprotein (LDL) receptor-related protein-6 (LRP6) and β-catenin signaling pathway, which play a role in hepatocellular carcinoma (HCC), was also studied in silico.\n\n\nMethods\n\nDiethylnitrosamine 0.01% (Catalogue number - D0516) from TCI chemicals, Tokyo, Japan, assay kits for liver function test from Spain-based Spinreact, silymarin 50mg/kg body weight/day (Item Number – 46791) from Micro Labs Limited, India, Kadukkai maathirai (MMP14013) from India-based SKM Siddha and Ayurveda (GMP certified) Company (India) Ltd. Good laboratory-grade chemicals were used.\n\nEthical statement: Seven-week-old female Sprague Dawley rats (150-200 g), procured from the Central Animal Research Facilities (CARF) of Kasturba Medical College, Manipal Academy of Higher Education, Manipal were used in the study after getting approval from the Institutional Animal Ethics Committee approval (IAEC/KMC/19/2016 dated 16.03.2016). Guidelines given by the Committee for Control and Supervision of Experiments on Animals (CCSEA), Government of India, New Delhi for the use of laboratory animals were followed for the maintenance of animals. 18 All efforts were made to ameliorate suffering of animals. All the rats were observed daily to check their health and ensure continuous access to food and water. Bedding in the cages were changed daily to provide healthy living conditions. The location of the animal cage was not changed throughout the study. The rats were acclimatized and maintained at 27 ± 3°C, humidity of 60 ± 10%, and a 12 h light/dark cycle. No procedures were done which would cause sustained pain. Anesthetics and the method of euthanasia used was as per guidelines of CCSEA.\n\nReporting Guidelines: The authors confirm that they followed and adhered to ARRIVE 2.0 Checklist for their study. ARRIVE CHECKLIST [Internet]. figshare; 2024 [cited 2024 Jun 7]. Available from: https://figshare.com/articles/dataset/ARRIVE_CHECKLIST/25910563/1. 76\n\nStudy design: The rats were randomised into 2 groups based on their body weight: normal control (n=6) and toxic control (n=30) rats.\n\nInduction of liver cancer: The number (n=6) of animals in each group was based on earlier study. 19 The groups were as follows: The normal control (group 1) consisted of a total of 6 rats and received drinking water for 16 weeks. The toxic control group (DEN) consisted of a total of 30 rats, which received DEN 0.01% for sixteen weeks through drinking water for induction of HCC. 20 At the end of 16 weeks, animals were divided into 5 groups (n=6/group) and received treatment orally as follows. Group 2- toxicant control and received gum acacia 2% 1 mL/kg orally for 4 weeks. 21 Group 3, 4, 5- test drug KM36, 72, 144 mg/kg body weight orally for 4 weeks respectively. 22 Group 6- received Silymarin (50 mg/kg body weight) orally for 4 weeks. 23\n\nAt the end of the study (total of 20 weeks) blood was drawn by retroorbital puncture. The animals of all groups were euthanised by administering pentobarbitone intraperitoneally in a dose of 200 mg/kg body weight, 24 then livers were dissected for histopathology and polyacrylamide gel electrophoresis.\n\n\n\n• Parameters to evaluate hepatoprotective potential of KM\n\nAfter 4 weeks of KM treatment, under ketamine anesthesia (50 mg/kg i.p), 25 blood was withdrawn from all the rats from each group to estimate the serum AST, ALT, ALP, bilirubin, and total protein levels using kits (Aspen Laboratory). 26\n\n• Parameters to evaluate whether KM has any anticancer effect\n\nDetermination of liver weight and nodule count\n\nThe liver of each animal was weighed and relative weight was calculated. The nodules on the liver were counted, and an intergroup comparison was made.\n\nDetermination of body weight\n\nWeight was measured at the end of study by using a metis electronic weighing balance. The weight difference was calculated.\n\nHistopathological evaluation\n\n10% formalin was used as the fixative. Paraffin-embedded wax blocks were prepared and the tissue section was prepared at 4μm thickness. The hepatic tissue was stained with hematoxylin-eosin and studied. 27 Regarding the animal group, the assessor was blinded.\n\nPolyacrylamide gel electrophoresis for the separation of proteins and mass spectrometry for the identification of proteins.\n\nSample Preparation and Electrospray-ionisation Quadrapole time of fight mass (ESI/QTOF) liquid chromatography and mass spectrometry analysis (LC-MS). Tissue extract was prepared, and proteins were separated by polyacrylamide gel electrophoresis. LC-MS analysis was used to identify the protein that was differentially expressed in response to DEN administration. The expressed protein was identified by coomassie staining, separated from PAGE gel, and subjected to LC-MS analysis using MASCOT Ver 2.3. 28\n\nIn-silico analysis of phytoconstituents of KM against β catenin and LRP6 in HCC\n\nThe binding mode and interaction of β catenin and LRP6-E3 with each of the derived list of phytoconstituents of Kadukkai maathirai was performed using AutoDock Vina software. 29 , 30 Grid boxes were set at two binding sites of the armadillo repeat region of β catenin and their XYZ coordinates include X: 107.640 Y: -29.892 Z: 1.991 Å and X: 102.640 Y: 9.850 Z: 29.741 Å respectively with a grid size of 40. Whereas the XYZ coordinates for LRP6-E3 were defined by establishing a grid box with the dimensions of X: -29.376 Y: 20.133 Z: -10.560 Å with a grid size of 40, The interactions of β catenin and LRP6 protein-ligand conformations, including hydrogen, and hydrophobic bonds along with their interacting residues were analyzed using BIOVIA Discovery Studio Visualizer. 31 The 2D structures of phytoconstituents present in KM were collected from the PubChem Compound database. A total of 19 structures were sketched, prepared, and saved in MDL mol format using ChemSketch 2019 2.2 32 and saved as PDBQT format. The 3D structure of β catenin (PDB ID: 1JPW) and LRP6 (PDB ID: 3S8V) were retrieved from Protein Data Bank (RCSB PDB), optimized, minimized their energy and saved as PDB format.\n\nAnalysis of extract using Gas chromatography-mass spectroscopy (GC-MS)\n\nIt was done with Shimadzu -QP2010. Column (30m length) used was RTX-5. Interface temperature 280 °C and ion source was 200 °C. Sample was injected (1 μL) for analysis and flow rate retained at 1 mL/minute. MS spectrum achieved was identified and compared with NIST library for confirmation of compounds. 33\n\nThe data of control, test drug control, and experimental groups were presented in the form of mean ± SD, and one-way ANOVA and post hoc Tukey's test (SPSS version 16) were performed. Statistical significance was considered at p<0.05.\n\n\nResults\n\nBiochemical estimation in serum\n\nSerum AST, ALP, ALT, and TBIL in DEN alone treated animals increased significantly in comparison to normal control indicating liver damage (Table 1). KM 36 mg/kg and KM72 mg/kg in DEN-treated groups showed a fall in the AST, ALT, ALP, and TBIL levels compared to animals that received DEN alone but it was not statistically significant. Other parameters were not affected significantly (Table 1).\n\n* p<0.05 versus control.\n\n# p<0.05 versus DEN.\n\n€ p<0.05 versus DEN+KM72 mg/kg.\n\n¥ p<0.05 versus DEN+Silymarin, (Values - Mean ±SD).\n\nBodyweight/Organ weight/Nodule count:\n\nBody weight decreased significantly and relative liver weight increased in the DEN-induced HCC group versus control. These were altered favorably(p<0.05) in DEN-treated rats who received KM 36, 72, 144 mg/kg, and silymarin as compared to DEN-alone treated rats (Table 2). A decrease (p<0.05) in nodule count in rats treated with KM 36 mg/kg, KM 72 mg/kg, and silymarin was observed in comparison to DEN group (Table 2, Figure 1).\n\n* p<0.05 versus control.\n\n# p < 0.05 versus DEN.\n\n€ p< 0.05 versus DEN+KM144.\n\n¥ p<0.05 versus DEN+KM72. Values: Mean±SD.\n\n1A (Normal control): Normal morphology of liver with smooth-surfaced hepatic lobes in the control animal. 1B (DEN): DEN alone administered group showed highly enlarged nodules with several foci on the surface of the liver and many greyish-white nodules, indicative of HCC. 1C (DEN +KM 36 mg/kg), 1D (DEN +KM 72 mg/ kg), 1E (DEN+KM 144 mg/kg), 1F (DEN + silymarin 50 mg/kg) groups showed relatively less foci on the hepatic surface and very few nodules when compared to 1B (DEN).\n\nFigure 2A, 2B (normal control): Showed normal liver structure, Figure 2C, 2D (DEN control): Showed an invasive tumor involving irregular nodules divided by thin fibrous septae and composed of solid sheets and broad trabeculae of neoplastic hepatocytes with round to polygonal cells, irregular nuclei, prominent nucleoli, vesicular chromatin, moderate to abundant granular eosinophilic cytoplasm, mitotic figures, scattered with numerous variably dilated sinusoids, flattened endothelial cells and focal bile pigments. The presence of many areas of high vascularity with several groups of cut sections of blood vessels and destruction of the typical pattern of hepatic cords/hepatocyte arrangement is indicative of hepatocellular carcinoma. Figures 2E, 2F (DEN+KM36), Figures 2G, 2H (DEN+ KM72), Figures 2I, 2J(DEN+KM144): The structure of liver looked normal with hexagonal hepatic lobules, a central vein in its center. However, there were areas showing features of HCC like well-vascularized tumours with thick trabeculae, distinct acinar pattern, some areas of vascular invasion, and signs of mild cytoplasmic vacuolar degeneration. However, the severity of the features of HCC in this group was very mild when compared with that of DEN. Figures 2K, 2L (DEN+ Silymarin): There were areas of mild cytoplasmic vacuolar degeneration and high vascularity indicative of HCC. But it was less when compared with that of DEN group. In general, there were normal liver tissues in large areas compared to the areas with features of HCC.\n\nLadder: Lanes (1–4) - normal control and test drug control groups; Lane 5 - DEN alone, Lanes 6–9 - DEN for 16 weeks followed by treatment with KM 36, 72 and 144 mg/kg, and silymarin, respectively. The protein lysate was prepared and subjected to separation by PAGE (Figure 3A). DEN control group had a band in the range of 25-30 kda as analysed by Polyacrylamide Gel Electrophoresis (PAGE). In comparison to lanes 5 and 6, band thickness was more in lanes 7, 8, and 9; this was confirmed by mass spectrometry and identified as GSTM1 (Figure 3B).\n\nThe molecular docking study revealed that nine phytoconstituents out of 19 made interactions with β catenin binding site that is residue number 219 to 335 (C-terminal helical region of Tcf-4interaction region) except D-allose which showed interactions between the residues 429 to 508 (extended region of Tcf-4 peptide interaction region) of β catenin. Their binding energies, number of interactions, and interacting residues of β catenin were tabulated in Table 3. The binding energies of the phytoconstituents ranged from -7.8 to -5.2 kcal/mol. The lowest binding energy was recorded for hexanediamide whereas, 2H-Pyran-2-one, 5,6-dihydro documented the highest among the shortlisted constituents. The phytoconstituents with interacting residues are displayed in Figure 4A and 4B as follows. Octadecadienoicacid and propylene glycol monooleate made a maximum number of interactions (8 each) whereas, Hexanediamide made the lowest number of interactions- 2 (Table 3). However, the constituents did not show any favorable interactions with the interaction site of LRP6-E3.\n\n(Left: binding poses; Right: 2D images) (< 5 Å distance).\n\n19 compounds were recognized by GC-MS from methanolic extract of KM. Piperine (66.26%) was the major constituent of KM. Others were D-Allose (4.97%), Propyleneglycol monoleate (4.68%), Levoglucosenone (3.15%), etc.\n\n\nDiscussion\n\nN-nitroso compounds, as potential carcinogens, were first brought to the public attention as a cause of liver disease in 1937. In 1954, it was confirmed that one oral or parenteral dose of DEN (20-40 mg/kg) acts as a liver toxin, leading to severe liver necrosis in rodents. 34 , 35 In rodents, chronic parenteral and oral administration of DEN at large doses effectively induces liver tumour. 36 Pericentral foci of small dysplastic liver cells is induced by diethylnitrosamine (DEN), by ethylating DNA 37 , 38 leading to cirrhosis and multifocal HCC. 39 It predominantly targets the liver, where it is biologically transformed by CYP450-dependent processes that are most active in centrilobular hepatocytes. 40 The main metabolising pathways of DEN in rodents and humans are very similar. 41 which results in reactive species responsible for the development of methylated compounds, leading to carcinogenesis. Previous studies have shown that in DEN-treated group, there was distorted liver architecture with swollen cells; hyperplasia, and dysplasia, with infiltration of inflammatory cells, indicating carcinogenesis. 42 – 44 In the present study, similar histopathological changes occurred in DEN-treated groups.\n\nDEN-induced hepatic injury leads to instability of metabolism by the liver with concomitant variations in the activities of enzymes. 45 An increase in the level of transaminases indicates liver damage. Liver toxicity leads to the breakdown of the cell membrane and further spillage of the aminotransferases from the cytoplasm into the serum, thus increasing the serum aminotransferase levels. 46 Aminotransferases are known as diagnostic and reliable markers of liver damage. In our study, the level of liver enzymes and bilirubin were increased significantly reflecting liver damage. There was a decrease in albumin levels of DEN alone treated rats. In rats which received DEN with KM, the enzyme levels were reduced when compared to DEN alone treated rats, though it was not statistically significant. Probably, increasing the duration of treatment (> 4 weeks) with KM might show a better improvement in liver functions.\n\nWeight loss is an important symptom of DEN-induced cancer. DEN causes alterations which are well-matched with the worsening of liver function during pathogenesis of liver fibrosis. 47 Administration of KM in varying doses following induction of HCC by DEN prevented body weight loss significantly (p<0.05) which could be due to herbal constituents of KM.\n\nIn this study, the relative liver weights of DEN-treated rats were significantly high compared to normal. Treatment with KM prevented an increase in liver weight, which has been commonly observed and reported in liver cancer. 48 DEN gets metabolized by microsomal enzymes in a sequence of intermediate responses leading to development of mutagenic metabolites. The free radicals generated in the process trigger cell proliferation, appearance of liver nodules and a rise in the weight of the liver. 49 Low levels of ROS do not cause any damage to the cell process, but high ROS level damages proteins, lipids and DNA by nonspecific process. 50 Glutathione-S transferase mu 1 (GSTM1) is a phase II detoxifying enzyme. It plays a role in the detoxification of environmental carcinogen metabolites, suggesting that its downregulation may contribute to HCC carcinogenesis secondary to ROS-facilitated oxidative damage. 51 The expression of GSTM1 was much higher in the KM and silymarin treatment groups versus control and DEN groups.\n\nSriram Seshadri et al. first demonstrated the antiproliferative property of Eclipta alba in HepG2 cell lines. Eclipta alba extract could induce DNA fragmentation and thus apoptosis in hepatic cell lines. 52 Alkaloids present in Eclipta alba can damage the DNA of cancer cells. 53 Eclipta alba is a well-known liver regenerative herb and it has protective effect on liver parenchymal cells and its cell membrane resulting in a decrease in enzyme seepage. 54\n\nThe important constituent of Terminalia chebula is chebulic acid. 55 Chebulic acid has been established to have biological actions such as hepatoprotective and antioxidant effects in various liver disease models. 56 In a previous study, Terminalia chebula extract (TCE) stimulated apoptosis with membrane bleb and apoptotic bodies; hence it rendered protection to macromolecules in DEN model by stabilizing the redox balance. 57\n\nPiperine has demonstrated dose-dependent cytotoxicity against Hep G2 cells. It inhibits catalase and induces mitochondria-mediated cell death by H2O2 in these cells. Further, analysis revealed that it had receptor tyrosine kinase inhibition property and this led to inhibition of HCC progression. 58\n\nGlucose, a major source of energy for cancer cells, is transported into cells via glucose transporters (GLUTs). These transporters are overexpressed in cancer cells which helps in enhanced glucose uptake by the cancer cells. Studies have shown that D-allose inhibited GLUT1 expression in cell lines of hepatocellular carcinoma thus reducing glucose utilization by cancer cells. 59\n\nCitrus fruits contain valuable bioflavonoids that have bioactivities on apoptosis induction in vitro. 60 The phytochemicals present in citrus fruits exhibit antioxidant, anticancer, and anti-inflammatory activities. 61 , 62 Hesperidin has shown to cause HepG2 cell death in a dose-dependent manner. Its molecular targets include Bcl-2, Bax, caspases for apoptosis induction and matrix metalloproteinase-2, cyclooxygenase-2 and MMP-9 for metastasis and angiogenesis suppression. 63 The constituent plants of KM could have exerted synergistic effects resulted in prevention of the progression of HCC.\n\nβ catenin is a multifunctional protein in Wnt signalling pathway and Tcf4 is a peptide that interacts with the armadillo repeat region of β catenin. This complex is essential to produce downstream transcription factors for eventual malignant growth. The Tcf4 interaction regions on β catenin have been studied and used as templates for analysis. 64 , 65 Among the phytoconstituents of KM, D-allose contributed a maximum number of hydrogen interactions-4 with Lys435, His470. Octadecadienoicacid and propylene glycol monooleate showed the maximum number of interactions of eight with one hydrogen interaction. All other phytoconstituents showed interactions with this region of β cateninarr. With this analysis, we hypothesize that these constituents could interact with this region simultaneously or in part modulate the transcription process by preventing Tcf4 interaction with β catenin. 64 , 65 We also noted that the shortlisted constituents would not modulate the LRP6-DKK1 mediated Wnt stimulation and subsequent pathway activation as they did not make any interactions with the LRP6-E3 binding site. We presume that the active phytoconstituents of Kadukkai maathirai could modulate the intracellular transcription process by inhibiting the armadillo repeat region of β catenin.\n\n\nConclusions\n\nKadukkai maathirai in doses of 36 mg/kg and 72 mg/kg favourably altered most of the parameters like nodule count, relative liver weight, body weight and histopathology in HCC-induced rats. Hence, it could be concluded that the collective effect of all the herbs present in KM was responsible for its beneficial effect. Interaction of its phytoconstituents with β catenin could have resulted in modulation of the nuclear level transcription with beta-catenin and TCF complex which could prevented the progression of hepatocellular carcinoma in rats. It appears that KM has the potential to be used as a supplement in the management of HCC. Further complete studies are required to explore the hepatoprotective mechanism of KM against Diethyl nitrosamine-induced HCC.\n\n\nEthics statement\n\nSeven-week-old female Sprague Dawley rats (150-200 g) procured from the Central Animal Research Facilities (CARF) of Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal were used in the study after getting approval from the Institutional Animal Ethics Committee approval (IAEC/KMC/19/2016 dated 16.03.2016). Guidelines given by the Committee for Control and Supervision of Experiments on Animals, Government of India, New Delhi for the use of laboratory animals were followed for the maintenance of animals. 18",
"appendix": "Data availability\n\n\n\n• Figshare: Macroscopic appearance of the liver https://doi.org/10.6084/m9.figshare.25117424.v1 66\n\n• Figshare: Histopathology https://doi.org/10.6084/m9.figshare.25117436.v1 67\n\n• Figshare: Polyacrylamide Gel Electrophoresis for the separation of proteins and mass spectrometry for the identification of proteins https://doi.org/10.6084/m9.figshare.25117442.v1 68\n\n• Figshare: In-silico analysis of interactions of phytoconstituents of KM with β catenin https://doi.org/10.6084/m9.figshare.25117454.v1 69\n\n• Figshare: Gas chromatography-mass spectroscopy (GC-MS) analysis of test drug KM https://doi.org/10.6084/m9.figshare.25117460.v1 70\n\n• Figshare: Effect of KM on liver function in DEN-induced HCC model in rats https://doi.org/10.6084/m9.figshare.25117469.v1 71\n\n• Figshare: Effect of “KM on body weight, relative weight of liver and nodule count in DEN-induced hepatocellular carcinoma model in rats https://doi.org/10.6084/m9.figshare.25117484.v1 72\n\n• Figshare: Shortlisted phytoconstituents and their interactions with β catenin https://doi.org/10.6084/m9.figshare.25117490.v1 73\n\n• Figshare: Gas chromatography-mass spectroscopy (GC-MS) analysis of the test drug Kadukkai maathirai (KM) https://doi.org/10.6084/m9.figshare.25117493.v1 74\n\n• Figshare: Raw Data https://doi.org/10.6084/m9.figshare.25815934.v1 75\n\nFigshare: ARRIVE checklist for Kadukkai maathirai (Indian herbal drug) prevents hepatocellular cancer progression by enhancing GSTM1 expression and modulating β catenin transcription: in-silico and in-vivo study https://doi.org/10.6084/m9.figshare.25910563.v1 76\n\n(Shetty MS. ARRIVE CHECKLIST [Internet]. figshare; 2024 [cited 2024 Jun 7]. Available from: https://figshare.com/articles/dataset/ARRIVE_CHECKLIST/25910563/1)\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 Manipal Academy of Higher Education, Manipal for providing the facilities to carry out the research.\n\n\nReferences\n\nMcGlynn KA, Petrick JL, London WT: Global Epidemiology of Hepatocellular Carcinoma: An Emphasis on Demographic and Regional Variability. Clin. Liver Dis. 2015; 19: 223–238. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSingal AG, El-Serag HB: Hepatocellular Carcinoma From Epidemiology to Prevention: Translating Knowledge into Practice. Clin. Gastroenterol. Hepatol. 2015; 13: 2140–2151. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSachdeva M, Chawla YK, Arora SK: Immunology of hepatocellular carcinoma. World J. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nLu Y, Zhou J, Zhang J, et al.: Dual roles of glutathione S-transferase mu 1 in the development and metastasis of hepatocellular carcinoma. Biomed. Pharmacother. 2019; 120: 109532. Publisher Full Text\n\nChaudhary H, Dhuna V, Singh J, et al.: Evaluation of hydro-alcoholic extract of Eclipta alba for its anticancer potential: An in vitro study. J. Ethnopharmacol. 2011; 136(2): 363–367. PubMed Abstract | Publisher Full Text\n\nAbdel-Kader MS, Bahler BD, Malone S, et al.: DNA-damaging steroidal alkaloids from Eclipta alba from the suriname rainforest. J. Nat. Prod. 1998; 61: 1202–1208. PubMed Abstract | Publisher Full Text\n\nChaudhary H, Jena PK, Seshadri S: In Vivo Evaluation of Eclipta alba Extract as Anticancer and Multidrug Resistance Reversal Agent. Nutr. Cancer. 2014; 66(5): 904–913. Publisher Full Text\n\nJuang LJ, Sheu SJ, Lin TC: Determination of hydrolyzable tannins in the fruit ofTerminalia chebula Retz. by high-performance liquid chromatography and capillary electrophoresis. J. Sep. Sci. 2004; 27(9): 718–724. PubMed Abstract | Publisher Full Text\n\nLee HS, Jung SH, Yun BS, et al.: Isolation of chebulic acid from Terminalia chebula Retz. and its antioxidant effect in isolated rat hepatocytes. Arch. Toxicol. 2007; 81: 211–218. PubMed Abstract | Publisher Full Text\n\nSrigopalram S, Jayraaj IA: Effect of Terminalia chebula Retz on den induced hepatocellular carcinogenesis in experimental rats. Int. J. Pharm. Pharm. Sci. 2012.\n\nGunasekaran V, Elangovan K, Niranjali DS: Targeting hepatocellular carcinoma with piperine by radical-mediated mitochondrial pathway of apoptosis: An in vitro and in vivo study. Food Chem. Toxicol. 2017; 105: 106–118. 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Publisher Full Text\n\nRoohbakhsh A, Parhiz H, Soltani F, et al.: Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases. Life Sci. 2015; 124: 64–74. PubMed Abstract | Publisher Full Text\n\nCheng Z, Biechele T, Wei Z, et al.: Crystal structures of the extracellular domain of LRP6 and its complex with DKK1. Nat. Struct. Mol. Biol. 2011; 18(11): 1204–1210. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPoy F, Lepourcelet M, Shivdasani R, et al.: Structure of a human Tcf4–β-catenin complex. Nat. Struct. Mol. Biol. 2001; 8: 1053–1057. PubMed Abstract | Publisher Full Text\n\nShetty MS: Macroscopic appearance of the liver.April 2024. Publisher Full Text\n\nShetty MS: Histopathology.April 2024. Publisher Full Text\n\nShetty MS: Polyacrylamide Gel Electrophoresis for the separation of proteins and mass spectrometry for the identification of proteins.April 2024. Publisher Full Text\n\nShetty MS: In-silico analysis of interactions of phytoconstituents of KM with β catenin.April 2024. Publisher Full Text\n\nShetty MS: Gas chromatography-mass spectroscopy (GC-MS) analysis of test drug KM.April 2024. Publisher Full Text\n\nShetty MS: Effect of KM on liver function in DEN-induced HCC model in rats.April 2024. Publisher Full Text\n\nShetty MS: Effect of “KM on body weight, relative weight of liver and nodule count in DEN-induced hepatocellular carcinoma model in rats”.April 2024. Publisher Full Text\n\nShetty MS: Shortlisted phytoconstituents and their interactions with β catenin.April 2024. Publisher Full Text\n\nShetty MS: Gas chromatography-mass spectroscopy (GC-MS) analysis of the test drug Kadukkai maathirai (KM).April 2024. Publisher Full Text\n\nShetty MS: Raw Data.2024.\n\nShetty MS: ARRIVE CHECKLIST.June 2024. Publisher Full Text"
}
|
[
{
"id": "309885",
"date": "21 Aug 2024",
"name": "Haiyang Yu",
"expertise": [
"Reviewer Expertise hepatocellular cancer progression"
],
"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 article demonstrates that KM can protect the liver from further damage by reducing the nodule count and reducing the relative weight of the liver. Also, this paper verifies that KM regulates the intracellular transcription process by reducing GSTM1 expression and simultaneously inhibiting the armadillo repeat region of β catenin to realize the potential of inhibiting HCC. But the hepatoprotection mechanism of KM against diethylnitrosamine-induced liver cancer needs to be further improved. It suggest that the author should further study and explain. The arrangement of the pictures, tables, and text in the article is too messy. For example, Figure 5 and Table 4, it is recommended to arrange them separately. We recommended that the picture and tables should be placed above or below the page for reading. In some similar paper, some cell experiments will be done to verify the results obtained in animal experiments. We suggest that the author can do some cell experiments to further study. Page 16, conclusions, “Hence, it could be concluded that the collective effect of all the herbs present in KM was responsible for its beneficial effect.” The description is just too absolute. Please unify the cell line names included in the article. For example, page 15，HepG2 cell and Hep G2 cells.\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": "309884",
"date": "21 Aug 2024",
"name": "Talha Bin Emran",
"expertise": [
"Reviewer Expertise Postdoctoral scientist with 2+ years of experience in viral and non-viral gene editing",
"particularly using the CRISPR/Cas9 system and DNA Damage Repair (DDR) in cancer biology. Proficient in handling mammalian cancer cells",
"conducting cell viability assays",
"and performing advanced molecular techniques such as next-generation sequencing. Actively engaged in researching DDR gene targets to overcome cancer therapy resistance. Prepared to contribute to the academic",
"pharmaceutical",
"biotech",
"and translational research sectors",
"focusing on gene therapy",
"gene editing",
"immune-oncology",
"mRNA",
"oncological biomarkers",
"and the development of small molecule/DDR-targeted inhibitors. Possesses a strong foundation in the practical applications and potential of small molecule inhibitor screening."
],
"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 results and discussion section could benefit from a more detailed exploration of the findings. It would be helpful to provide additional insight into why certain effects are coming in to existence and what could be the possible reason behind them? 2. Results and Conclusion: The section devoted to the explanation of the results suffers from the same problems revealed so far. The storyline in the results section (and conclusion) is hard to follow. Moreover, the conclusions presented appear to diverge from the insights suggested by the empirical results. It may be beneficial to revisit and align the conclusions more closely with the findings. 3. The discussion should be rather organized around arguments avoiding simply describing details without providing much meaning. A real discussion should also link the findings of the study to theory and/or literature.\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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-639
|
https://f1000research.com/articles/13-658/v1
|
18 Jun 24
|
{
"type": "Systematic Review",
"title": "Transcutaneous stimulation as a niche theme in gastroparesis therapy",
"authors": [
"ARMAN YURISALDI SALEH",
"Riezky Valentina",
"Dwi Arwandi Yogi Saputra",
"Riezky Valentina",
"Dwi Arwandi Yogi Saputra"
],
"abstract": "Introduction Gastroparesis is a condition characterized by the accumulation of bile salts. It is prevalent globally, with a global prevalence of 0.9% and 1.3% in individuals with diabetes. New techniques for diagnosing gastroparesis, such as bile salt titration and nitric oxide sulfate, can improve patient care. However, simptomatic control is needed to increase gastric salts, reduce inflammation, and control potential diseases. Gastroparesis can cause complications like weight loss, malnutrition, and gastrointestinal changes that cannot be predicted. Neurological techniques like gyroscope stimulation and endoscopy (G-POEM) can help diagnose refractive gastroparesis. Interdisciplinary collaboration is crucial in addressing gastroparesis issues, and bibliometric research is essential for finding effective new treatments.\n\nMethods In this work, a literature review methodology is employed to gather data from the Scopus database using the keywords neuroaid. Data were analyzed using Biblioshiny and VOSviewer software to produce visualizations and bibliometric maps. We conducted quantitative and qualitative analysis.\n\nResults The research trend found are documents by year, most relevant sources, factorial map of the most cited documents, factorial map of The documents with the highest contributes, documents by author, documents by country or territory, documents by subject area, documents by affiliation, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map, thematic evolution, cluster analysis, topic dendogram, and country collaboration map.\n\nConclusions The study on gastroparesis identifies key themes such as diet modification, glucose control, and medication therapy. It also discusses the role of Cajal in smooth muscle concentration, common causes of gastroparesis, and transcutaneous stimulation. The study also explores motorcycle themes, such as the vagus nerve, and emerging themes like devices and electronics. Basic themes include gastrointestinal disorders, neuromodulation, patients, diabetes, and gastric electrical stimulation. Management involves multidisciplinary approaches, lifestyle changes, medication therapy, and bedtime interventions.",
"keywords": [
"gastroparesis",
"niche",
"therapy",
"nerve",
"stimulation",
"bibliometric"
],
"content": "Introduction\n\nA disorder called gastroparesis is characterized by a delayed stomach emptying.1–3 The global prevalence of gastroparesis-like symptoms (GPLS) was 0.9% overall and 1.3% among individuals with diabetes.1,2 In the US, the prevalence of gastroparesis is estimated to be approximately 267.7 per 100,000 adults.1,2\n\nGastroparesis is usually diagnosed based on clinical symptoms and delayed gastric emptying demonstrated by imaging tests.1–3 New techniques for assessing gastric emptying, such as the gastric emptying breath test and wireless motility capsules, allow clinicians to better characterize their patients.2\n\nThe goals of symptomatic control, notwithstanding the limitations of existing treatments, are to improve stomach emptying, reduce nausea and vomiting, and manage related abdominal discomfort.4 Other possible treatments target bacterial overgrowth, enhance stomach accommodation or pyloric dysfunction, and lessen acid production.4\n\nGastroparesis can cause complications such as severe dehydration, malnutrition, and unpredictable blood sugar changes.5\n\nGastric electrical stimulation (GERD) and oral endoscopic pyloric myotomy (G-POEM) are some of the neurological techniques that can help treat refractory gastroparesis.6\n\nFinding the right therapy for gastroparesis is essential because it can improve the patient's quality of life and reduce complications associated with this condition.2,4\n\nCollaboration between interdisciplinary scientists is very important in overcoming the problem of gastroparesis. An interdisciplinary approach allows professionals to approach patient care from multiple perspectives.1\n\nBibliometric research is essential in the search for effective new therapies. By analyzing scientific publications in this field, researchers can identify research trends and discover areas that require further research.1,2\n\n\nMethods\n\nBibliometric research is a research method that uses scientific publication data to describe and analyze the development of a field of science. This research aims to identify and map trends, patterns, and relationships between scientific documents related to certain topics. In this research, the topic chosen was gastroparesis, therapy, and “nerve stimulation”. This research uses data from the website www.scopus.com, which is one of the largest and most trusted databases for scientific publications. This research was conducted on early June 2024.\n\nTo carry out bibliometric research, the steps to follow are as follows:\n\n1. Determine search keywords. In this research, the keywords used are gastroparesis, therapy, and “nerve stimulation”. These keywords are entered into the search column on the www.scopus.com site by selecting the topic field (title, abstract, keywords).\n\n2. Filter search results. In this study, were not filtered.\n\n3. Get data from search results. In this study, search result data is retrieved in three different formats:\n\n• CSV (comma-separated value), which includes the title, author, affiliation, year, source, abstract, and keywords, among other basic document information.\n\n• The Research Information System (RIS), which offers comprehensive details on a document, including the references it cites.\n\nIn this study we found are documents by year has been an increase in the number of documents; until 2023, there were 5 documents, most relevant sources is journal of neurogastroenterology and mobility, factorial map of the most cited documents following is a summary of a study entitled Bioelectric neuromodulation for gastrointestinal disorders: effectiveness and mechanisms by Payne SC, published in the journal Nature Reviews Gastroenterology & Hepatology, Factorial map of the documents with the highest contributes entitled Clinical trial: interferential electric stimulation in functional dyspepsia patients: a prospective randomized study by Koklu S, published in the journal Alimentary Pharmacology & Therapeutics.\n\nDocuments by author with 5 documents are Yin, J., documents by country or territory is United States is the country with the largest number of document producers 46 documents, documents by subject area, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map based on the title shows that the niche theme is the keyword mitochondria signaling pathway, effects neuroprotective effect, dan oxidative stres toxicity, thematic evolution, cluster analysis, qualitative analysis, and word cloud.\n\nWe used the following terms to do a search on the Scopus website, taking into consideration that this website contains research that is considered to be valid: TITLE – ABS – KEY (gastroparesis) AND TITLE – ABS – KEY (therapy) AND TITLE – ABS – KEY (“nerve stimulation”) are the titles of the products that are under consideration. fifty-nine documents were received by us. We then save the document from Scopus in the form of a file with the extension.csv file following this step.\n\nBoth the Biblioshiny and Vosviewer software packages were utilised in the analysis process.\n\nDocuments by year\n\nBased on Figure 1, it appears that there has been an increase in the number of documents, until in 2023 there were 5 documents. The oldest document in 2002 was entitled Gastric electrical stimulation in intractable symptomatic gastroparesis., written by Abell, T. L et al.,7 Next is the article entitled Physiology and pathophysiology of the interstitial cells of cajal: From bench to bedside VI. Pathogenesis and therapeutic approaches to human gastric dysrhythmias written by Owyang, C., and Hasler, W.L.8 Meanwhile, the latest document in 2024 is entitled F Non-invasive neuromodulation: an emerging intervention for visceral pain in gastrointestinal disorders written by Alam, M.J. and Chen, J.D.Z.9 Next is the article entitled Transcutaneous electrical stimulation for gastrointestinal motility disorders written by Song, G. et al,10 next article is Gastric peroral endoscopic myotomy for management of refractory gastroparesis in patients with gastric neurostimulator devices: a multicenter retrospective case control study written by Ichkhanian, Y. et al.11 next article is Electroceuticals for Neurogastroenterology and Motility Disorders written by Jiang, Y. and Soffer, E.12 And next article is Noninvasive electrical neuromodulation for gastrointestinal motility disorders written by Yin, J. and Chen, J.D.Z.13\n\nMost relevant sources\n\nBased on Figure 2, the following are the journals that publish the most important documents: The first is neurogastroenterology and mobility. This journal has been indexed in Scopus. The Journal of Neurogastroenterology and Motility is published by Wiley-Blackwell Publishing Ltd. The SJR (Scientific Journal Rankings) for Neurogastroenterology and Motility in 2023 is 0.944. The H-index for neurogastroenterology and mobility is 126. This journal accepts articles that focus on the fields of gastroenterology and neurology, especially those related to gastrointestinal motility. Some topics that frequently appear in publications in this journal include, but are not limited to, the pathophysiology and treatment of gastroparesis, esophageal smooth muscle phenotype in achalasia, retrograde cricopharyngeus dysfunction, and the effects of trimebutine and rifaximin on glucose breath testing in patients with functional bloating.\n\nIn second place is the journal Neuromodulation. This journal has been indexed in Scopus. The Journal of Neuromodulation is published by Elsevier on behalf of the International Neuromodulation Society. The SJR (Scientific Journal Rankings) for neuromodulation in 2023 is 0.827. The H-index for neuromodulation is 77. This journal accepts papers focused on the field of neuromodulation, including clinical, translational, and basic research. Some topics that frequently appear in this journal's publications include, but are not limited to, pain, headaches, movement disorders, spasticity, paralysis, psychiatric disorders, epilepsy, sensory deprivation, gastric dysfunction, obesity, and incontinence.\n\nIn third place is the American Journal of Physiology—Gastrointestinal. This journal has been indexed in Scopus since 1980. The American Journal of Physiology—Gastrointestinal is published by the American Physiological Society. The SJR (Scientific Journal Rankings) for the American Journal of Physiology-Gastrointestinal in 2023 is 1,383. The H-index for the American Journal of Physiology-Gastrointestinal is 191. Original research on any area of the gastrointestinal tract, hepatobiliary system, or pancreas, whether normal or pathological, is welcome to be published in this publication. Manuscripts pertaining to these organs' growth and development, digestion, secretion, absorption, metabolism, and motility are all welcome, as are research reports on immune and inflammatory processes, as well as those involving neural, endocrine, and circulatory control mechanisms.\n\nFactorial map of the most cited documents\n\nBased on Figure 3, the following is a summary of a study entitled Bioelectric neuromodulation for gastrointestinal disorders: effectiveness and mechanisms by Payne SC, published in the journal Nature Reviews Gastroenterology & Hepatology.14\n\nThis study examines the use of electrical stimulation of nerves or brain centers as a therapeutic tool being tested in a variety of human diseases, including Parkinson's disease, arthritis, depressive disorders, schizophrenia, pain, and bladder dysfunction.14\n\nNeuromodulation, bioelectrical neuromodulation, or electroceuticals are terms used to describe this therapy. The clinical community is very interested in the potential application of bioelectric neuromodulation to treat gastrointestinal-related illnesses, and several gastrointestinal tract sites have been studied for a variety of conditions.14\n\nIn many cases, The variability of outcomes and the lack of clarity around mechanisms of action pose significant therapeutic problems (such as the ideal stimulus settings) that have already been discussed in other reviews. Sacral nerve stimulation for fecal incontinence is still the sole widely utilized neuromodulation protocol for gastrointestinal problems, despite the fast advancements in bioelectrical neuromodulation technology during the past ten years.14\n\nSuccess rates for treating various ailments like IBD, obesity, nausea, and gastroparesis have varied. By gaining more insight into the targeted brain circuits and their physiological and pathological roles, improving stimulation protocols, and identifying the patients who would benefit most from these therapies, the therapeutic effectiveness of these bioelectric neuromodulation therapies may be increased.14\n\nFactorial map of the documents with the highest contributes\n\nIn Figure 4, the following is a summary of the study entitled Clinical trial: interferential electric stimulation in functional dyspepsia patients: a prospective randomized study by Koklu S, published in the journal Alimentary Pharmacology & Therapeutics.15\n\nThis study aimed to analyze if transcutaneous electrical stimulation is a treatment that works for patients with functional dyspepsia. Functional dyspepsia patients were randomly assigned to vacuum interference flow (IFC) and placebo groups. Both treatments consisted of 12 sessions given over 4 weeks.15\n\nThe outcomes demonstrated that while heartburn and vomiting did not significantly change in the placebo group, all symptoms in the therapy group—aside from early satiety—improved during and after treatment sessions. During treatment sessions, it was demonstrated that IFC therapy was more effective than placebo in terms of pyrosis, bloating, early satiety, and post-meal satiety.15\n\nVacuum IFC was demonstrated to be more effective than a placebo one month following the treatment session in terms of early satiety and stomach ulcers. To sum up, vacuum IFC is a successful, non-invasive treatment for functional dyspepsia. Patients with drug-resistant functional dyspepsia may benefit from a novel kind of treatment called transcutaneous electrical stimulation.15\n\nDocuments by author\n\nBased on Figure 5. the most authors with 5 documents are Yin, J., with the titles of several articles, namely: A novel approach in spinal cord stimulation for enhancing gastric motility: A preliminary study on canines, Emerging Gastric Stimulation for Dysmotility Disorder and Obesity, Electrical therapies for gastrointestinal motility disorders, Ameliorating effect of transcutaneous electroacupuncture on impaired gastric accommodation induced by cold meal in healthy subjects, and Gastric neuromodulation with Enterra system for nausea and vomiting in patients with gastroparesis.16–20\n\nThe next most author with 4 documents is Chen, J.D.Z., with the titles of several articles, namely: A novel approach in spinal cord stimulation for enhancing gastric motility: A preliminary study on canines, Electrical therapies for gastrointestinal motility disorders, Gastric neuromodulation with Enterra system for nausea and vomiting in patients with gastroparesis, and Effects and mechanisms of electrical stimulation of the stomach, duodenum, ileum, and colon on gastric tone in dogs.16,18,20,21\n\nThe next most author with 4 documents is McCallum, R.W., with the titles of several articles, namely Surgical approaches to treatment of gastroparesis: Gastric electrical stimulation, pyloroplasty, total gastrectomy and enteral feeding tubes, Gastric neuromodulation with Enterra system for nausea and vomiting in patients with gastroparesis, Treatment of Refractory Gastroparesis: Gastric and Jejunal Tubes, Botox, Gastric Electrical Stimulation, and Surgery, and Gastrointestinal Electrical Stimulation for Treatment of Gastrointestinal Disorders: Gastroparesis, Obesity, Fecal Incontinence, and Constipation.20,22–24\n\nDocuments by country or territory\n\nBased on Figure 6, the United States is the country with the largest number of document producers 46 documents. Followed by Canada with 4 documents, China with 4 documents, and Germany with 3 documents.\n\nDocuments by subject area (Table 1, Figure 7)\n\nDocuments by affiliation\n\nBased on Figure 8, in first place, the producer of the most documents is affiliated with the John Hopkins University with 5 documents, next in second place is affiliated with John Hopkins University School of Medicine with 4 documents and next is the Texas Tech University Health Sciences Center with 4 documents.\n\nNetwork visualization\n\nBased on Figure 9, it can be seen that the areas studied are still not related to other areas that are divided into edges. That field is: stomach motility, electrode, electrodes implanted, diabetic stomach paresis, heart arrhythmia, diet therapy, animal experiment, irritable colon, and gabapentin.\n\nOverlay visualization of scopus, database using Vosviewer\n\nBased on Figure 10. In the overlay visualization, it appears that the keywords that are being researched a lot approaching 2018 are the parts colored yellow, namely: diabetic stomach paresis, abdominal pain, physiology, procedures, electrotherapy, innervation, neuromodulation, sacral nerve stimulation, gastrointestinal disease, and gastrointestinal diseases.\n\nDensity visualization\n\nBased on Figure 11. In the visual circulation density, it appears that the part that is already saturated with research is yellow, while the part that is not yet saturated is slightly yellow and dominantly green, namely keywords: clinical article, stomach motility, young adult, electrodes implanted, electrode, animal experiment, diabetic stomach paresis, major clinical study, abdominal pain, diabetes mellitus, physiology, animals, disease severity, therapy effect case report, antiemetic agent, pyloroplastu, prokinetic agent, pyloromyotomy, gastrecromy, tegaserod, domperidone, clinical feature, cisapride, heart arrhtymia, diet therapy, gabapentin, prevalence, electrostimulation therapy, dyspepsia, irritable colon, gastrointestinal motility diso, gastrointestinal disease, gastrointestinal diseases. Sacral nerve stimulation, gastrointestinal tract, neuromodulation, electroacunpuncture, intestine innervation, innervation, animal, animals, and gastrointestinal motility.\n\nThematic map\n\nBased on Figure 12, Based on the thematic map, it can be explained as follows: Upper Left Quadrant (Niche and Emerging/Declining Themes): This quadrant contains keywords such as “pain,” “transcutaneous,” “prospective clinical study,” and “cable approaches.” This indicates a focus on innovative clinical studies related to pain management via transcutaneous methods.\n\nTop Right Quadrant (Motor and Emerging/Declining Themes)*: This quadrant is empty, indicating that there may be little innovation currently or waning interest in this area. Bottom Left Quadrant (Niche and Basic Themes)*: This quadrant includes keywords such as “arterra electronic devices,” indicating a focus on electronic devices in the context of medical applications that are considered niche but basic.\n\nLower Right Quadrant (Motor and Basic Themes): This quadrant represents basic motor themes with keywords such as “vagal nerve emerging,” “gastric electrical stimulation,” and larger keyword clusters including “diabetic gastroparesis” and “gastrointestinal neuromodulation.\" This represents an established medical practice that focuses on electrical stimulation for conditions such as diabetic gastroparesis.\n\nEach keyword or keyword cluster provides insight into a specific area of medical research or practice, indicating what is currently niche or basic and what is considered emerging or declining within this thematic area.\n\nThematic evolution\n\nBased on Figure 13, There was an evolution of changes in themes in research in 2002–2016 with the keywords motility, gastrointestinal, diabetic, gastroparesis, and prospective. The theme then changed in 2017–2023 to gastrointestinal, stimulation, gastroparesis, and management.\n\nTopic dendogram\n\nBased on Figure 14. There are 2 large clusters based on keywords. There are 2 clusters of blue and red.\n\nCountry collaboration map\n\nBased on Figure 15. Intense cooperation in this field is only carried out by China and the United States.\n\n\nDiscussion\n\nThe most important thing in bibliometric studies on the topic of gastroparesis therapy with nerve stimulation is to look for niche themes and map things that researchers have started to leave behind.\n\nThe following is a more detailed and sequential explanation of the keywords in the thematic map:\n\nNiche Themes\n\nThe approach to treating gastroparesis involves a variety of strategies, including diet modification, blood glucose control, and pharmacologic therapy with prokinetics and antiemetics.41,66,70\n\nCajal refers to the Interstitial Cells of Cajal (ICC), which act as pacemaker cells in the digestive tract and play an important role in coordinating smooth muscle contractions. Disruption or loss of ICC has been associated with several GI motility disorders, including gastroparesis.66\n\nPain is a common symptom of gastroparesis. The pain usually occurs in the upper abdominal area and can vary from dull to sharp.37\n\nTranscutaneous refers to therapy that involves nerve stimulation through the skin without the need for surgery. In the context of gastroparesis, transcutaneous therapies such as transcutaneous vagus nerve stimulation have been investigated and show potential for reducing symptoms.66,70\n\nIn the context of gastroparesis, accommodation refers to the stomach's ability to relax and adjust to the volume of incoming food. Impairments in gastric accommodation may contribute to the symptoms of gastroparesis.41,66\n\nMuch research has been and is being conducted to better understand this condition and develop more effective therapies.43,57\n\nIn the context of medical research, a prospective study is a type of research that follows subjects over time to observe specific outcomes. Prospective studies are often used in gastroparesis research to better understand how this condition develops and responds to therapy.37,66\n\nThe vagus nerve is a cranial nerve that plays an important role in various body functions, including the control of muscle movements in digestion. In the context of gastroparesis, damage to the vagus nerve can cause delayed gastric emptying.37,41 Some therapies in development include relamorelin, prucalopride, and aprepitant.41,66,70\n\nThe word devices may refer to the tools or devices used in gastric electrical stimulation therapy. However, more specific information may require further research.41,66,70\n\nThe word electronic may refer to the electronic aspects of gastric electrical stimulation therapy, such as how the device generates and sends electrical signals to the stomach muscles.41,66,70\n\nEnterra refers to Enterra Therapy, a medical treatment designed to help control chronic nausea and vomiting associated with gastroparesis. This therapy works through what is known as gastric electrical stimulation (GES). Gastric electrical stimulation involves stimulating the smooth muscles in the lower abdomen with mild electrical pulses.70\n\nThe word gastrointestinal refers to the digestive system, which includes the stomach and intestines. Gastroparesis is a gastrointestinal disorder that affects the normal function of the stomach.66\n\nThe word disorders” refers to disorders or medical conditions that affect the normal function of the stomach and digestive tract. Gastroparesis is a gastrointestinal disorder that affects the normal function of the stomach.\n\nNeuromodulation is a technique used to regulate neural activity by stimulating or inhibiting nerve signals. In the context of gastroparesis, neuromodulation may be used to help control symptoms.41,66,70\n\nGastroparesis is a condition characterized by delayed gastric emptying and symptoms such as nausea, vomiting, early satiety, bloating, and upper abdominal pain.43,50,57\n\nPatients, This refers to individuals diagnosed with gastroparesis and undergoing treatment. Management of patients with gastroparesis involves a multidisciplinary approach that includes lifestyle changes, pharmacologic therapy, and, in some cases, surgical intervention.50\n\nGastroparesis often occurs in individuals with diabetes, and this condition is known as diabetic gastroparesis. Diabetes can cause damage to the vagus nerve, which controls muscle movement in digestion, causing gastroparesis.37\n\nGastric electrical stimulation is a procedure in which a small device that produces mild electrical pulses is implanted in the patient's body. This device helps promote the movement of food through the stomach more easily and controls symptoms associated with gastroparesis such as nausea and vomiting.66\n\n\nConclusion\n\nThe bibliometric topic study on gastroparesis focuses on identifying niche themes and discussing factors currently being studied. Key themes include interventions like diet modification, glucose control, and medication therapy with prokinetics and antiemetics. Cajal, or interstitial cajal, is crucial in coordinating smooth muscle concentration. Neighbors are common causes of gastroparesis, and transcutaneous stimulation, such as transcutaneous vagus stimulation, has been studied to develop more effective treatments. Prospective studies take time to analyze specific results. Motorcycle themes involve the vagus nerve, which controls muscle flow in medicine, and damage to it can cause gastroparesis. Emerging or declining themes include devices, electronics, and Enterra stimuli used in gastroparesis treatment. Basic themes include gastrointestinal disorders, neuromodulation, patients, diabetes, and gastric electrical stimulation. Gastroparesis, a condition affecting normal bowel function, is often associated with diabetes. Management involves multidisciplinary approaches, lifestyle changes, medication therapy, and bedtime interventions.\n\nVOSviewer software is an open-access tool that can be used as a cost-effective method for any scientometric analysis72\n\nAYS conducts research, gathers data, performs statistical analysis, and produces discussions and conclusions, RV and DAYS editing.",
"appendix": "Data availability statement\n\nFigshare: Transcutaneous stimulation as a niche theme in gastroparesis therapy\n\nDOI: https://doi.org/10.6084/m9.figshare.25991923.v1. 73\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nOpen Science Framework: PRISMA checklist & Flow Diagram: Transcutaneous stimulation as a niche theme in gastroparesis therapy\n\nDOI: https://doi.org/10.6084/m9.figshare.25991968.v1. 74\n\n\nReferences\n\nLi M, Gao N, Wang S, et al.: A global bibliometric and visualized analysis of the status and trends of gastroparesis research. Eur. J. Med. Res. 2023; 28(1): 543. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHuang IH, Schol J, Khatun R, et al.: Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. 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PubMed Abstract | Publisher Full Text\n\nFuglsang J, Ovesen PG: Pregnancy and delivery in a woman with type 1 diabetes, gastroparesis, and a gastric neurostimulator. Diabetes Care. 2015; 38(5): e75. PubMed Abstract | Publisher Full Text\n\nGottfried-Blackmore A, Adler EP, Fernandez-Becker N, et al.: Open-label pilot study: Non-invasive vagal nerve stimulation improves symptoms and gastric emptying in patients with idiopathic gastroparesis. Neurogastroenterol. Motil. 2020; 32(4): e13769. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGreenway F, Zheng J: Electrical stimulation as treatment for obesity and diabetes. J. Diabetes Sci. Technol. 2007; 1(2): 251–259. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHasler WL: Nausea, gastroparesis, and aerophagia. J. Clin. Gastroenterol. 2005; 39(5 Suppl 3): S223–S229. PubMed Abstract | Publisher Full Text\n\nHasler WL: Methods of gastric electrical stimulation and pacing: a review of their benefits and mechanisms of action in gastroparesis and obesity. Neurogastroenterol. Motil. 2009; 21(3): 229–243. PubMed Abstract | Publisher Full Text\n\nHendrickson JE, Hendrickson ET, Gehrie EA, et al.: Complex regional pain syndrome and dysautonomia in a 14-year-old girl responsive to therapeutic plasma exchange. J. Clin. Apher. 2016; 31(4): 368–374. PubMed Abstract | Publisher Full Text\n\nJiang Y, Soffer E: Electroceuticals for Neurogastroenterology and Motility Disorders. Curr. Gastroenterol. Rep. 2023; 25(4): 91–97. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhanna D, Melikterminas E: Gastrointestinal involvement in systemic sclerosis. Indian J. Rheumatol. 2008; 3(1): 13–20. Publisher Full Text\n\nLacy BE, Weiser K: Gastrointestinal motility disorders: an update. Digestive diseases (Basel, Switzerland). 2006; 24(3-4): 228–242. Publisher Full Text\n\nLee S, Abd-Elsayed A: Some Non-FDA Approved Uses for Neuromodulation in Treating Autonomic Nervous System Disorders: A Discussion of the Preliminary Support. Neuromodulation. 2016; 19(8): 791–803.\n\nLittmann L, Butschek R, Okeagu E: ECG Quiz. Rapid repetitive electric signals in a 12-lead ECG and in telemetry. J. Electrocardiol. 2013; 46(4): 366–367. PubMed Abstract | Publisher Full Text\n\nLoganathan P, Gajendran M, McCallum R: Current and future treatment management strategies for gastroparesis. Expert Opin. Orphan Drugs. 2019; 7(5): 211–221. Publisher Full Text\n\nMiller L, Farajidavar A, Vegesna A: Use of Bioelectronics in the Gastrointestinal Tract. Cold Spring Harb. Perspect. Med. 2019; 9(9). PubMed Abstract | Publisher Full Text | Free Full Text\n\nNavas CM, Patel NK, Lacy BE: Gastroparesis: Medical and Therapeutic Advances. Dig. Dis. Sci. 2017; 62(9): 2231–2240. Publisher Full Text\n\nOmer E, Kedar A, Nagarajarao HS, et al.: Cajal Cell Counts are Important Predictors of Outcomes in Drug Refractory Gastroparesis Patients With Neurostimulation. J. Clin. Gastroenterol. 2019; 53(5): 366–372. PubMed Abstract | Publisher Full Text\n\nPanda H, Mitchell P, Curley M, et al.: Prospective evaluation of gastric neurostimulation for diabetic gastroparesis in Canada. Can. J. Gastroenterol. Hepatol. 2015; 29(4): 198–202. PubMed Abstract | Publisher Full Text | Free Full Text\n\nParkman HP, Fass R, Foxx-Orenstein AE: Treatment of patients with diabetic gastroparesis. Gastroenterol. Hepatol. 2010; 6(6): 1–16.\n\nPasricha PJ, Pehlivanov ND, Gomez G, et al.: Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis. BMC Gastroenterol. 2008; 8: 21. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPaulon E, Nastou D, Jaboli F, et al.: Proof of concept: short-term non-invasive cervical vagus nerve stimulation in patients with drug-refractory gastroparesis. Frontline gastroenterology. 2017; 8(4): 325–330. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRahimiBashar F, Khoshraftar E, Tahmasebi R, et al.: Comparing the Effects of Acupuncture and Pharmacologic Therapies on Delayed Gastric Emptying: A Prospective, Block-Randomized, Single-Blinded, Parallel Clinical Trial. Iran Red Crescent Med J. 2016. Inpress.\n\nShanker A, Bashashati M, Rezaie A: Gastric Electrical Stimulation for Treatment of Refractory Gastroparesis: the Current Approach to Management. Curr. Gastroenterol. Rep. 2021; 23(2): 2. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSoares RV, Swanstrom LL: Endoscopic approaches to gastroparesis. Curr. Opin. Gastroenterol. 2015; 31(5): 368–373. Publisher Full Text\n\nSullivan A, Temperley L, Ruban A: Pathophysiology, Aetiology and Treatment of Gastroparesis. Dig. Dis. Sci. 2020; 65(6): 1615–1631. Publisher Full Text\n\nVanormelingen C, Tack J, Andrews CN: Diabetic gastroparesis. Br. Med. Bull. 2013; 105: 213–230. Publisher Full Text\n\nWagner J: The vagus nerve: current concepts in anaesthesia and ICU management. Southern African Journal of Anaesthesia and Analgesia. 2022; 28: 193–197. Publisher Full Text\n\nYe F, Liu Y, Li S, et al.: Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 2020; 318(3): G574–G581. PubMed Abstract | Publisher Full Text\n\nZheng T, Camilleri M: Management of Gastroparesis. Gastroenterol. Hepatol. 2021; 17(11): 515–525.\n\nZoll B, Jehangir A, Malik Z, et al.: Gastric Electric Stimulation for Refractory Gastroparesis. Journal of clinical outcomes management: JCOM. 2019; 26(1): 27–38. PubMed Abstract\n\nvan Eck NJ , Waltman L: Citation-based clustering of publications using CitNetExplorer and VOSviewer. Scientometrics. 2017; 111(2): 1053–1070.\n\nSaleh AY: Transcutaneous stimulation as a niche theme in gastroparesis therapy. figshare. 2024. Reference Source\n\nSaleh AY: PRISMA-ScR checklist & Flow Diagram: Transcutaneous stimulation as a niche theme in gastroparesis therapy. figshare. 2024. Reference Source"
}
|
[
{
"id": "311287",
"date": "29 Aug 2024",
"name": "Heithem Soliman",
"expertise": [
"Reviewer Expertise Gastric motility"
],
"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\nComment 1 : There are some issues in the English language that make some sentences difficult to understand. Comment 2 : The title refers to transcutaneous stimulation, thus, this treatment should be more highlighted in the results, and the authors should argue more why they focus mostly on this aspect. Comment 3 : Abstract: The introduction in the abstract is not correct. It does not define gastroparesis. Gastroparesis is defined by delayed gastric emptying, and is a motility disorder, but not by bile salt retention. Moreover, the epidemiological data are not precise, the prevalence of GPLS is not the same as the prevalence of gastroparesis, and the estimated prevalence of gastroparesis is lower to 1%. Comment 4 : The results in the abstract are not clear at all. It seems to be more likely the method of classifying articles, and not results. Moreover, the objective is also not correctly defined. Thus, the structure of the abstract should get less in methodological details, and give a better sum-up of the literature search of the authors, before moving to their conclusion. Introduction: Comment 4: GERD is an abbreviation that does not refer to gastric electrical stimulation, correct using GES. G-POEM is not a neurological technique, but an endoscopic mini-invasive surgical technique that aims to improve a potential pyloric obstruction. Comment 5 : The results seem to be merged with the Methods, which is a little bit confusing, and makes the article difficult to read. Moreover, many important articles assessing gastric electrical stimulation, which is a form of nerve stimulation are lacking (Ducrotte P, et al., 2020 [Ref-1]).\n\nAre the rationale for, and objectives of, the Systematic Review clearly stated? No\n\nAre sufficient details of the methods and analysis provided to allow replication by others? Yes\n\nIs the statistical analysis and its interpretation appropriate? 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.) Not applicable",
"responses": [
{
"c_id": "12334",
"date": "02 Sep 2024",
"name": "ARMAN YURISALDI SALEH",
"role": "Author Response",
"response": "Dear Reviewer Board Thank you for your feedback. We will make improvements in the future. This study uses the bibliometric methods which does not use statistical analysis in this study. Thank you in advance Best Regard Arman Yurisaldi Saleh"
},
{
"c_id": "12592",
"date": "22 Oct 2024",
"name": "ARMAN YURISALDI SALEH",
"role": "Author Response",
"response": "Transcutaneous Stimulation as a Niche Theme in Gastroparesis Therapy: A Bibliometric Analysis Revised Results: We discovered that transcutaneous stimulation holds great promise for treating gastroparesis. Patients' quality of life is enhanced and symptoms are reduced with this treatment. Thus, it is important to emphasize the need for more study and clinical application of transcutaneous stimulation. Abstract Revision Abstract: Introduction: A motility problem called gastroparesis is characterized by delayed stomach emptying. Between 0.9 and 1.3% of diabetic people are thought to have gastroparesis. Patient treatment may be enhanced by new diagnostic methods like osmotic pressure and gastric emptying. Methods: To find the most important subjects in the gastroparesis literature, we employed bibliometric analysis. Our attention was directed towards dietary adjustments, glucose regulation, and the function of transcutaneous stimulation in the treatment of gastroparesis. Results: According to our analysis, transcutaneous stimulation holds great promise for treating gastroparesis. We also found the necessity of multidisciplinary collaboration in the management of this illness. Conclusion: Further investigation into the topic of transcutaneous stimulation in the management of gastroparesis is warranted. Introduction Revision Introduction: Gastroesophageal reflux disease, or GERD for short, is not the same as gastric electrical stimulation, or GES for short. Furthermore, to treat a possible pyloric obstruction, a minimally invasive endoscopic surgical procedure called G-POEM (Gastric Per-Oral Endoscopic Myotomy) is used. Results and Methods Revision Methods: The primary subjects in the gastroparesis literature were determined by this study using bibliometric analysis. The techniques, findings, and primary themes presented in the publications determined their classification.\" Results: Our analysis's findings suggest that transcutaneous stimulation is a useful strategy for treating gastroparesis. This analysis also contained a significant paper that evaluated stomach electrical stimulation.\" Revision of Aims and Analysis Aims: This systematic review's objectives were to evaluate the body of research on transcutaneous stimulation and investigate its potential in the treatment of gastroparesis.\" Revision of Conclusions Conclusions: The results reported in the review corroborate our findings. Confirming the efficacy of transcutaneous stimulation in the treatment of gastroparesis requires additional research.\""
}
]
},
{
"id": "303094",
"date": "11 Oct 2024",
"name": "Hareesha Rishab Bharadwaj",
"expertise": [
"Reviewer Expertise Gastroenterology"
],
"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 the opportunity to peer review this manuscript. Whilst the topic has the potential to provide well-structured contribution to the field, with significant potential to influence future research in neuromodulation and gastroparesis treatments, I am afraid I do not believe that this manuscript does justice to the topic. 1. Although the title suggests that the paper refers to transcutaneous stimulation, the paper talks about a wide range of treatments for gastroparesis and does to focus on the above mentioned. 2. I believe that the general standard of writing is quite poor. There are a lot of inconsistencies in terminology. For instance, there are inconsistencies, such as the use of \"motorcycle themes\" (likely meant to be \"motor themes\"). Furthermore, I believe that the standard of writing could do with an improvement. 3. Grammar and Flow: In a few instances, sentence structure could be improved for clarity. For example, \"Neighbors are common causes of gastroparesis\" is ambiguous and could be better phrased. 4. There are some structural flaws to the paper. The abstract mentions gastroparesis as a condition which is caused by the accumulation of bile salts which is not the case. However, in the text, the correct definition of gastroparesis has been mentioned. The abstract does not summaries the results of the paper consistently, but there has been an overt mention of the methods of the paper. You should talk more about what results you have obtained in the abstract to give a succinct overview of the topic. The epidemiology data is not correct. For instance, the authors have equated the prevalence of ‘gastroparesis like symptoms’ to gastroparesis, which is not the same. Furthermore, the authors have mentioned G-POEM as a neurological technique, which is not correct. 5. I have noted some inconsistencies in abbreviations. GERD is not the abbreviation for gastric stimulation but is for gastroesophageal reflux disease in the American standard of English. 6. There are however, some positives to the paper. If the paper is revised to describing the niche themes of gastroparesis, then the authors have done well to explain some of them. I liked the usage of VOS viewer for network visualisation of themes. I believe the paper could use a section on the projection of the themes analysed to the future. Overall, I thank the authors for the opportunity to peer review, and I apologies for the unfavorable decision. Good luck with your future endeavors.\nRegards, Hareesha Rishab Bharadwaj\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? I cannot comment. A qualified statistician is required.\n\nAre the conclusions drawn adequately supported by the results presented in the review? Partly\n\nIf this is a Living Systematic Review, is the ‘living’ method appropriate and is the search schedule clearly defined and justified? (‘Living Systematic Review’ or a variation of this term should be included in the title.) Not applicable",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-658
|
https://f1000research.com/articles/13-285/v1
|
17 Apr 24
|
{
"type": "Brief Report",
"title": "The retrieval of neutral and positive autobiographical memories: a pilot study",
"authors": [
"Xinning Su",
"Akira Midorikawa"
],
"abstract": "Background Several studies have shown that the retrieval of positive memories may play a role in emotional regulation. However, it is unclear whether the effects of neutral and positive autobiographical memories differ. There is a need to confirm that genuinely neutral autobiographical memories can be retrieved without bias in response to a prompt to recall neutral memories.\n\nMethods In this pilot study, using “home” and “study” as cue words, we investigated whether participants were able to retrieve appropriate autobiographical memories when asked to recall a limited number of neutral or positive memories.\n\nResults Although participants were asked to recall neutral autobiographical memories, they tended to recall positive memories.\n\nConclusions Our results support the concept of positive memory bias and suggest that future work should consider combining neutral and positive autobiographical memories, namely by asking participants to recall neutral–positive memories.",
"keywords": [
"autobiographical memories",
"emotional valence",
"positive memory bias",
"neutral–positive memories"
],
"content": "Introduction\n\nAutobiographical memory is defined as memory for information relating to the self (Brewer, 1986). It is believed to play a role in shaping an individual’s self-awareness and identity over time (Conway, 2005; Conway & Pleydell-Pearce, 2000; Tulving, 2002). Autobiographical memory is strongly linked to emotion (Holland & Kensinger, 2010). Several studies have shown that individuals with emotional disorders, such as depression (King et al., 2010) and anxiety (Krans et al., 2014), exhibit autobiographical memory biases; for example, they exhibit more negative autobiographical memories compared with control participants.\n\nAlthough individuals may repeatedly recall past negative experiences to learn from their mistakes, repeated recall of negative events constitutes rumination, a maladaptive cognitive process that is strongly associated with the onset and perpetuation of depression (Nolen-Hoeksema & Morrow, 1991; Nolen-Hoeksema et al., 2008). Harris et al. (2010) found that repeated retrieval of positive autobiographical memories inhibited the recall of negative autobiographical memories associated with the same cue word. Additionally, Burton and King (2004, 2009) found that writing about positive experiences increased positive affect. These results suggest that the retrieval of positive memories can facilitate emotional regulation.\n\nIn addition to autobiographical memories with positive or negative valence, memories can be neutral (D’Argembeau et al., 2003). It is unclear whether neutral and positive autobiographical memories contribute in a similar manner to emotion regulation. However, before that question can be answered, there is a need to determine whether genuinely neutral autobiographical memories can be retrieved without bias in response to a prompt to recall neutral memories. Several studies have shown that when participants are asked to recall as many autobiographical memories as possible, they generally recall more positive autobiographical events than neutral and negative events (Berntsen, 1996; Clark et al., 2013; Marsh et al., 2019). This phenomenon is known as positive memory bias (Adler & Pansky, 2020; Skowronski, 2011; Walker et al., 2003). However, most previous studies did not limit the number of recalls, which varied among events according to emotional valence. Notably, it is unclear whether participants can recall genuinely neutral memories when prompted if the number of recalls is limited.\n\nTherefore, in this pilot study, we adopted the cue words used by Harris et al. (2010), namely “home” and “study”, to investigate whether appropriate autobiographical memories can be retrieved by participants who are asked to recall a limited number of neutral or positive memories.\n\n\nMethods\n\nIn total, 10 students (five men and five women) participated in this study (mean age = 21.90 years; range: 19–24 years). All participants were enrolled in a preparatory school in Tokyo, Japan, and recruited in a classroom setting.\n\nThe experiment had a 2 × 2 mixed design. The between-subjects factor was valence (positive/neutral), and the within-subjects factor was cue (home/study).\n\nThis study was conducted in line with the Declaration of Helsinki. It was approved by the ethics committee of Chuo University, on 4 August 2020, vide approval number 2020-02. Written informed consent was obtained from all individual participants included in the study.\n\nParticipants were divided into positive and neutral groups. The two cue words, home and study, were presented to each group. Participants were asked to generate five positive or five neutral autobiographical memories for each cue. Researchers informed the participants that the “study events” were associated with study or work, whereas the “home events” were associated with home or family.\n\nAfter the retrieval of autobiographical memories for each cue word, participants briefly reported the context of the recalled events in a verbal manner, and a researcher recorded the description. After they had reported events, participants were asked to rate the valence of those events (1 = Very negative, 7 = Very positive).\n\n\nResults\n\nOn a 7-point Likert response scale, the neutral score (i.e., 4) was regarded as the baseline; differences between self-rated scores for the four memory types (i.e., home memories in the positive group, study memories in the positive group, home memories in the neutral group, and study memories in the neutral group) and the neutral score were calculated. One-sample t-tests were used to determine whether differences between the scores for each memory type and the neutral score were significant. We found significant differences between scores for all memory types and the neutral score (home memory in the positive group, t(4) = 5.06, p < 0.01, d = 2.26; study memory in the positive group, t(4) = 3.50, p = 0.03, d = 1.57; home memory in the neutral group, t(4) = 3.92, p = 0.02, d = 1.75; and study memory in the neutral group, t(4) = 7.20, p < 0.01, d = 3.22) (Figure 1a).\n\nDashed line in (a) is the neutral score (baseline), and error bars in (b) represent standard error.\n\nAs shown in Figure 1b, a 2 (valence group: positive/neutral) × 2 (cue: home/study) mixed ANOVA for event valence was conducted. There was no main effect of valence group (F(1,8) = 3.30, p = 0.11, ηp2 = 0.29), no main effect of cue (F(1,8) = 2.27, p = 0.17, ηp2 = 0.22), and no interaction effect (F(1,8) = 3.35, p = 0.10, ηp2 = 0.30).\n\n\nDiscussion\n\nIn this study, we used the cue words home and study to determine whether appropriate autobiographical memories could be retrieved by participants who were asked to recall neutral or positive memories. We found a bias toward recalling positive events in both the neutral and positive groups, although participants were asked to recall neutral events. Moreover, there were no significant differences in memory ratings between the two groups.\n\nOne explanation for the above results is positive memory bias (Adler & Pansky, 2020; Skowronski, 2011; Walker et al., 2003). Several studies have shown that more positive autobiographical events are generally recalled, whether voluntarily or involuntarily, compared with neutral or negative events (Berntsen, 1996; Clark et al., 2013; Marsh et al., 2019). However, unlike previous studies, we limited the number of recalled memories, asking participants to generate five positive or five neutral autobiographical memories for each cue. Thus, the neutral and positive groups did not differ according to the number of recalls; nevertheless, they showed emotional valence bias. The self-memory system, in which autobiographical memory retrieval is influenced by current beliefs, active goals, and self-image, supports positive memory bias (Conway, 2005). People generally retrieve autobiographical memories consistent with their self-image and beliefs, which tend to be positive.\n\nIn conclusion, although participants in the present study were asked to recall neutral autobiographical memories, they tended to recall positive events. Future work should consider combining neutral and positive autobiographical memories, namely by asking participants to recall neutral–positive memories. We anticipate more studies investigating whether, similar to the effects of retrieving positive memories (Burton & King, 2004; Burton & King, 2009; Harris et al., 2010), the retrieval of neutral–positive memories also inhibits the recall of negative memories or increases positive emotions. Such studies may inform strategies for emotional regulation.\n\nThis study was conducted in line with the Declaration of Helsinki. It was approved by the Ethics Committee of Chuo University, on 4 August 2020, vide approval number 2020-02. Written informed consent was obtained from all individual participants included in the study.",
"appendix": "Data availability statement\n\nThis study contains the following underlying data:\n\nFighsare, Data for “the retrieval of neutral and positive autobiographical memories: a pilot study” https://doi.org/10.6084/m9.figshare.24939264.v1 (Su et al., 2024).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAdler O, Pansky A: A “rosy view” of the past: Positive memory biases. Cognitive biases in health and psychiatric disorders: Neurophysiological foundations. Elsevier Academic Press; 2020; pp. 139–171. Publisher Full Text\n\nBerntsen D: Involuntary autobiographical memories. Appl. Cogn. Psychol. 1996; 10(5): 435–454. Publisher Full Text\n\nBrewer WF: What is autobiographical memory? Autobiographical memory. Cambridge University Press; 1986; pp. 25–49. Publisher Full Text\n\nBurton CM, King LA: The health benefits of writing about intensely positive experiences. J. Res. Pers. 2004; 38(2): 150–163. Publisher Full Text\n\nBurton CM, King LA: The health benefits of writing about positive experiences: the role of broadened cognition. Psychol. Health. 2009; 24(8): 867–879. PubMed Abstract | Publisher Full Text\n\nClark IA, Mackay CE, Holmes EA: Positive involuntary autobiographical memories: you first have to live them. Conscious. Cogn. 2013; 22(2): 402–406. PubMed Abstract | Publisher Full Text | Free Full Text\n\nConway MA: Memory and the self. J. Mem. Lang. 2005; 53(4): 594–628. Publisher Full Text\n\nConway MA, Pleydell-Pearce CW: The construction of autobiographical memories in the self-memory system. Psychol. Rev. 2000; 107(2): 261–288. PubMed Abstract | Publisher Full Text\n\nD’Argembeau A, Comblain C, Van der Linden M: Phenomenal characteristics of autobiographical memories for positive, negative, and neutral events. Appl. Cogn. Psychol. 2003; 17(3): 281–294. Publisher Full Text\n\nHarris CB, Sharman SJ, Barnier AJ, et al.: Mood and retrieval-induced forgetting of positive and negative autobiographical memories. Appl. Cogn. Psychol. 2010; 24(3): 399–413. Publisher Full Text\n\nHolland AC, Kensinger EA: Emotion and autobiographical memory. Phys. Life Rev. 2010; 7(1): 88–131. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKing MJ, MacDougall AG, Ferris SM, et al.: A review of factors that moderate autobiographical memory performance in patients with major depressive disorder. J. Clin. Exp. Neuropsychol. 2010; 32(10): 1122–1144. PubMed Abstract | Publisher Full Text\n\nKrans J, de Bree J , Bryant RA: Autobiographical memory bias in social anxiety. Memory. 2014; 22(8): 890–897. Publisher Full Text\n\nMarsh L, Edginton T, Conway MA, et al.: Positivity bias in past and future episodic thinking: Relationship with anxiety, depression, and retrieval-induced forgetting. Q. J. Exp. Psychol. 2019; 72(3): 508–522. PubMed Abstract | Publisher Full Text\n\nNolen-Hoeksema S, Morrow J: A prospective study of depression and posttraumatic stress symptoms after a natural disaster: The 1989 Loma Prieta earthquake. J. Pers. Soc. Psychol. 1991; 61(1): 115–121. PubMed Abstract | Publisher Full Text\n\nNolen-Hoeksema S, Wisco BE, Lyubomirsky S: Rethinking Rumination. Perspect. Psychol. Sci. 2008; 3(5): 400–424. PubMed Abstract | Publisher Full Text\n\nSkowronski JJ: The positivity bias and the fading affect bias in autobiographical memory: A self-motives perspective. Handbook of self-enhancement and self-protection. The Guilford Press; 2011; pp. 211–231.\n\nSu X: The retrieval of neutral and positive autobiographical memories: a pilot study.figshare.2024. Publisher Full Text\n\nTulving E: Chronesthesia: Conscious awareness of subjective time. Principles of frontal lobe function. Oxford University Press; 2002; pp. 311–325. Publisher Full Text\n\nWalker WR, Skowronski JJ, Thompson CP: Life is Pleasant—and Memory Helps to Keep it that Way! Rev. Gen. Psychol. 2003; 7(2): 203–210. Publisher Full Text"
}
|
[
{
"id": "294508",
"date": "16 Jul 2024",
"name": "Arkadiy Maksimovskiy",
"expertise": [
"Reviewer Expertise Cognitive neuroscience and memory 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\nThis pilot study tackled an important question by investigating whether participants were able to retrieve appropriate autobiographical memories when asked to recall a limited number of neutral or positive memories. The study found that although participants were asked to recall neutral memories, they tended to recall positive memories. This is intended to support the concept of positive memory bias. However, several limitations need to be addressed before the intended conclusion can be reached.\n1. The word ‘study’ was not used in the original procedure outlined by Harris (2010). Please explain why it was selected. Additionally, the terms ‘study’ and ‘home’ might overlap in our day and age. Please further explain the distinction.\n\n2. “In addition to autobiographical memories with positive or negative valence, memories can be neutral (D’Argembeau et al., 2003). It is unclear whether neutral and positive autobiographical memories contribute similarly to emotion regulation. However, before that question can be answered…”\nPlease explain why neutral memories might contribute in the same way as positive memories. Why is this an important question? What are the mechanisms behind it?\n3. “However, most previous studies did not limit the number of recalls, which varied among events according to emotional valence. Notably, it is unclear whether participants can recall genuinely neutral memories when prompted if the number of recalls is limited.”\nIt is unclear how neutral memory might be linked to the number of recalls.\n4. Figure 1: Why are two plots (box and whisker as well as bar graph) used to illustrate the same concept?\nFigure 1a: Please provide a distribution of scores for each participant. From the figure, it appears that ‘Positive study’ did not significantly differ from the neutral condition (contrary to the description), and the other positive category (i.e., ‘positive home’) barely (if at all) differed from neutral conditions. Please provide a distribution of individual scores and explain.\n5. If you’re asking participants to recall neutral events, but they recalled positive events, there is the possibility that participants did not see their ratings as neutral, which means the manipulation did not work (rather than a bias provided by authors). Please provide an explanation and further evidence as to how this is interpreted as a positive memory bias and whether any manipulation checks were done to ensure that neutral memories could be recalled.\n\n6. Thank you for providing original data. I ran a quick one-tailed t-test and am not seeing differences between the conditions (T-statistic: 1.82; P-value: 0.11). The code in python is below – please explain why this insignificant finding is consistent with your provided interpretation of the data:\n# Filter data for positive and neutral groups positive_data = data[data['group'] == 'positive']['valence_mean'] neutral_data = data[data['group'] == 'neutral']['valence_mean'] # Perform a t-test t_stat, p_value_two_tailed = stats.ttest_ind(positive_data, neutral_data) # Adjust the p-value for a one-sided test p_value_one_tailed = p_value_two_tailed / 2 if t_stat > 0 else 1 - p_value_two_tailed / 2 # Display the results print(f'T-statistic: {t_stat}') print(f'P-value: {p_value}')\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? No\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": "12644",
"date": "22 Oct 2024",
"name": "Xinning Su",
"role": "Author Response",
"response": "Respons to Dr. Arkadiy Maksimovskiy: We would like to express our sincere gratitude to the reviewers for your insightful comments on our manuscript. Your valuable comments have significantly contributed to enhancing the quality of our work. Comment 1: The word ‘study’ was not used in the original procedure outlined by Harris (2010). Please explain why it was selected. Additionally, the terms ‘study’ and ‘home’ might overlap in our day and age. Please further explain the distinction. Response: Thank you for this pertinent feedback. The cue words used by Harris et al. (2010) were ‘home’ and ‘work’, which may have been due to the wide age range of their participants (17–42 years). For the cue word ‘work’, Harris et al. (2010) asked participants to recall autobiographical memories related to study or work. Given that our participants were similarly aged college students (19–24 years), the cue words in our experiment were ‘home’ and ‘study.’ The researcher told participants that the ‘study events’ should be related to study or work, and the ‘home events’ should be related to home or family. Therefore, we believe that although the words presented on the computer screen differed, in combination with the verbal instructions, we used the same cue words as Harris et al., (2010). For this reason, we have added the following description to the Introduction (The last paragraph of the Introduction, lines 3-6) Since our ultimate aim is to extend the findings of Harris et al. (2010), in the present pilot study, we adopted the same cue words as Harris et al. (2010), namely “home” and “study”, to investigate…… In addition, we added the following description to the Procedure. (Paragraph 1 of the Procedure, lines 1-9) The cue words used by Harris et al. (2010) were “home” and “work”, likely chosen due to the wide age range of their participants (17–42 years old). For the cue word “work”, Harris et al. (2010) asked participants to recall autobiographical memories related to study or work. Given that all of our participants were college students of similar age, the cue words in our experiment were “home” and “study”, presented to each group. Participants were asked to generate five positive or five neutral autobiographical memories for each cue. Researchers informed the participants that the “study events” should be associated with study or work, whereas the “home events” should be related to home or family. Comment 2: “In addition to autobiographical memories with positive or negative valence, memories can be neutral (D’Argembeau et al., 2003). It is unclear whether neutral and positive autobiographical memories contribute similarly to emotion regulation. However, before that question can be answered…” Please explain why neutral memories might contribute in the same way as positive memories. Why is this an important question? What are the mechanisms behind it? Response: Thank you for this insightful feedback. We appreciate the opportunity to clarify these important points. To address the first question: Why might neutral memories contribute in the same way as positive memories? We have added the following explanation in the revised manuscript. (Paragraph 2 of the Introduction, lines 5-8) Regarding whether neutral memory retrieval can also inhibit the forgetting of negative memories, evidence from recent studies on semantic memory indicates that retrieving neutral semantic memories can lead to forgetting related negative memories (Greer et al., 2024). To address the second question: Why is this an important question? We have added the following explanation. (Paragraph 2 of the Introduction, lines 11-16) ……it is worth investigating whether the effects observed with neutral semantic memories might also apply to neutral autobiographical memories. Should neutral autobiographical memories function similarly to positive ones, this could extend the findings of Harris et al. (2010), offer new insights into the mechanisms of memory and emotion, and suggest alternative strategies for mitigating the effects of negative memories. To address the third issue: What are the mechanisms behind it? As well as link semantic and autobiographical memories. We have added the following clarification. (Paragraph 2 of the Introduction, lines 8-16) Considering that autobiographical and semantic memories share overlapping neural bases (Graham et al., 2003), and negative autobiographical memories are more strongly associated with emotional disorders (King et al., 2010; Krans et al., 2014), it is worth investigating whether the effects observed with neutral semantic memories might also apply to neutral autobiographical memories. Should neutral autobiographical memories function similarly to positive ones, this could extend the findings of Harris et al. (2010), offer new insights into the mechanisms of memory and emotion, and suggest alternative strategies for mitigating the effects of negative memories. Comment 3: “However, most previous studies did not limit the number of recalls, which varied among events according to emotional valence. Notably, it is unclear whether participants can recall genuinely neutral memories when prompted if the number of recalls is limited.” It is unclear how neutral memory might be linked to the number of recalls. Response: Thank you for this pertinent feedback. Since our ultimate aim is to extend the findings of Harris et al. (2010), the pilot study conducted before this (i.e., the current study) needed to consider Harris’s procedures. Therefore, we limited the number of recalls and emotional valence. To clarify this issue, we added the following explanation. However, before we extend the findings of Harris et al. (2010), a pilot study is necessary to determine whether genuinely neutral autobiographical memories can be retrieved without bias when prompted to recall neutral memories.…… (Paragraph 3 of the Introduction, lines 1-3) However, most previous studies did not limit the number or valence of recalls. According to the procedure of Harris et al. (2010), participants were explicitly asked to recall a limited number of specified emotional events associated with each cue word. Since our ultimate aim is to extend the findings of Harris et al. (2010), in the present pilot study, we adopted the same cue words as Harris et al. (2010), namely “home” and “study”, to investigate whether appropriate autobiographical memories when asked to recall a limited number of neutral or positive memories. (Paragraph 4 of the Introduction) Comment 4: Figure 1: Why are two plots (box and whisker as well as bar graph) used to illustrate the same concept? Figure 1a: Please provide a distribution of scores for each participant. From the figure, it appears that ‘Positive study’ did not significantly differ from the neutral condition (contrary to the description), and the other positive category (i.e., ‘positive home’) barely (if at all) differed from neutral conditions. Please provide a distribution of individual scores and explain. Response: Thank you for this insightful feedback. Based on your advice, we removed the bar graph, kept only the box-and-whisker plot and added the distribution of individual scores. (Figure 1) Comment 5: If you’re asking participants to recall neutral events, but they recalled positive events, there is the possibility that participants did not see their ratings as neutral, which means the manipulation did not work (rather than a bias provided by authors). Please provide an explanation and further evidence as to how this is interpreted as a positive memory bias and whether any manipulation checks were done to ensure that neutral memories could be recalled. Response: Thank you for raising this important point. As we followed Harris et al.’s (2010) methodology for the present study, we used self-rating valence and did not conduct explicit manipulation checks to confirm whether participants recalled neutral events as instructed. To make this clearer, we revised the Procedure as follows: (Paragraph 2 of the Procedure, lines 3-5) Then, as in Harris et al.’s (2010) methodology, after they had reported events, participants were asked to rate the valence of those events (1 = Very negative, 7 = Very positive). However, as you point out, this is a limitation of the current study. we have therefore added the following clarification to the Discussion section. (Paragraph 3 of the Discussion, lines 5-11) This study had some limitations. ……Second, we adopted self-rating valence as per the methodology of Harris et al. (2010). However, self-ratings may be biased by various factors, including participants’ subjective interpretation of what constitutes a neutral event and their current mood (Chiorri & Vannucci, 2024). Given the potential for subjective bias, future studies should incorporate both subjective self-ratings and objective assessments by independent raters to ensure a more accurate categorization of recalled events. This will allow for better verification of whether neutral memories are indeed perceived as neutral or if a bias toward positivity has occurred. Comment 6: Thank you for providing original data. I ran a quick one-tailed t-test and am not seeing differences between the conditions (T-statistic: 1.82; P-value: 0.11). The code in python is below – please explain why this insignificant finding is consistent with your provided interpretation of the data: # Filter data for positive and neutral groups positive_data = data[data['group'] == 'positive']['valence_mean'] neutral_data = data[data['group'] == 'neutral']['valence_mean'] # Perform a t-test t_stat, p_value_two_tailed = stats.ttest_ind(positive_data, neutral_data) # Adjust the p-value for a one-sided test p_value_one_tailed = p_value_two_tailed / 2 if t_stat > 0 else 1 - p_value_two_tailed / 2 # Display the results print(f'T-statistic: {t_stat}') print(f'P-value: {p_value}') Response: Thank you for confirming our data and running the t-test. This t-test analysed whether there was a difference in self-reported valence ratings between the different valence groups (positive or neutral). The result was that there was no significant difference. This result is consistent with the ANOVA results we provided in the article. We conducted a 2 (valence group: positive/neutral) × 2 (cue: home/study) mixed ANOVA on self-reported valence ratings. The results revealed a nonsignificant main effect of the valence group. Therefore, thank you for validating our results. Although the result is negative (nonsignificant), it is still valuable to report for its potential contribution to understanding the topic. Once again, we sincerely thank you for your helpful comments and look forward to further comments on our manuscript."
}
]
},
{
"id": "298790",
"date": "29 Jul 2024",
"name": "Xinxu Shen",
"expertise": [
"Reviewer Expertise episodic memory",
"decision making"
],
"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 pilot study by Xinning Su and Akira Midorikawa explores whether participants can retrieve genuinely neutral autobiographical memories using the cue words \"home\" and \"study.\" Despite being asked to recall neutral memories, participants showed a positive memory bias, often recalling positive events instead. This study addressed an important question, but I have some concerns about the motivation behind the study and the methods. see below:\nThe authors discuss how the repeated retrieval of positive autobiographical memories could potentially inhibit the recall of negative autobiographical memories. However, before delving into the specifics of their study and the underlying motivations (particularly the question of whether neutral and positive autobiographical memories contribute similarly to emotion regulation), it would be beneficial to examine prior research on the impact of retrieving neutral autobiographical memories. Specifically, it's essential to investigate whether the retrieval of neutral autobiographical memories can also inhibit the recall of negative memories. The authors should provide a clear rationale for the selection of specific cue words used in their study. This includes explaining why these particular words were chosen and how they align with the study's objectives. Additionally, it would be beneficial to consider incorporating a broader range of neutral cue words. This diversity could ensure a more comprehensive examination of the effects of neutral memory retrieval on the inhibition of negative memories and provide a more robust dataset for analysis.\n\nThe use of self-rated valence to score autobiographical memories can introduce bias, as individuals may perceive and rate their memories subjectively. To mitigate this issue, it would be advantageous to have an independent rater evaluate the memories. This approach could provide a more objective assessment of the valence of memories, reducing the potential for self-report biases and enhancing the reliability of the study's findings.\n\nThe statement \"People generally retrieve autobiographical memories consistent with their self-image and beliefs, which tend to be positive\" appears abruptly without prior mention of self-image or beliefs. It is crucial to introduce and discuss the concept of self-image and beliefs earlier in the manuscript. Providing a theoretical framework or citing relevant literature on how self-image and beliefs influence memory retrieval could offer context and support for this assertion. This would help integrate the statement more seamlessly into the discussion and strengthen the argument.\n\nThe conclusion suggesting that future research should consider combining neutral and positive autobiographical memories by asking participants to recall neutral–positive memories is not well-supported by the current study. There is insufficient evidence to indicate that neutral and positive autobiographical memories function similarly, despite the observation that individuals tend to recall neutral memories more positively. To substantiate this conclusion, the authors should present stronger empirical evidence or theoretical justification demonstrating the potential benefits and similarities of combining these types of memories in emotion regulation and memory inhibition 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? 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? Partly",
"responses": [
{
"c_id": "12645",
"date": "22 Oct 2024",
"name": "Xinning Su",
"role": "Author Response",
"response": "Response to Dr. Xinxu Shen: We would like to express our sincere gratitude to the reviewers for your insightful comments on our manuscript. Your valuable comments have significantly contributed to enhancing the quality of our work. Comment 1: The authors discuss how the repeated retrieval of positive autobiographical memories could potentially inhibit the recall of negative autobiographical memories. However, before delving into the specifics of their study and the underlying motivations (particularly the question of whether neutral and positive autobiographical memories contribute similarly to emotion regulation), it would be beneficial to examine prior research on the impact of retrieving neutral autobiographical memories. Specifically, it's essential to investigate whether the retrieval of neutral autobiographical memories can also inhibit the recall of negative memories. Response: Thank you for this insightful comment. Previous research involving expressive writing has indeed explored the use of neutral content. For example, Sheerin et al. (2018) asked participants to write about neutral events, such as “what you did today”, and found that neutral writing also contributed to emotion regulation. However, due to paradigm differences, we did not include these studies in our current discussion. As for whether the retrieval of neutral autobiographical memories can inhibit the recall of negative memories, to our knowledge, no studies have specifically investigated this. However, a recent study found that retrieving neutral semantic memories can inhibit the recall of negative memories. We have added the following description to address this point (Paragraph 2 of the Introduction, lines 5-16): Regarding whether neutral memory retrieval can also inhibit the recall of negative memories, evidence from recent studies on semantic memory indicates that retrieving neutral semantic memories can lead to forgetting related negative memories (Greer et al., 2024). Considering that autobiographical and semantic memories share overlapping neural bases (Graham et al., 2003), and negative autobiographical memories are more strongly associated with emotional disorders (King et al., 2010; Krans et al., 2014), it is worth investigating whether the effects observed with neutral semantic memories might also apply to neutral autobiographical memories. Should neutral autobiographical memories function similarly to positive ones, this could extend the findings of Harris et al. (2010), offer new insights into the mechanisms of memory and emotion, and suggest alternative strategies for mitigating the effects of negative memories. Comment 2: The authors should provide a clear rationale for the selection of specific cue words used in their study. This includes explaining why these particular words were chosen and how they align with the study's objectives. Additionally, it would be beneficial to consider incorporating a broader range of neutral cue words. This diversity could ensure a more comprehensive examination of the effects of neutral memory retrieval on the inhibition of negative memories and provide a more robust dataset for analysis. Response: Thank you for this pertinent feedback. We have added the following explanation to clarify why these particular words were chosen. (Paragraph 1 of the Procedure, lines 1-9) The cue words used by Harris et al. (2010) were “home” and “work”, likely chosen due to the wide age range of their participants (17–42 years old). For the cue word “work”, Harris et al. (2010) asked participants to recall autobiographical memories related to study or work. Given that all of our participants were college students of similar age, the cue words in our experiment were “home” and “study”, presented to each group. Participants were asked to generate five positive or five neutral autobiographical memories for each cue. Researchers informed the participants that the “study events” should be associated with study or work, whereas the “home events” should be related to home or family. In addition, we have included your advice in the Discussion section of the revised version of the article. (Paragraph 3 of the Discussion, lines 1-5) This study had some limitations. First, since our ultimate aim is to extend the findings of Harris et al. (2010), the methods and cue words employed in this pilot study align with those described by Harris et al. (2010). While this approach is appropriate for the present study’s purposes, it would be beneficial to incorporate more neutral cue words to broaden the results further. Comment 3: The use of self-rated valence to score autobiographical memories can introduce bias, as individuals may perceive and rate their memories subjectively. To mitigate this issue, it would be advantageous to have an independent rater evaluate the memories. This approach could provide a more objective assessment of the valence of memories, reducing the potential for self-report biases and enhancing the reliability of the study's findings. Response: Thank you for this insightful feedback. As you rightly pointed out, having an independent rater evaluate the memories is essential. Therefore, to address this limitation, we have added the following statement to the Discussion section. (Paragraph 3 of the Discussion, lines 5-11) This study had some limitations. ……Second, we adopted self-rating valence as per the methodology of Harris et al. (2010). However, self-ratings may be biased by various factors, including participants’ subjective interpretation of what constitutes a neutral event and their current mood ( Chiorri & Vannucci, 2024). Given the potential for subjective bias, future studies should incorporate both subjective self-ratings and objective assessments by independent raters to ensure a more accurate categorization of recalled events. This will allow for better verification of whether neutral memories are indeed perceived as neutral or if a bias toward positivity has occurred. Comment 4: The statement \"People generally retrieve autobiographical memories consistent with their self-image and beliefs, which tend to be positive\" appears abruptly without prior mention of self-image or beliefs. It is crucial to introduce and discuss the concept of self-image and beliefs earlier in the manuscript. Providing a theoretical framework or citing relevant literature on how self-image and beliefs influence memory retrieval could offer context and support for this assertion. This would help integrate the statement more seamlessly into the discussion and strengthen the argument. Response: Thank you for your valuable feedback. In response to your suggestion, we have added the following note to the Introduction. (Paragraph 3 of the Introduction, lines 10-13) The self-memory system (Conway, 2005) suggests that autobiographical memory retrieval is influenced by an individual’s current beliefs, active goals, and self-image, which tend to be positive. As a result, people may unconsciously gravitate toward recalling positive autobiographical memories. Comment 5: The conclusion suggesting that future research should consider combining neutral and positive autobiographical memories by asking participants to recall neutral–positive memories is not well-supported by the current study. There is insufficient evidence to indicate that neutral and positive autobiographical memories function similarly, despite the observation that individuals tend to recall neutral memories more positively. To substantiate this conclusion, the authors should present stronger empirical evidence or theoretical justification demonstrating the potential benefits and similarities of combining these types of memories in emotion regulation and memory inhibition studies. Response: Thank you for your insightful feedback. In response to your suggestion, we have added the following note to the Discussion. (The last paragraph of the Discussion) In conclusion, despite some limitations, we found that when limiting the number of recalls, participants tended to recall positive events even when asked to recall neutral autobiographical memories. Previous studies have found that retrieval of neutral semantic memories leads to forgetting of negative semantic memories (Greer et al., 2024), while retrieval of positive autobiographical memories leads to forgetting of negative autobiographical memories (Harris et al., 2010). Therefore, it is necessary to extend the findings of Harris et al. (2010) to examine whether neutral autobiographical memories can also inhibit the recall of negative memories. However, before extending the findings of Harris et al. (2010), we conducted this pilot study to determine whether genuinely neutral autobiographical memories can be retrieved without bias when prompted to recall neutral memories. Based on the results of this pilot study, it will be necessary to continue refining our understanding. Additionally, we can propose innovative ideas, such as exploring whether future work could integrate neutral and positive autobiographical memories, by asking participants to recall neutral–positive memories. We look forward to further research investigating whether, similar to the effects of retrieving positive memories (Burton & King, 2004; Burton & King, 2009; Harris et al., 2010), retrieving neutral–positive memories may also inhibit the recall of negative memories or enhance positive emotions. Such studies could provide valuable insights for developing emotional regulation strategies. Once again, we sincerely thank you for your helpful comments and look forward to further comments on our manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/13-285
|
https://f1000research.com/articles/13-622/v1
|
11 Jun 24
|
{
"type": "Research Article",
"title": "Paradoxical Leadership and Employee Proactive Work Behavior: Exploring the Mediating Role of Perceived Psychological Contract Fulfillment.",
"authors": [
"Ibrahim Elshaer",
"Alaa M. S. Azazz",
"Tamer Ahmed Abdulaziz",
"Sameh Fayyad",
"Alaa M. S. Azazz",
"Tamer Ahmed Abdulaziz",
"Sameh Fayyad"
],
"abstract": "Background This study delves into the intricate interplay among paradoxical leadership (PL), employees’ proactive work behaviour (EPWB), and perceived psychological contract fulfilment (PPCF). PL, characterized by its simultaneous emphasis on apparently contradictory behaviours, has garnered attention due to its potential to foster innovation, adaptability, and creativity. The study’s main objective is to thoroughly explore the complexities of PL, its influence on EPWB, and whether the PPCF serves as a mediator.\n\nMethods A survey was distributed to 338 hotel and travel agency employees to gather data. The data was analysed using structural equation modelling through a SmartPLS program.\n\nResults The results reveal a positive correlation between PL and EPWB. Additionally, PPCF partially mediates this relationship, indicating its vital role in exploring the positive impact of PL on boosting proactive behaviours.\n\nConclusions This research brings forth meaningful contributions to both theoretical and practical dimensions. Theoretically, it enhances our comprehension of how PL manifests in the distinctive landscape of the hospitality and tourism domain, substantiating its potential to drive proactive behaviours among employees. The mediation of PPCF enriches our grasp of the underlying mechanisms, accentuating the significance of maintaining harmonized and consistent leadership practices. From a practical vantage point, these findings offer valuable insights for hospitality and tourism establishments aspiring to optimize their leadership strategies for cultivating proactive work behaviour among their workforces.",
"keywords": [
"Paradoxical leadership",
"proactive behavior",
"hotel industry",
"tourism industry",
"psychological contract."
],
"content": "1. Introduction\n\nThe tourism and hospitality sector has been significantly shocked by the COVID-19 pandemic, presenting a range of challenges for businesses and hotels due to decreased global mobility (Raki et al., 2021). In order to survive, firms and hotels have focused on short-term gains, which has sometimes resulted in questionable practices that put consumer well-being at risk (He and Harris, 2020). Providing innovative products and services to meet the diverse demands of customers is crucial for success in the highly competitive tourism and hospitality industry (Horng et al., 2016). Employee creativity and proactivity play a main significant key role in an organization’s competitive advantage, and therefore, companies should seek to increase employee proactivity to gain an edge (Horng et al., 2016). Saleem et al., (2023) found that job agility, reorganization, and heightened demands entail a proactive behavior from individuals, presenting significant opportunities for high performance in organizations. Callanan et al. (2017) emphasized that significant structural changes in organizational settings necessitate a relatively high level of employee contribution, knowledge, initiative, and proactivity. As a result, there is now a greater dependence on proactive employee behaviors (PWB) (Matsuo, 2022) in response to these changes.\n\nIn the hospitality and tourism business, which is both highly competitive and constantly changing, employees must display proactive work behavior to fulfill the evolving demands of customers and the industry (Wang and Yang, 2021). Proactive work behavior (PWB) involves taking initiative and engaging in self-starting actions to enhance work performance and contribute to a corporation’s success (Hou and Huang, 2021). This behavior includes anticipating, identifying, and acting on opportunities or challenges before being prompted or asked to do so (Bilal et al., 2021). Proactive employees exhibit characteristics such as taking responsibility, suggesting innovations, seeking feedback, and exceeding job requirements to achieve goals (Cui and Li, 2021). According to Bilal et al. (2021), employees who display proactive work behavior take the initiative to identify and address problems, propose innovative solutions, and actively seek opportunities for improvement. Wu et al. (2018) have conceded that proactive work behavior is advantageous for corporations as it leads to increased organizational effectiveness, innovation, and performance. ZHANG et al. (2022) found that PWB is associated with positive results such as enhanced job performance, creativity, job satisfaction, and career success. Proactive work behavior is particularly crucial in the hospitality and tourism business, where customer demands and market trends are constantly changing (Wang and Yang, 2021). Soomro et al. (2016) indicated that employees who exhibit proactive behavior can anticipate and respond to changing customer needs, identify service improvement opportunities, and further contribute to the corporation’s competitiveness and success.\n\nPL is a style of leadership that involves interrelated yet seemingly competing behaviors to highlight competing workplace pressures over time and simultaneously (Volk et al., 2022). According to Zhang et al. (2021), PL has gained extensive consideration in recent years due to its effectiveness in managing complex environments and dealing with organizational paradoxes. Amason (1996) emphasized that leaders who practice PL integrate opposing behaviors rather than choosing one over the other to navigate contradictory demands. This leadership style requires leaders to balance competing priorities, perspectives and approaches to achieve desired outcomes (Derksen et al., 2019). Research indicates that PL can have positive consequences on various outcomes, including leaders’ task performance, adaptive performance of employees, and employee task performance (Chen et al., 2021; Zhang et al., 2021; Li and Ding, 2022). Derksen et al. (2019) point out that PL can enhance employee task performance by strengthening employees’ sense of responsibility, motivation, and engagement. In the hospitality and tourism industry, where managing competing demands, adaptability, and flexibility are essential, it can argue that PL may play a significant role in encouraging PWB among employees (Qiang et al., 2023). By balancing competing demands and embracing contradictions, leaders who practice PL can create an environment that encourages employees to take the initiative, think innovatively, and proactively contribute to the organization’s success (Zhang et al., 2022a). This may also enhance PPCF.\n\nPPCF refers to the degree to which employees feel that their company appreciates their inputs and contributions and consequently prioritizes their well-being (Yu, 2022). When employees believe that their expectations are being met and that their employer values their contributions, they are more likely to exhibit proactive behaviour and engage in discretionary activities that have value to the organization (Topa et al., 2022). The psychological contract is an unwritten concept that describes employees’ expectations and beliefs about what they will receive from their employer in exchange for their contributions (Patrick, 2008). These expectations may include job security, opportunities for development and advancement, fair treatment, recognition, and a positive work environment (Wu and Chen, 2015). In the tourism and hospitality industry, perceived psychological contract fulfilment is particularly crucial because it plays a significant role in shaping employees’ attitudes and behaviours at the workplace (Yu, 2022), which can ultimately impact the quality of service provided to customers.\n\nIn sum, paradoxical leadership strives to satisfy employees’ psychological contract expectations to motivate them to engage in proactive behaviours. Accordingly, this study aims to (1) investigate the relationship between PL and PWB; 2) study the role of PL on PPCF; 3) analyse the correlation between PPCF and PWB; and explore the potential mediating role of PPCF in the relationship between PL and employee PWB in the hospitality and tourism business. Theories such as social exchange (SET) and psychological contract suggest that employees’ work behaviour is influenced by their perceptions of the employment relationship and the extent to which their organization fulfils its obligations. Therefore, it is possible to depend upon these theories to examine the relations among the study variables.\n\n\n2. Theoretical concepts and development of hypotheses\n\nPL refers to a leadership style that focuses on skillfully managing the inherent paradoxes within leadership and/or organizations (Julmi, 2021). It is characterized by leader actions that appear to be in competition with each other yet are interconnected both concurrently and across time (Sparr et al., 2022). In other words, paradoxical leaders are able to balance competing demands and find creative solutions to complex problems. PL is envisioned as a developing viewpoint aimed at comprehending how leaders assist followers in navigating paradoxes (Zhang and Han, 2019). PL is a relatively new concept in leadership research, and it has attracted increasing attention in recent years. One of the key features of PL is handling paradoxes and tensions inherent in leadership and organizations by using seemingly competing yet interrelated behaviors to make choices that do justice to both sides of the coin. It can be used as a sense giving tool for fostering readiness for change and performance oriented towards change, and it involves the ability to enact these behaviors simultaneously and over time (Zhang et al., 2015; Miron-Spektor et al., 2018; Sparr et al., 2022), some of the paradoxes that paradoxical leaders may need to manage include the following: Balancing accountability with rapport: Leaders must find a equilibrium between upholding accountability and nurturing positive relationships. Prioritizing rapport without enforcing accountability can hinder achieving peak performance (Boemelburg et al., 2023). Balancing autonomy with monitoring: Leaders must allow their teams to have autonomy, yet they must also monitor their employees (Julmi, 2021). Balancing control with autonomy: Leaders needs to balance the need for control and direction with the need for empowerment and autonomy (Julmi, 2021).\n\nThe majority of studies on PL have concentrated on its favorable impact within organizations, leading to enhancements in various areas such as performance, creativity, commitment, competitiveness, workplace environment, and career success, as demonstrated by different researchers (Amason, 1996; Smith, 2014; Knight and Harvey, 2015; Knight and Paroutis, 2017; Derksen et al., 2019). Moreover, studies have demonstrated that PL yields favorable outcomes for employees, including enhanced work attitudes, heightened work engagement, improved work role performance, increased creativity, and more innovative behaviors, as documented by multiple researchers (Zhang et al., 2015, 2022a; Garg, 2016; Fürstenberg et al., 2021; Yang et al., 2021). In essence, due to its effectiveness in navigating the complex environments faced by contemporary organizations, PL has widely been regarded as a potent leadership style (Zhang et al., 2015; Miron-Spektor et al., 2018). The minority of research on PL has studied its influence on employee Proactive Work Behavior (PWB). In our paper, we suggest a positive relationship between PL and PWB based on its beneficial impact on different aspects of employees work attitudes and performance.\n\nPWB can be defined as “the act of taking initiative to improve current circumstances or create new ones, challenging the status quo instead of passively adapting to present conditions (Bilal et al., 2021). It encompasses self-starting work behavior, implementing changes, and taking action to achieve goals (Parker et al., 2010). Proactive behavior refers to an employee taking initiative in bringing about self-directed and future-focused changes in their work environment or job responsibilities (Cui and Li, 2021). According to this definition, proactive behavior is characterized by three characteristics: “self-initiation, future focus, and change orientation”. Grant and Ashford (2008) illustrated that when employees are proactive at work, they Think, observe, strategize, fore-cast, and proactively act. According to Urbach (Urbach et al., 2021), the PWBs are differentiated by various types such as personal initiative, taking charge, voice, and individual innovation. Essentially, research has consistently revealed significant correlations between PWBs and individual characteristics, such as cognitive ability and self-efficacy, as well as job characteristics, such as job control, and organizational factors, such as leadership that promotes transformation and an organizational environment that encourages change and forgives mistake (Fay and Hüttges, 2017; Strauss et al., 2017; Zacher et al., 2019).\n\nAs mentioned previously, there is no studies that examined a direct relationship between PL and PWB in the field of tourism and hospitality, but there are some studies that tested the rapport between PL and PWB indirectly and in other fields other than tourism and hospitality. some of the relevant papers are as follows. Sparr et al. (2022) have proposed that PL improves employee task performance by strengthening their proactivity. A study by Kundi et al. (2023) have indicated that PL exerts both immediate and mediated impacts on employee performance. This encompasses job performance within designated roles, alongside supplementary behaviors like innovative work conduct and expressing opinions. These effects are predominantly channeled through employee work engagement. A study by He and Yun (2022) has suggested that PL significantly contributes to positive outcomes in terms of unethical pro-supervisor behavior. The connection between PL and immoral pro-supervisor actions is partly intermediated by the supervisor-subordinate dynamic. Furthermore, follower mindfulness assumes a moderating function in the association between PL and supervisor-subordinate interaction. Bilal et al. (2021) conducted a study using the self-determination theory to test the extent to which proactive personality moderates the relationship between work un-certainty and proactive work behavior, as well as strengthens the relationship between entrepreneurial leadership and psychological well-being (PWB). Bilal et al. research findings indicated that entrepreneurial leadership initially diminished work-related uncertainties, leading to subsequent enhancements in employees’ proactive work conduct. The outcomes also underscored that the influence of entrepreneurial leadership on PWB was mediated by work uncertainty. Additionally, the connection between work uncertainty and proactive work behavior was influenced by proactive personality, with a significant correlation emerging only when proactive personality traits were less pronounced. Furthermore, through moderated mediation analysis, it was evident that individuals with lower levels of proactivity placed more confidence in the proactive nature of entrepreneurial leadership in comparison to their highly proactive counterparts within the workplace. Boonyarit (2023) carried out an investigation and revealed that self-leadership demonstrates a positive correlation with two forms of PWB: assuming initiative and personal innovation. Furthermore, self-leadership exhibited favorable connections with psychological empowerment and the breadth of roles one believes they can effectively perform (RBSE).\n\nBased on what was previously mentioned, this study could provide evidence that demonstrates the link between PL and PWB. Accordingly, researchers would like to propose that\n\nPL is positively associated with PWB.\n\nPsychological contract theory is built upon the principles of social exchange theory, which is a social psychological concept that explains how individuals engage in social interactions based on mutual benefits and obligations (Aranda et al., 2018). Psychological contract fulfilment encompasses an individual’s personal convictions regarding the mutual commitments and advantages forged within a give-and-take association, such as employment within an organizational context (Topa et al., 2022; Hammouri et al., 2022; Rodwell et al., 2015). According to Coyle-Shapiro et al. (2019), it involves shared beliefs, perceptions, and implicit obligations between an employer and an employee, which shape the practicality of the work to be performed and establish the dynamics of the relationship. Hafez Mahmoud Gharib and Ahmed Khairy (2019) declared that the psychological contract is an informal agreement that is not typically documented in writing. Its contents and obligations are fulfilled through employees’ interactions with their organization. Ultimately, psychological contract fulfilment is a crucial factor in the employee-employer relationship, which can influence the quality of the relationship and the employee’s outcomes.\n\nThe available literature indicates that there is a dearth of research on the association between PL and PPCF in the tourism and hospitality domain. Nevertheless, some relevant studies suggest that there could be an indirect correlation between these two constructs. For instance, Huertas-Valdivia et al. (2019) investigated the impact of various leadership styles on the job performance of hospitality employees and observed that PL exhibited a positive correlation with employees’ psychological empowerment. Although this research did not directly explore the relationship between PL and PPCF, it implies that PL could potentially influence employees’ attitudes and perceptions in a favourable manner. The findings of a study by He and Yun (2022) emphasized that PL has a direct positive effect on Employee Loyalty, and this effect is partially explained by the role of job satisfaction in mediating the relationship between paradoxical leadership and employee loyalty. While this study did not investigate the link between PL and PPCF directly, being Employee loyalty can be considered a component of psychological contract fulfilment as explained by Hart and Thompson (2007) may imply that there is an indirect correlation between PL and PPCF. Oorschot et al. (2021) suggest that leaders, and leadership styles in particular, have the ability to impact the psychological contracts of employees. Given that PL is widely recognized as an effective style of leadership styles navigating the complex environments encountered by modern organizations (Zhang et al., 2021), this could suggest a potential correlation between PL and PPCF.\n\nConsidering the significance of both PL and PPCF in the service industry, it would be beneficial to explore the potential relationship between these constructs in the context of tourism and hospitality. The tourism and hospitality sector are renowned for its exceptional quality of service and consumer satisfaction, and effective leadership is crucial for managing employee expectations and obligations in this industry. Therefore, research in this field could shed light on the role of PL in enhancing PPCF in tourism and hospitality, which could contribute to improving job satisfaction, organizational commitment, and performance in this sector.\n\nAs previously noted, there is a gap in research regarding the specific relationship between PL and PPCF in the tourism and hospitality industry. Social Exchange Theory could be applied to address this gap. According to Ahmad et al. (2023), this theory posits that individuals are motivated by their expectations of rewards and outcomes. In the context of PL and PPCF in tourism and hospitality, this theory could be used to examine how PL behaviours influence employee expectations of rewards and outcomes, and how these expectations impact PPCF. Based on this discussion, the following hypothesis is proposed\n\nPL is positively associated with PPCF.\n\nThe search results reveal that there is a scarcity of research that explicitly investigates the connection PPCF and PWB within the tourism and hospitality industry. Nonetheless, a very few studies have indirectly highlighted the relationship between PPCF and work behaviour more broadly, as well as in other sectors. Here are some relevant academic papers:\n\nOne study by Noble-Nkrumah et al. (2022) investigated the interplay between job autonomy and employee trust in relation to the connection between PPCF and work behaviour within international non-governmental organizations. The research revealed a favourable correlation between PPCF and work behaviour, with job autonomy and employee trust functioning as moderators in enhancing this positive association. According to Hetet et al. (2023) and Bilal et al. (2021), work behaviour can be categorized as either in-role behaviour or extra-role behaviour, with proactive work behaviour falling under the latter category. Proactive work behaviour entails self-initiated and forward-looking actions aimed at enhancing existing conditions or establishing new ones. With this in mind, it can be deduced that there exists an indirectly positive correlation between PPCF and proactive PWB.\n\nAnother study by Yu (2022) investigated the effects of PPCF on employees’ work-related attitudes and behaviours (specifically work engagement, innate motivation, and emotional commitment) amidst the COVID-19 pandemic. The study found that psychological contract fulfilment positively influenced employees’ work behaviour during the pandemic. While this study does not directly refer to the relationship between PPCF and PWB, it may be concluded that psychological contract fulfilment positively influences proactive work behaviour, given that proactive work behaviour is a specific type of work behaviour.\n\nTherefore, while there may not be specific studies directly examining the relationship between PPCF and PWB in the tourism and hospitality business, the existing research attempts to bridge the gap and explore the relationship between PPCF and PWB more comprehensively. These points lead to the following hypothesis:\n\nPPCF is positively associated with PWB.\n\nPrevious studies in the tourism and hospitality business have not explored the relationship between PPCF, PL, and PWB. However, based on the information provided about PL, PWB, and PPCF, the connection between PL and employee proactive work behaviour (PWB) can be elucidated through the mediating effect of PPCF. PL can have either positive or negative impacts on employee behaviour. On the one hand, PL can encourage employees to embrace ambiguity, think critically, and challenge traditional norms, which can foster PWB. On the other hand, the contradictory nature of its leadership practices may create tension or confusion. In this relationship, PPCF plays a mediating role. When employees perceive that their organization fulfils the promises and obligations outlined in their psychological contract, they develop a sense of trust and reciprocity. This builds their commitment to the organization and motivation to engage in proactive behaviours. Thus, higher levels of PPCF strengthen the positive relationship between PL and PWB. In essence, PPCF explains how PL influences employee behaviour and encourages proactive work. The inclusion of PPCF as a mediator between PL and PWB provides a comprehensive understanding of how leadership behaviours affect employees’ proactive work behaviours. It highlights the importance of organizational fulfilment of psychological contracts in promoting desirable employee outcomes. Based on the previous discussion, a possible hypothesis could be.\n\nPPCF mediates the association between PL and PWB.\n\nBased on a review of previous literature and the study hypotheses that were proposed, a model for the study was designed, as shown in Figure 1.\n\nThe figure shows the study hypotheses: H1. Paradoxical Leadership (PL) is positively associated with Employee Proactive Work Behavior (PWB); H2. PL is positively associated with Perceived Psychological Contract Fulfillment (PPCF); H3. PPCF is positively associated with PWB; H4. PPCF mediates the association between PL and PWB.\n\n\n3. Method\n\nTo examine hypotheses, we gathered data from employees of hotels in Sharm El-Sheikh and Tourism companies and travel agencies in Cairo, Egypt, using a questionnaire tool. Because they had sufficient understanding to answer the survey questions, employees with at least 3-years of experience were qualified to participate. We instructed our postgraduate colleagues enrolled in our colleges and working in the study’s sample hotels and companies to connect with their HRMs to help us complete the questionnaire. We conducted “multi-wave and multi-source surveys” using the questionnaires, which reduced typical technique bias (Podsakoff et al., 2012). A time-lagged study process was operated, with two data waves collected from our sample employees during two-month intervals. Data were assembled from February to April 2023, performing “convenience sampling and drop-and-collect” methods. Employees measured paradoxical leadership (PL) and demographic data in the first wave survey. The second was conducted one months later, and the Psychological Contract Fulfilment (PPCF) and employee proactive work behaviour (PWB) variables were measured. In both two waves of surveys, 500 questionnaire forms were distributed. After eliminating the incompetent responses, 338 were considered, with an efficient reply rate of 67.6%. The study sample consisted of 62 females (18.3%) and 276 males (81.7%). The participants’ ages ranged mostly between 24 and 52. The full set of data is available on Zenodo (https://zenodo.org/records/11400950) and is freely available for non-commercial users (Zenodo, 2023).\n\nThe literature was consulted and used to create questionnaires for all variables. All variables were assessed using a 5-point Likert scale. The 22 items suggested by Zhang et al. (2015) were used to operationalize the PL variable. The PL scale items are broken down into five dimensions, 5-items for each of “Treating subordinates uniformly while allowing individualization,” “Combining self-centeredness with other-centeredness,” and 4-items for each of “Maintaining decision control while allowing for autonomy,” “Enforcing work requirements while allowing flexibility,” and “Maintaining both distance and closeness.” The PAB was measured by a 13-item suggested by Parker and Collins (2010) distributed on four dimensions; 3 items for each of “Taking charge,” “Problem prevention,” and “Individual innovation,” and four items for “Voice.” For the PPCF, seven items were used from the study of Tseng and Wu (2017). Additionally, to increase their clarity and comprehension, the survey questions were transcriptions and edited. Nineteen individuals, including nine academics and ten business executives, tested the validity of the survey to verify its reliability. There was no alteration made to the survey’s content during these procedures.\n\nPartial least squares (PLS) were used by operating the smartPLS version 4.0 (https://www.smartpls.com/) to perform structural equation modelling (SEM) to test the suggested model (the software offer a trail free full version for one month). The PLS technique is fitting when the main investigation’s aim is to foresee one or more tested variables rather than to validate a formerly established theoretical model (Hair et al., 2017). Therefore, this method is suitable for the current study because it tests relationships between the PL and PAB, considering the mediating effect of the PPCF. Additionally, the PLS is a productive tool across a broader range of sample sizes, and also it helps to construct a more complex and advanced model with fewer data constraints (Hair et al., 2011). The PLS-SEM processing, according to Leguina (2015), passes across two steps, namely, (2) measurement modelling or outer model assessment and (1) structural modelling or inner model assessment.\n\n\n4. The Results\n\nThe measuring model assesses the “convergent validity” (CV) and “discriminant validity” (DV) to determine the quality of the data. The CV evaluates the connections between the study’s indicators by performing “Cronbach’s alpha” and must exceed the threshold of 0.50 (Leontitsis and Pagge, 2007), “composite reliability (CR)”, which is greater than 0.60 (Fornell and Larcker, 1981), “Average Variance Extracted” (AVE), which should not be less than 0.50 (Hair et al., 2011), and “factor loading”, also, preferably greater than 0.50 (Afthanorhan, 2013) as assessment standards. Additionally, DV claims that when using various methods to measure other factors, the measured results must be distinguishable. According to Fornell and Larcker (1981), If a factor’s AVE is greater than the association between that factor and other factors in the suggested model, the factor meets the statistical requirements for “discriminant validity.\" In addition, a number of scholars evaluated the “Heterotrait-Monotriat” ratio of correlation (HTMT) to determine the “discriminant validity” in response to the many criticisms made of “Fornell and Lacker’s criterion.” (Gold et al., 2001).\n\nTable 1’s CV values display that every specified minimum and/or maximum level was accepted, proving the validity of the proposed outer model. Also, the values of AVE and HTMT, which are portrayed in Table 3 and Table 4, respectively, also met the recommended norms, proving that their “discriminant validity” is adequate. Also, Table 2 shows that “an item’s loading within its factors is greater than any cross-loadings with other factors, guaranteeing the DV”.\n\nThe “variance inflation factor” (VIF) is utilised in this study to examine the collinearity regards to ascertain the presence of collinearity issues among variables and to stop the impact of variables on the offered model’s contribution. According to Hair et al. (2011), reducing multicollinearity is unnecessary for VIF values under 5. Additionally, the “coefficient of determination” (R2) and “Stone-Geisser’s” (Q2) were operated to gauge how satisfactorily the regression model explained the data. R2 results of 0.20 are regarded as adequate level in behavioural studies (Hair et al., 2011). The Q2 scores also met the suggested norm value of 0.0 (Hair et al., 2014). The VIF, R2, and Q2 findings are presented in Table 5.\n\nUnlike “covariance-based structural equation modelling” (CBSEM), the PLS approach lacks a range of statistical parameters for validating models, such as X2 and other indicators of model fit (Henseler and Sarstedt, 2013). To solve this problem, “Goodness of Fit” (GoF) has been proposed as a successful model validation technique (Tenenhaus et al., 2005). According to Mital et al. (2018) and Tenenhaus et al. (2005), the GoF can be calculated by taking the value of the square root of the average variance extracted multiplied by the R square value.\n\nAs per Tenenhaus et al. (2005), GoF scores of 0.1, 0.25, and 0.36, respectively, denote modest, medium, and high GoF. The GoF value for the model constructed in this study is 0.558, indicating a notably high GoF index. The “Standardised Root Mean Square Residual” (SRMR), which compares variances in observed correlations, was used to further assess the model’s validity. Model fit is considered acceptable when the SRMR value is less than 0.1 (Hu and Bentler, 1998). The proposed model’s SRMR value is 0.095, which indicates a satisfied model fit.\n\nUpon validating both the external and internal models, the study progressed to judge the formulated hypotheses. Utilizing SmartPLS v.4, a bootstrapping process with 5000 iterations was conducted to calculate (β) the regression weights, t-scores, and P-values associated with the direct, the indirect, and the mediating paths. The analysis encompassed four main hypotheses, comprising of 3 direct hypotheses and 1 mediating hypothesis, as presented in Table 6.\n\nData portrayed in Table 6 and Figure 2 demonstrated that the PL has a positive significant influence on PAB (β = 0.293, t = 3.388, p<.001) and PPCF (β = 0.680, t = 13.328, p< .001), confirming H1 and H2. The results further supported H3 by showing that the PPCF variable positively influenced PAB at β= 0.420, t=5.637, and p.001. Furthermore, at β= 0.286, t = 4.800, and p< .001, the PPCF variable mediated the link between PL and PAB, supporting H4.\n\nNote: UI ➔“Treating subordinates uniformly while allowing individualization”; SOC➔ “Combining self-centeredness with other-centeredness”; DCA➔“Maintaining decision control while allowing for autonomy”; WRF ➔“Enforcing work requirements while allowing flexibility”; DC ➔ “Maintaining both distance and closeness”.\n\n\n5. Discussion & Implications\n\nThis study endeavors to answer the call for more investigations on paradoxical leadership in the contemporary workplace and demonstrate how it influences proactive and innovative work behavior (Waldman and Bowen, 2016; Miron-Spektor et al., 2018; Zhang et al., 2022b). Our research operates data collected from the hospitality and tourism industry in Egypt, a developing country, to 1) investigate the relationship between PL and PWB; 2) study the role of PL on PPCF; 3) analyze the correlation between PCF and PWB; and explore the potential mediating role of PPCF in the relationship between PL and employee PWB in the hospitality and tourism industry. As a result, our empirical investigation effectively achieved its goals and aims, contributing to the ongoing discourse in paradoxical leadership literature and advancing theoretical frameworks through the introduced model. The study’s findings demonstrated a positive impact of PL on PAB (H1). Furthermore, this leadership style bolstered employee task performance by fostering greater proactivity (Sparr et al., 2022). Most studies on paradoxical leadership have concentrated on its favorable impact on organizations by enhancing performance, creativity, commitment, competitiveness, workplace environment, and career success (Amason, 1996; Smith, 2014; Knight and Harvey, 2015; Knight and Paroutis, 2017; Derksen et al., 2019). Moreover, numerous empirical studies within the domain of tourism and hospitality have explored the beneficial effects of paradoxical leadership on employees, encompassing aspects such as work attitudes, engagement, job performance, creativity, and innovative behavior (Zhang et al., 2015, 2021; Garg, 2016; Fürstenberg et al., 2021; Yang et al., 2021). Accordingly, PL succeeded in positively influencing the PWB.\n\nSimilarly, the study discovered that PL positively affects PPCF (H2). In general, paradoxical leader behaviors seek to accommodate all contradictions to achieve balance within the hotel’s work environment, which leads to satisfaction with the expected terms of the employees’ psychological contract (Oorschot et al., 2021; Yang et al., 2021). This is also supported by the findings of Ebrahimi et al. (2019) study, which showed that paradoxical leadership could potentially influence employees’ attitudes and perceptions in a favourable manner.\n\nLikewise, the results proved that the PPCF positively affected PAB (H3). Consistent with this result, the study of Yu (2022) revealed that perceived psychological contract fulfillment affects employees’ work attitudes and behaviors (i.e., work engagement, intrinsic motivation, and affective commitment) (Yu, 2022). In other contexts, studies indicated that psychological contract breach leads employees to reduce their proactive behaviours and diminish both prosocial and proactive work behaviours (ZHAO et al., 2007; Bal et al., 2011).\n\nOne of the primaries aims of our study was to investigate how perceived psychological contract fulfillment (PPCF) acts as a mediator between paradoxical leadership (PL) and proactive employee behavior (PAB). The study’s results indicate that PPCF effectively mediated the relationship between PL and PAB (H4). The mediation relationship was a result of the significant direct correlation between the study variables that proved the significant link between PL, EWB, and PPCF and between PPCF and EWB.\n\nFinally, the study offers essential insights for practical implementation in management. It suggests that leaders within the hotel and tourism sector should prioritize the enhancement of perceived psychological contract fulfillment, foster empowering leadership approaches, and strike a harmonious equilibrium in employing paradoxical leadership practices. These actions are advised to cultivate favorable work outcomes, including proactive work behavior, within the realm of hospitality and tourism. They should also consider individual differences and ensure employees’ psychological contracts are fair and just. Additionally, hospitality and tourism sector leaders should ensure fairness and justice in the treatment of employees.\n\n\n6. Conclusion\n\nEmploying the PLS-SEM methodology, this article has highlighted the influence of PL on PAB, with a specific emphasis on the intermediary functions of PPCF. The results of this study suggest that the connection between paradoxical leadership and proactive employee behavior in the hospitality and tourism sector is partially mediated by perceived psychological contract fulfillment. Paradoxical leadership has a positive influence on perceived psychological contract fulfillment, which in turn affects employee proactive behavior. A positive correlation has been identified between perceived psychological contract fulfillment and proactive employee behavior within the hotel and tourism industry. Paradoxical leadership can have implications for hospitality and tourism industry employees, and some behaviors that help hotels and tourism businesses compete may have paradoxical implications for employees. It is essential to acknowledge that the precise outcomes and implications regarding the intermediary function of perceived psychological contract fulfillment within the interplay of paradoxical leadership and proactive employee work behavior may necessitate additional research and exploration, especially within the context of the hospitality and tourism industry.\n\n\nEthics and consent\n\n“Institutional Review Board Statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Deanship of Scientific Research Ethical Committee, King Faisal University (project number: grantA167, date of approval: 25 April 2022)”.\n\n“Informed Consent Statement: A written informed consent was obtained from all subjects involved in the study”. This was done by accepting the following statement at the beginning of the data collection process “I agree to take part in this study, and understand that my participation is voluntary, that I can choose not to participate in part or all of the project, and that I can withdraw at any stage of the project without being penalized or disadvantaged in any way”.",
"appendix": "Data availability\n\nZenodo: Paradoxical Leadership and Employee Proactive Work Behavior: Exploring the Mediating Role of Perceived Psychological Contract Fulfillment, https://zenodo.org/doi/10.5281/zenodo.11206057 (Elshaer et al., 2024).\n\nThe project contains the following data:\n\n• Final paradoxical leadership.xlsx\n\nThis data was collected and formed by the authors of this paper. The license for this data is CC-BY 4.0 International.\n\nSoftware availability: the employed software is PLS-SEM v4 is available for one month as a free trial from (https://www.smartpls.com/).\n\n\nReferences\n\nAfthanorhan W: A comparison of partial least square structural equation modeling (PLS-SEM) and covariance based structural equation modeling (CB-SEM) for confirmatory factor analysis. International Journal of Engineering Science and Innovative Technology. 2013; 2: 198–205.\n\nAhmad R, Nawaz MR, Ishaq MI, et al.: Social exchange theory: Systematic review and future directions. 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}
|
[
{
"id": "300309",
"date": "15 Jul 2024",
"name": "Yuping Dai",
"expertise": [
"Reviewer Expertise Organizational behavior:Employee innovative behavior",
"organizational citizenship behavior",
"employee proactive personality",
"leadership",
"employee green behavior",
"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\nI read your paper excitedly. employees’ proactive work behavior is an important issue in tourism and hospitality sector. Overall, the structure of this article is complete, the logic is coherent, and it shows a certain degree of innovation. The data analysis is reasonable. But this paper needs some adds and amendments. My suggestions are :\n1.The paper is well written and managed. However, authors need to proceed to a certain proofreading of the document to avoid some syntax or spelling errors. 2. In the \"Theoretical concepts and development of hypotheses\" section, H1 is not well substantiated. The study needs to prove the relationship between PL and PWB, yet the author repeatedly mentions entrepreneurial leadership and employee behavior. What is the connection between PL and entrepreneurial leadership? How can the relationship between entrepreneurial leadership and employee behavior be used to prove the link between PL and PWB? Additionally, in this section, PWB is an abbreviation for \"proactive work behavior,\" so why is it referred to as PWB after \"psychological well-being\"? This seems confusing, the authors should carefully review this. 3. In the \"Measures\" section, \"The PAB was measured by...\" should it be PAB or PWB? 4. In the \"Discussion & Implications\" section, the author sometimes uses PCF and sometimes PPCF. Please ensure the abbreviations are consistent throughout. 5. In the 'Discussion & Implications' section, the authors provide an in-depth analysis of their findings, comparing them to relevant studies. However, the theoretical contributions could be more clearly articulated. Additionally, the managerial suggestions lack practicality.\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": [
{
"c_id": "12488",
"date": "22 Oct 2024",
"name": "Ibrahim Elshaer",
"role": "Author Response",
"response": "Thank you for these comments. We have fully complied with all your constructive comments. 1- We thank the reviewer for this comment. We have stated the research purpose and objectives of the study in the introduction section 2- We have clearly and briefly introduced the study variables in the introduction 3- Thank you for your feedback. As for this valued comment, and depending upon a comment by Reviewer 1, we have replaced using self-determination theory by social cognitive theory, and explained how the study incorporated all study variables and their relationships into these three theories as follows; Concepts from theories like social cognitive theory, psychological contract theory, and social exchange theory (SET) propose that employees' work behavior is shaped by their perceptions of the employment relationship and how well their organization fulfils its commitments. Social cognitive theory guides the investigation into the connection between PL and PAB. Psychological contract theory elucidates the link between PL and PPCF. Lastly, social exchange theory is employed to assess the relationship between PPCF and PAB. 4- We have reordered this section to be as you mentioned, Section 5: Discussion, Section 6: Conclusion, and Section 7: Implications 5- We have added a separate section which is section 8 as follows; Limitations and Future Studies The study was conducted in a specific context (hospitality and tourism industry in Egypt). The generalizability of the findings to other industries or cultural contexts remains to be tested. Cross-cultural comparisons would be valuable to understand the boundary conditions of the proposed relationships. The study's reliance on data from a specific industry in a developing country may restrict the breadth of the conclusions drawn, emphasizing the need for further research with more diverse samples. It is essential to acknowledge that the precise outcomes and implications regarding the intermediary function of perceived psychological contract fulfillment within the interplay of paradoxical leadership and proactive employee work behavior may necessitate additional research and exploration, especially within the context of the hospitality and tourism industry. Comparative studies across different countries or regions could shed light on how cultural factors influence the effectiveness of paradoxical leadership. Investigating potential moderating variables that could influence the relationship between paradoxical leadership and employee outcomes would enhance the understanding of these dynamics further. 6- we have supported the literature review with the advised references"
}
]
},
{
"id": "310527",
"date": "05 Sep 2024",
"name": "Marymagdaline Enow Mbi Tarkang Mary",
"expertise": [
"Reviewer Expertise Social sciences and more focus on tourism and hospitality",
"organizational leadership organizational behavior",
"Human resource management",
"marketing",
"service quality",
"customer satisfaction in the service industry sustainable employee development",
"Employee sustainability",
"employee relations and sustainability in business"
],
"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\nComment For F100000 Dear Editor, thank you for the opportunity to review this manuscript titled \" Paradoxical Leadership and Employee Proactive Work Behavior: Exploring the Mediating Role of Perceived Psychological Contract Fulfillment\". I will also like to thank you for your patience The manuscript has been well written, however, I have some few suggestions for authors to take into consideration before this paper can be considered for indexing.\nThe introduction needs more elaboration and concision, however, also I suggest the authors to clearly state the research purpose and objectives of the study in the introduction section Authors can clearly but briefly introduce study variables well in the introduction The study have used three different theories self-determination theory, Psychological contract theory and social exchange theory. How did the study incorporate all study variables and their relationships into these three theories. The methodology has been well written and the results well explained Can the conclusion come after the discussion and before the implications? Can authors give the limitations of the propose recommendations for future studies? This can be proofread again for better understanding and clarity. For greater improvement on the literature I would like the authors to cite the following articles\n\n(Alola et al.,2023)(Ref-1) (Tarkang et al.,2020)(Ref-2)\nAuthors should take out time to carefully address the above concerns, then can the manuscript be considered for approval\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\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": "12489",
"date": "22 Oct 2024",
"name": "Ibrahim Elshaer",
"role": "Author Response",
"response": "1- We thank the reviewer for this comment. We have stated the research purpose and objectives of the study in the introduction section 2- According to your advice, the entire paper has been proofread. 3- Thank you for this remark. We have modified this section to be as follows, As mentioned previously, there is no studies that examined a direct relationship between PL and PAB in the field of tourism and hospitality, but there are some studies that tested the rapport between PL and PAB indirectly and in other fields other than tourism and hospitality. some of the relevant papers are as follows. Sparr et al. (2022) have proposed that PL improves employee task performance by strengthening their proactivity. A study by Kundi et al. (2023) have indicated that PL exerts both immediate and mediated impacts on employee performance. This encompasses job performance within designated roles, alongside supplementary behaviors like innovative work conduct and expressing opinions. These effects are predominantly channeled through employee work engagement. A study by He and Yun (2022) has suggested that PL significantly contributes to positive outcomes in terms of unethical pro-supervisor behavior. The supervisor-subordinate dynamic partly intermediates the connection between PL and immoral pro-supervisor actions 4-We unified the abbreviation to PAB. 5- We unified the abbreviation to PPCF. 6- The theoretical and practical implications are modified as follows, The theoretical implications of this study contribute significantly to the existing literature on paradoxical leadership by providing a deeper understanding of its effects on proactive and innovative work behavior. The research highlights the positive relationship between paradoxical leadership (PL) and proactive employee behavior (PAB), as well as the mediating role of perceived psychological contract fulfillment (PPCF) in this relationship. By integrating these concepts, the study advances theoretical frameworks related to paradoxical leadership and its influence on employee attitudes and behaviors, thereby enriching the discourse on how leaders can effectively navigate contradictions within the workplace. Furthermore, the findings support the notion that paradoxical leadership can enhance employee adaptability and performance by fostering a balanced approach that accommodates competing demands, which is essential in today’s dynamic work environments. From a practical standpoint, the study offers valuable insights for management within the hospitality and tourism industry. It emphasizes the importance of fostering an environment where perceived psychological contract fulfillment is prioritized, as this can enhance proactive work behavior among employees. Leaders are encouraged to adopt paradoxical leadership practices that strike a balance between control and empowerment, thereby creating a supportive atmosphere that encourages employees to voice their opinions and engage proactively. Additionally, the findings suggest that organizations should implement training and development programs to cultivate leaders who can effectively manage paradoxes and contradictions, ultimately leading to improved employee outcomes and organizational performance. By focusing on these practical implications, organizations can better navigate the complexities of modern workplaces and leverage the benefits of paradoxical leadership to drive innovation and adaptability."
}
]
}
] | 1
|
https://f1000research.com/articles/13-622
|
https://f1000research.com/articles/13-805/v1
|
16 Jul 24
|
{
"type": "Research Article",
"title": "TOP2DFVT: An Efficient Matlab Implementation for Topology Optimization based on the Finite-Volume Theory",
"authors": [
"Marcelo Araujo",
"Arnaldo Santos Júnior",
"Romildo Escarpini Filho",
"Eduardo Lages",
"Marcio Cavalcante",
"Marcelo Araujo",
"Arnaldo Santos Júnior",
"Romildo Escarpini Filho",
"Eduardo Lages"
],
"abstract": "The finite-volume theory has shown to be numerically efficient and stable for topology optimization of continuum elastic structures. The significant features of this numerical technique are the local satisfaction of equilibrium equations and the employment of compatibility conditions along edges in a surface-averaged sense. These are essential properties to adequately mitigate some numerical instabilities in the gradient version of topology optimization algorithms, such as checkerboard, mesh dependence, and local minima issues. Several computational tools have been proposed for topology optimization employing analysis domains discretized with essential features for finite-element approaches. However, this is the first contribution to offer a platform to generate optimized topologies by employing a Matlab code based on the finite-volume theory for compliance minimization problems. The Top2DFVT provides a platform to perform 2D topology optimization of structures in Matlab, from domain initialization for structured meshes to data post-processing. This contribution represents a significant advancement over earlier publications on topology optimization based on the finite-volume theory, which needed more efficient computational tools. Moreover, the Top2DFVT algorithm incorporates SIMP and RAMP material interpolation schemes alongside sensitivity and density filtering techniques, culminating in a notably enhanced optimization tool. The application of this algorithm to various illustrative cases confirms its efficacy and underscores its potential for advancing the field of structural optimization.",
"keywords": [
"topology optimization",
"compliance minimization problem",
"finite-volume theory",
"Matlab."
],
"content": "1. Introduction\n\nIn structural engineering, topology optimization is a technique that searches for the best material distribution inside an analysis domain based on an objective function and one or more constraints (Bendsøe and Sigmund, 2003). Therefore, topology optimization allows for the discovery of innovative and high-performance structural designs, which attracted the interest of mathematicians and engineers (Liu and Tovar, 2014). With the progressive development of computer technology and computational mechanics over the last decades, the structural topology optimization tools have gradually experienced improvements that allow the solution of medium and large-scale problems. In addition, topology optimization has become an effective strategy for generating innovative forms for additive manufacturing, architectural design, and engineering (Zhuang et al., 2023). In general, compliance evaluation has played an important role in topology optimization algorithms. Since the pioneer work of Michell (1904), who derived the optimality criteria (OC) method, and the reconstruction proposed by Bendsøe and Kikuchi (1988), a great part of the advances in topology optimization has been achieved by employing methodologies based on structural compliance minimization problems. Some studies on this field can still be found in Liu et al. (2023), Yi et al. (2023), Lee et al. (2023), Arruda et al. (2022), Bouajila et al. (2021), and Ferrari and Sigmund (2020).\n\nIn topology optimization algorithms, the interest is in determining whether we should put material or not, which generates a “black and white” design. Therefore, the structural material distribution is obtained by a binary “0-1”, where 0 indicates void and 1 indicates the presence of material. However, this kind of topology optimization algorithms lead to an integer programming problem, which has revealed to be an unfeasible approach for large scale topology optimization problems. An alternative approach is the SIMP (Solid Isotropic Material with Penalization) method, which has been extensively used due to its versatility, convergence, and ease implementation (Rozvany, 2009). In this approach, the material properties can be evaluated inside each element of the discretized domain, and the design variables are the elements’ relative densities. Therefore, the mechanical properties are modeled by the material relative density raised to a penalty factor that penalizes their intermediate values. Another interpolation scheme to penalize intermediate values of relative density is the RAMP (Rotational Approximation of Material Properties) method proposed by Stolpe and Svanberg (2001), which employs a concave penalty function to suppress these intermediate values in the objective function. Unlike the SIMP method, the RAMP model presents non-zero sensitivity at zero density, so this model is especially efficient to remedy some numerical difficulties presented in problems with very low densities (Deaton and Grandhi, 2014).\n\nDifferent authors have developed educational algorithms to design optimized topologies in the last two decades. The trailblazer top99 educational code written in Matlab proposed by Sigmund (2001) had promoted important impacts in the topology optimization field, such as teaching of topology optimization tools in undergraduate courses, building simple code for new researchers, and pioneering a new popular category of publications in the structural optimization field: educational articles self-containing compact codes for teaching and research (Zhou and Sigmund, 2021). Beyond the well-known top99 Matlab code, several computer tools for Matlab and other platforms are available, such as PETSc by Smit et al. (2021) and Aage et al. (2015) for Python; TopOpt app by Aage et al. (2013) for language C; Stutz et al. (2022), Aage and Lazarov (2013), and Borrvall and Petersson (2001) for C++ language; Liu et al. (2005) for Femlab; and Sokół (2011) for Mathematica. However, a significant part of the proposed educational algorithms for topology optimization is written in Matlab language, as top99neo by Ferrari and Sigmund (2020), an 88-line code for parametrized level-set method by Wei et al. (2018), top88 by Andreassen et al. (2011), top3d by Liu and Tovar (2014), PolyTop by Talischi et al. (2012), HoneyTop90 by Kumar (2023), a 115-line code for multi-material topology optimization by Tavakoli and Mohseni (2014), and GRAND by Zegard and Paulino (2014).\n\nIn the top99 topology optimization code, the performance of several operations can be increased by exploiting the strengths of Matlab, such as loop vectorization and memory preallocation, and by restructuring the program, as moving portions of code out of the optimization loop so they would be executed once (Andreassen et al., 2011). Therefore, Andreassen et al. (2011) have proposed an 88-line code in Matlab for compliance minimization by allocating these computational features (top88), which has substantially improved the computational performance of the optimization algorithm. Later, Liu and Tovar (2014) have extended this algorithm to three-dimensional problems by also placing other strategies for topology optimization of compliant mechanisms and heat conduction problems. With the evolution of topology optimization research field and Matlab, the top88 code has become outdated, which has motivated the publication of the new generation of the top99 code (top99neo) by Ferrari and Sigmund (2020), making some improvements inmet the assembly operations, accelerating the Optimality Criteria (OC) method, filters implementation, and extending to three-dimensional structures.\n\nAraujo et al. (2020a,b) propose applying the finite-volume theory for topology optimization considering compliance minimization. This theory has been shown to be numerically stable for optimization problems, especially its checkerboard-free property, even when a non-filtering technique is employed. Numerical stability is an essential feature of the finite-volume theory applied in topology optimization tools to obtain more reliable optimized topologies. Also, this technique has shown to be well suitable method for elastic stress analysis in solid mechanics, investigations of its numerical efficiency can be found in Araujo et al. (2021), Cavalcante et al. (2007a,b, 2008) and Cavalcante and Pindera (2012a,b). The satisfaction of equilibrium equations at the subvolume level, concomitant to kinematic and static continuities established in a surface-averaged sense between common faces of adjacent subvolumes, are features that distinguish the finite-volume theory from the finite-element method. Thus, in the finite-volume theory, the connections between adjacent subvolumes occur through subvolumes’ faces, which is more likely from the continuum mechanics point of view.\n\nThis contribution provides a new topology optimization tool for the analysis of 2D structures using the Matlab language, which starts from domain discretization and continues until data is post-processed. In addition, this is the first time a platform for optimizing structures using the finite-volume theory can be applied to medium and large-scale problems, besides obtaining checkerboard-free and mesh-independent designs. The topology optimization tool also incorporates the SIMP and RAMP methods and the sensitivity and density filters. Employing a symmetric modified stiffness matrix also represents an advance since it accelerates the algorithm and establishes a relation between resultant forces and displacements instead of tractions and displacements, which are energetically conjugated static and kinematic quantities. These improvements have dramatically reduced the computational cost and solved the oscillatory phenomenon issue through the RAMP approaches, especially compared with the results in Araujo et al. (2020a). More details about the implementation can be found in the GitHub link (https://github.com/fvt7782/Top2DFVT).\n\n\n2. Finite-volume theory\n\nIn general, the finite-volume theory employs the stress and displacement fields and imposes boundary and continuity conditions between adjacent subvolumes in an average-sense, which has guaranteed the checkerboard-free property discussed in Araujo et al. (2020a). Additionally, the differential equilibrium equations are locally satisfied in an average-sense (Araujo et al., 2021), and the displacement field in the subvolume is modeled by second-order polynomials defined in local coordinates (Cavalcante et al., 2007a). The presented formulation has its roots in the standard version of the finite-volume theory presented in Cavalcante and Pindera (2012a) for structured meshes formed by rectangular subvolumes. Fundamentally, the structural analysis problem involves mechanical quantities evaluation, as applied loads, internal forces, displacements, and strains. The main objective is determining the stress and displacements when structural discretized domains are employed, where stress-strain relation can be easily expressed.\n\nFigure 1 presents the analysis domain in x1−x2 plane, which is discretized in Nq subvolumes. The subvolume dimensions are l(q) and h(q) for q=1,…,Nq, where x1(q) and x2(q) represent the local coordinate system. Following Cavalcante and Pindera (2012a), the displacement of a subvolume q can be approximated by an incomplete quadratic version of Legendre polynomial expansion in the local coordinate system as follows:\n\nSimilarly, considering the application of Cauchy’s law and the plane stress state, the surface-averaged traction components at the subvolume faces can be evaluated as\n\nFollowing Araujo et al. (2020a), the local system of equations for a generic subvolume can be established as\n\nTherefore, the modified global system of equations can be written as\n\n\n3. Topology optimization problems for compliance minimization\n\nA significant portion of the progress in topology optimization has been made through the consideration of compliance minimization problems, whose concepts are well-established in the context of finite-element strategies. In this study, we implement the compliance minimization problem using linear elastic stress analysis based on the finite-volume theory. According to Araujo et al. (2021), the total work done by external loadings and the total strain energy of a deformed structure are equal for quasi-static analysis in the context of the standard finite-volume theory. As a result, the nested topology optimization problem for compliance minimization can be written as\n\nThe problem presented in Eq. (8) is solved with a nested iterative loop, where at each iteration, the displacement u¯ is computed by solving the modified global system of equations presented in Eq. (7). The two major material interpolation functions are implemented in the algorithm: SIMP (Sigmund, 2007) and RAMP (Stolpe and Svanberg, 2001). The Young’s modulus Eq(ρq) of each subvolume can be evaluated by the following expressions:\n\nwhere p and a are the penalization factors for SIMP and RAMP methods, respectively, E0 is the material stiffness, and Emin is the soft (void) material stiffness, which is a non-zero positive low value to avoid the singularity in the stiffness matrix. Figure 3 shows the concavity of the penalization functions performed by the SIMP and RAMP methods as presented by Eq. (9), where the ratio Emin/E0 is adopted as 10−9. The RAMP method presents a more gradual increase in its concavity when compared to the SIMP method, which softens the numerical response of this method. The function concavity observed in the RAMP method is smoother and presents a slower convergence to the limit relative density values (0 or 1), as observed in the green (RAMP for a=1) and blue (RAMP for a=2) lines, which incurs in a more gradual convergence for this method. On the other hand, the SIMP method concentrates the relative density values in 0 or 1, as observed in concavity of the orange (SIMP for p=2) and yellow (SIMP for p=3) lines, promoting a faster convergence to the black and white design.\n\nThe gradient of the compliance with respect to the subvolume density ρr can be determined by\n\nEmploying K¯(q)T=K¯(q), the Eq. (10) can be simplified to\n\nThe Eq. (11) can be rewritten as\n\nOnce ∂u¯p/∂ρr=0, the Eq. (12) can be simplified to\n\nThus, there are two cases, as described below.\n\nCase 1: prescribed displacement (Rp=0 and u¯p≠0), which implies in the maximization of C(ρ).\n\nCase 2: prescribed force (Rp≠0 and u¯p=0), which implies in the minimization of C(ρ).\n\nDifferentiating Rp=K¯puu¯u in relation to ρr, follows\n\nThus\n\nConsidering u¯p=0, follows\n\nThis implies\n\nThe proposed optimization problem is solved employing the OC method. Following Sigmund (2001) and Andreassen et al. (2011), a heuristic updating scheme identical to the scheme proposed in Bendsøe (1995) can be employed as\n\nThe damping factor can be employed to regularize possible oscillations during the optimization, mainly when no filtering techniques are employed. The parameter η is directly related to the method performance, once this affects the speed variation of Bqη (Montes, 2016). A high value for η can accelerate the optimization convergence process, which may cause oscillations in the displacement field for the low-density regions (Ma et al., 1993). Also, the adoption of minor values of η can prevent divergence in the topology optimization algorithm; however, this results in small changes in the design variables, which leads to a slower convergence process (Ma et al., 1993). The value of η that provides the faster convergence for the overall process is 1/2, so it is recommended to maintain the damping factor as close as possible of this value.\n\nAs discussed by Araujo et al. (2020b), the topology optimization problem based on the finite-volume theory is a checkerboard-free approach; however, it is observed the occurrence of the mesh-dependency numerical issue. As a result, for topology problems employing the finite-volume theory, filtering techniques are employed to circumvent the mesh dependence issue. Filtering techniques intend to regularize topology optimization numerical issues by using density or sensitivity-based methods. For the density-based methods, each subvolume is redefined by a weighted average of the densities in the subvolume neighborhood, which modifies the sensitivities after the finite-volume analysis. For the strategy based on sensitivity methods, the finite-volume theory analysis is performed, and the sensitivities are consistently calculated; subsequently, they are heuristically recalculated by weighted averaged functions of the sensitivities in the neighboring subvolumes (Sigmund, 2007).\n\nFor the sensitivity-based strategy, the employed filtering technique modifies the subvolumes’ sensitivities as follows\n\nThe density filter modifies, besides the sensitivities, the original densities ρq as follows\n\n\n4. Software description\n\nTop2DFVT is an algorithm developed to obtain optimized topologies using the finite-volume theory for linear elastic continuum structures. The first use of this algorithm performed by Araujo et al. (2020a) was based on the implementation suggested by the top99 code (Sigmund, 2001), where some operations, such as the filtering procedure and matrices assembly, dramatically increase the computational cost. Therefore, the main features of the top88 code are now explored in this version, such as loop vectorization and memory preallocation, which are strengths of Matlab explored in this program. Additionally, some parts of the code are moved out of the optimization loop, guaranteeing they are only performed once. From the top99neo code, the fsparse function is implemented for finite-volume theory matrices assembly, which guarantees a gain of computational efficiency by accelerating the preallocation of these large matrices. The program also explores two new advances in the OC method promoted by the top99neo code. The first advancement incorporates a better approximation for the initial guess of the interval of the Lagrange multiplier λ in the bisection method. This improvement reduces the number of iterations operated by the OC method by suggesting initial values closer to the final solution in the iterative process of the bisection method. The second advancement involves avoiding the application of a filter at each bisection step when checking the volume constraint with the physical field. This alternative reduces the processing time of each bisection iteration and represents another improvement inspired by the top99neo code.\n\nThe proposed algorithm is a collection of Matlab functions written in 175 lines, disregarding the commented lines, that implement the design domain, material properties, finite-volume theory analysis, topology optimization, mesh-independency filters, and post-processing. In the data initialization step, the design domain and material properties are defined as inputs to the topology optimization problem, and homogeneous rectangular subvolumes are adopted in the discretized domain. The relative density of each subvolume in the discretized domain is taken as constant. The finite-volume theory analysis is performed for structured meshes considering linear elastic materials for plane stress state. The gradient-based topology optimization problem for compliance minimization is solved employing the OC method, considering a move limit of 0.2. The stopping criterium is set up as follows: 1% of tolerance for the maximum change in the design variables between successive steps. Two mesh-independent filters are implemented: a sensitivity filter and a density filter based on the filtering approaches presented by Andreassen et al. (2011). Finally, the algorithm prints the obtained optimized topology and the investigated numerical aspects, such as the number of iterations, processing time, compliance estimations, etcetera.\n\nThe algorithm is initialized by entering the following line in the Matlab command prompt:\n\nwhere L and H indicate the horizontal and vertical analysis domain length, respectively, nx and ny are the number of subvolumes in the horizontal and vertical directions, respectively, volfrac is the prescribed volume fraction constraint, penal is the penalty factor, frad is the filter radius, ft specifies whether sensitivity filter (ft = 1), or density filter (ft = 2), or no filter (ft = 0), and varargin activates the use of the fsparse routine when set up as ‘fast’. In Top2DFVT.m file, the major sections are default parameters’ declaration, initialization of design variables, domain initialization, local stiffness matrix calculation, material interpolation, filtering initialization, topology optimization iterative process, and post-processing.\n\nThe default parameters indicate the value of the applied concentrated load, the material Young’s modulus, the soft material stiffness, the Poisson ratio, the type of penalization method, the damping factor, and the maximum number of iterations. Fundamentally, the soft material stiffness must be a minimal value larger than zero, and the type of penalization method can be chosen between ‘SIMP’ or ‘RAMP’ for the material interpolation scheme. While the initialization of the design variables step establishes the discretization of the analysis domain by indexing each subvolume, allocating the relative density, and the volume-constrained gradient matrix. Therefore, the design domain is assumed to be rectangular and discretized in rectangular subvolumes. An example of a coarse mesh composed of 12 subvolumes with four edges per subvolume and two degrees of freedom (DOFs) per face is shown in Figure 4.\n\nThe subvolume is indexed row-wise from left to right and down to up, as represented by the bold number shown in Figure 4. Similarly, the subvolume faces are numbered from left to right and down to up, however, the horizontal faces are first indexed, followed by the indexing of the vertical faces, as illustrated in Figure 4. As a result, two DOFs are defined in each subvolume face, where the DOFs 2j−1 and 2j correspond to the horizontal and vertical displacement of face j, respectively. The DOFs assemblage is operated by the subroutine:\n\nwhere dof is the matrix containing the subvolume DOFs, ndof is the total number of DOFs, and ijK is the indexing matrix employed for the global stiffness matrix assemblage.\n\nThe row iK and column jK index vectors are generated by a Kronecker matrix product with a unit vector of 8 lines. The resulting vectors iK and jK are structured so that the iK(i) and jK(j) indices correspond to the assemblage of the stiffness matrix for the subvolume q. The assembly of the global system of equations is performed by employing the sparse function in Matlab, which takes three vectors as input arguments: the first and second contain the row and column indices of the non-zero entries, while the third vector contains the entry values of the sparse vectors and matrices. It can be also suggested the use of the fsparse routine, developed by Engblom and Lukarski (2016), which enhances the sparse assembly by providing a better ordering of the performed operations. Although Ferrari and Sigmund (2020) have achieved a speedup of 170-250% in the algorithm compared to sparse function on a single-core processor, the performance achieved in our computational environment is similar for both routines. The fsparse routine is performed by setting the variable varargin as ‘fast’, while the absence of values for this variable indicates the use of the ‘sparse’ routine.\n\nThe structure supporting conditions are prescribed in supp vector by specifying which DOFs of the discretized domain are fixed, while the natural boundary conditions are specified directly in the global force vector F by addressing the DOFs with prescribed loads and their respective magnitude force values. The assemblage of the global stiffness matrix is operated by the function\n\nfor sK = K0(:)*E(:)’, where K0 is the local stiffness matrix for a unitary elastic modulus obtained with the function\n\nand E is the chosen material interpolation scheme. While the local stiffness matrix is symmetric, rounding errors during the assembly of the global stiffness matrix using the sparse or fsparse commands can cause asymmetry. To correct this, symmetry is enforced at the global level, improving the efficiency of the Matlab backslash (\\) command, as recommended by Andreassen et al. (2011).\n\nAfter solving the global system of equations, the subvolume compliance and its sensitivities are calculated. The objective function value is obtained by adding the individual contribution of each subvolume in the discretized domain, while the subvolume sensitivities are modified considering the aspects of the chosen filtering technique. Subsequently, the design variables are updated by the OC method. The convergence criterium is adopted as 1% of tolerance for the maximum change in design variables. As post-processing step, the investigated numerical aspects are printed, followed by the plotting of the optimized topology. Finally, the processing time is computed for the performed analysis.\n\n\n5. Illustrative examples\n\nThe performed example is a cantilever deep beam subject to a concentrated load, as shown in Figure 5. In this case, the vertical and horizontal averaged displacements at the edges of the left border of the structure are fixed, so the supp vector is set up as\n\nand the concentrated load is positioned in the middle of the right border in the structure, therefore, the global force vector F is given by\n\nThe data initialization is set up as P=−1, for the applied concentrated load, E0=1, for the Young’s modulus, Emin=10−9, for the soft material stiffness, ν=0.3, for the Poisson’s ratio, η=1/2, for the damping factor, move=0.2, for the move-limit, and maxit=100, for the maximum number of iterations. For the approaches using the SIMP model, the damping factor is adjusted to 1/2.6 to avoid the oscillatory phenomenon, as discussed by Araujo et al. (2020a,b). The computational environment in terms of programming language and machine can be defined as Matlab R2023a (64-bits) for Windows 11, accompanied by the Optimization and Parallel Computing toolboxes, and processor of 12th Gen Intel(R) Core (TM) i7-1260P 2.10 GHz, RAM 16.0 GB DDR5.\n\nConsidering the same parameters employed by Araujo et al. (2020a) in the filtering scenario, the algorithm can be started by the following command:\n\nwhich consists in the application of the sensitivity filter considering the adjacent subvolumes with a filter radius of 0.71, given by approximately 1.01lq2+hq2, where lq and hq represent the subvolume dimensions, and a volume fraction of 40% of the total volume. The fsparse routine can be performed by including varargin = ‘fast’ in the Top2DFVT command. The obtained optimized topologies for the SIMP model are shown in Figure 6, where Figure 6a, 6b, and 6c show the optimized topologies obtained by employing the sensitivity, density, and no filtering techniques, respectively. The investigated numerical aspects are presented in Table 1. In general, the obtained optimized topologies have shown to be checkerboard-free and the employed filtering techniques have qualitatively reduced the mesh dependency issue. Araujo et al. (2020a,b) have already verified these features; however, the current algorithm has obtained similar results by reducing the computational cost by 99.8%. For instance, the same analysis performed for a cantilever deep beam using the sensitivity filter with a mesh of 20,402 subvolumes took 10 hours, 28 minutes, and 37 seconds in Araujo et al. (2020a), while the same analysis employing the Top2DFVT algorithm took only 1 minute and 6 seconds, as shown in Table 1.\n\nFor the RAMP approach, the penalty factor variable is adjusted to penal = 0:0.5:3, and the variable model is modified to ‘RAMP’. The optimized topologies obtained for the RAMP model are shown in Figure 7, considering the application of the sensitivity filter, Figure 7a, density filter, Figure 7b, and no filtering, Figure 7c. In general, they are checkerboard-free optimized topologies with a reduction in the obtained structural compliance values compared to the optimized topologies generated by the SIMP model, as presented in Table 1. The no-filter approach generated an optimized structure like the optimized topologies obtained by employing the SIMP model and mesh-independent filters. Thus, the RAMP model coupled with the finite-volume theory has shown to be checkerboard-free and mesh-independent for the cantilever deep beam example, which are desired features for manufacturing purposes. In addition, the sensitivity filter for RAMP model has obtained better results by reducing the optimized structural perimeter even more. Table 1 also presents the investigated numerical aspects for the cantilever deep beam example considering the RAMP model. The approach based on the sensitivity filter has presented the lowest number of iterations and computational cost, while the density filter has shown the highest processing time. The minimum value for structural compliance is observed when the no-filtering technique is employed.\n\nFor computational efficiency, the fsparse routine is also implemented; however, for the performed analyses, such a difference in computational cost does not justify using the fsparse routine. However, a gain in computational performance is observed by around 30% when meshes with size between 105 and 106 subvolumes are employed. From Table 1, the non-filtering approach has obtained the optimized topologies with the minimum compliance. In contrast, the density filter approach has obtained the optimized topologies with the maximum values for compliance. In general, Top2DFVT provides a platform to perform 2D topology optimization of structures in Matlab, starting from a domain initialization for structured meshes to data post-processing. Several computational tools have been proposed for topology optimization employing analysis domains discretized with essential features for finite-element approaches. As previously discussed, the finite-volume theory is an alternative technique to the finite-element method in the context of topology optimization algorithms. In addition, this is the first contribution to offer an algorithm that shows the implementation of standard finite-volume theory for structured meshes problems in Matlab. This investigation employs the finite-volume theory in topology optimization for compliance minimization problems.\n\nTop2DFVT offers some advantages, such as:\n\na) It generates checkerboard-free optimized topologies even when a non-filtering approach is employed.\n\nb) It can be applied to medium and large-scale problems, as the implementation and computational performance are suited to these approaches.\n\nc) It employs different material interpolation methods for topology optimization, such as RAMP and SIMP models. When the non-filtering technique is employed, the optimized topologies generated by the RAMP model usually reduce the perimeter compared to those optimized topologies obtained by the SIMP approach.\n\nThe Top2DFVT algorithm is currently being employed for educational and research purposes to promote the advantages of the finite-volume theory in the numerical analysis of structures.\n\n\n6. Numerical results\n\nIn this contribution, three examples are analyzed employing the compliance minimization problem based on the finite-volume theory for linear elastic materials under plane stress state, where the RAMP and SIMP approaches are employed to interpolate the material stiffness. The investigated examples are a cantilever beam subjected to a concentrated load, a Messerschmitt-Bölkow-Blom (MBB) beam, and an L-bracket beam subject to a concentrated load. Some numerical aspects are also investigated during the analyses, such as the number of iterations, processing time, and compliance estimation. The continued penalization scheme is adopted for the compliance minimization problem, where the penalty factor increases gradually (∆p=0.25) from 1 to 4 for SIMP and from 0 to 3 for RAMP. A maximum of 200 iterations is assumed for each performed penalty factor along the optimization process.\n\nA classical problem in topology optimization is the cantilever deep beam, whose analysis domain and boundary conditions are illustrated in Figure 8. In this example, it is observed a region of stress concentration where the concentrated load is applied. The adopted geometrical and physical parameters can be described as H=450 mm, L=900 mm, d=10 mm, P=1000 N, E=200 GPa (Young Modulus), and ν=0.3 (Poisson’s ratio). The proposed optimization problem consists of minimizing the structural compliance, with a volume constraint of 40% of the total volume.\n\nFigure 9 shows the obtained optimized topologies for the approach based on the finite-volume theory considering the SIMP material interpolation method, while Table 2 presents the investigated numerical parameters for each performed analysis. Although the non-filtering approach has obtained the lowest value for the objective function, the sensitivity filter results have presented the lowest computational cost and optimized topologies that better controls the length scale issue, by reducing the formation of thin bars. The density filtering results have shown more thin bars in the optimized topologies when compared to the sensitivity filter, and higher values for the compliance function in the overall investigation. For the SIMP method and considering the non-filtering strategies, the damping factor is adjusted to 1/2.6 to avoid divergence during the optimization process.\n\nFigure 10 shows the obtained optimized topologies for the approach based on the RAMP method. In general, the RAMP method has obtained checkerboard-free optimized topologies by reducing the structural perimeter when the non-filtering strategy is employed in comparison to the same approach employing the SIMP approach, which is a desired feature for manufacturing purposes. On the other hand, the optimized topologies obtained by the SIMP method usually present a higher structural perimeter by producing more thin bars. Additionally, the RAMP method has obtained a well-defined black-and-white design with lower values for the compliance function, as presented in Table 2.\n\nTable 2 presents the numerical aspects of the performed investigations for the cantilever deep beam example. In general, the RAMP method has presented a higher number of iterations and processing time, although the obtained optimized topologies have presented the lowest values for the objective function. The filter radius is calculated to be slightly higher than 1.01lq2+hq2 for the coarse mesh. Therefore, the optimized topology obtained for the finest mesh employing the sensitivity filter is very similar to that obtained for the coarse mesh without filtering techniques. This is only possible because the finite-volume theory is a checkerboard-free numerical technique in topology optimization algorithms.\n\nOther classical problem for topology optimization of continuum structures is the Messerschmitt-Bölkow-Blom (MBB) beam. In this case, only half of the structure is analyzed as shown on Figure 11, where the geometric and physical parameters are taken as H=300 mm, L=900 mm, d=10 mm, P=1000 N, E=78 GPa (Young Modulus), and ν=0.25 (Poisson’s ratio). The volume fraction for the minimum compliance optimization problem is assumed as 40% of the total structure volume.\n\nFigure 12 shows the optimized topologies obtained considering the application of the SIMP method, while Table 3 presents the investigated numerical aspects for each performed analysis. The topology optimization technique considers the non-filtering, sensitivity, and density filtering scenarios. The adopted filter radius is slightly higher than half of the subvolume’s diagonal length for the coarsest mesh, which can be written as 1.01lq2+hq2 and approximated by 15 mm. The no-filter analysis generally generates topologies with more thin bars, while the sensitivity filter obtains cleaner topologies with a reduced structural perimeter. Besides, the density filter has not presented the same efficiency as the sensitivity filter in reducing the structural perimeter in the final optimized topology, and the obtained compliance is higher when compared to the other approaches. Regarding computational cost, the sensitivity filter approach obtained the lowest processing time and number of iterations, while the density filter approach presented the highest processing time and number of iterations.\n\nFigure 13 shows the optimized topologies for the analyses employing the RAMP method, where the adopted filter radius is the same as those employing the SIMP method. The RAMP method has generally obtained optimized topologies with better control of the structural perimeter, even when the non-filtering technique is employed. Additionally, the optimized topology obtained for the coarse mesh without filtering techniques is geometrically close to the optimized topologies for the finest mesh employing filtering strategies. Therefore, the results obtained for the coarse mesh in the no-filter strategy employing the RAMP method could be adopted as the solution for the optimization problem. Table 3 presents the investigated numerical aspects, where the number of iterations and processing time are usually higher for this method when compared to the SIMP approach.\n\nAnother analyzed topology optimization problem for stress concentration in two-dimensional structures is the L-bracket beam, whose analysis domain and boundary conditions are illustrated in Figure 14. In the L-bracket beam problem, it is observed a high level of stress concentration in the corner, which is important to check how the new Top2DFVT code leads to these kinds of topology optimization problems. The employed geometric parameters for this beam are assumed as d=5 cm, L=100 cm, and P=200 kN, while the adopted material properties are E=70 GPa (elastic moduli) and ν=0.25 (Poisson’s ratio). The proposed optimization problem consists of minimizing the structural compliance function under a volume constraint of 40% of the total volume.\n\nFigure 15 shows the optimized topologies obtained by the SIMP approach for the L-bracket beam problem, considering the absence of filtering techniques and the implementation of the sensitivity and density filters, respectively. The sensitivity filter has reduced the formation of thin bars along the optimized topologies, while the density filter has obtained irregular optimized topologies with the appearance of substantial gray regions. On the other hand, the no-filter strategy has generated well-defined optimized topologies with more thin bars, especially when compared to the sensitivity filter strategy. As Araujo et al. (2020a) suggested, the damping factor is adjusted to 1/2.6 for all performed approaches employing the SIMP to guarantee the absence of the oscillatory phenomenon to any employed filter radius. Table 4 presents the investigated numerical aspects for the performed analyses employing the SIMP method.\n\nFigure 16 presents the obtained optimized topologies by the RAMP method for the L-bracket beam problem. The RAMP method has generally reduced the formation of thin bars, demonstrating less sensitivity with the adopted meshes. As in the SIMP method, the sensitivity filter has shown to be more efficient by reducing the formation of thin bars in the optimized topologies, and the density filter has obtained more irregular topologies with the presence of gray regions. The RAMP method is more stable numerically, and the adopted damping factor is 1/2, which guarantees a faster convergence for the analyses. However, the number of iterations is usually higher for the RAMP method.\n\nTable 4 presents the investigated numerical aspects of the optimized structures, such as the total number of iterations, processing time, and compliance estimation. When the sensitivity filter is employed, there is a remarkable decrease in the number of iterations and computational costs. However, the obtained values for structural compliance are lower when the non-filtering strategy is performed. In general, the RAMP method has been shown to efficiently produce checkerboard-free optimized topologies with lower values for structural compliance. Thus, these results demonstrate the proposed approach’s efficiency and justify its use in topology optimization problems of continuum elastic structures since it better controls numerical issues associated with checkerboard and length scale. The filter radius is slightly higher than 1.01lq2+hq2 for the coarse mesh. As a result, the filter guarantees the absence of mesh dependency, especially when the RAMP method or the sensitivity filter are employed.\n\n\n7. Conclusions\n\nThis study introduces the Top2DFVT, an innovative Matlab algorithm tailored for the topology optimization of two-dimensional elastic structures via the finite-volume theory. This contribution addresses compliance minimization problems, presenting a checkerboard-free methodology that mitigates numerical instabilities like mesh dependence and local minima, commonly encountered in gradient-based optimization techniques. The algorithm showcases improved computational efficiency and the ability to generate optimized topologies for medium to large-scale problems by employing two material interpolation schemes, SIMP and RAMP, alongside sensitivity and density filters. Such advancements facilitate the design of high-performance structures with potential applications in various engineering domains.\n\nThis algorithm can provide checkerboard-free optimized topologies and reduce mesh dependence or length scale issues, mainly when the RAMP method is employed. The optimized topologies obtained without filtering techniques for the coarse meshes and employing the RAMP method are similar to those obtained with filtering strategies for the finer meshes. Usually, filtering techniques are based on image processing that geometrically changes the sensitivity or the relative density values. Therefore, obtaining optimized structures without filtering techniques provides more reliable and efficient designs. Besides, the optimized topologies without filtering strategies are well-defined “black and white” designs, where intermediate values of relative densities are reduced.\n\nThe approach based on the finite-volume theory is also performed by employing a sensitivity filter to solve problems related to mesh dependence and length scale issues. The adopted strategy to define the filter radius consists of using approximately the subvolume’s or element’s diagonal of the coarse mesh. The continued penalization scheme is adopted for the compliance minimization problem, which guarantees a gradual convergence for the overall process. When the SIMP method is employed, the OC method’s damping factor can be adjusted to 1/2.6 to avoid divergence during the optimization process, especially when non-filtering strategies are employed.\n\nIn conclusion, this study presents a novel approach to topology optimization using the finite-volume theory and significantly contributes to the field by addressing and overcoming inherent numerical challenges. The Top2DFVT algorithm represents a pivotal advancement in optimizing elastic structures, promising more reliable and efficient design solutions. The authors’ efforts in developing and sharing this tool underscore the collaborative spirit of the research community, aiming to broaden the understanding and application of topology optimization in engineering.\n\nThis work sets a new benchmark for future research, encouraging further exploration and development of optimization techniques. By providing a robust and efficient tool in Top2DFVT, the authors offer valuable resources for educators, researchers, and practitioners alike, fostering innovation and excellence in engineering design.\n\nEthical approval and consent were not required.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgements\n\nThe authors acknowledge the financial support provided by the National Council for Scientific and Technological Development (CNPq), Coordination for the Improvement of Higher Education Personnel (CAPES), and Alagoas State Research Support Foundation (FAPEAL).\n\n\nReferences\n\nAage N, Andreassen E, Lazarov BS: Topology optimization using PETSc: An easy-to-use, fully parallel, open-source topology optimization framework. Struct. Multidiscip. Optim. 2015; 51: 565–572. Publisher Full Text\n\nAage N, Jørgensen MN, Andreasen CS, et al.: Interactive topology optimization on hand-held devices. Struct. Multidiscip. Optim. 2013; 47: 1–6. Publisher Full Text\n\nAage N, Lazarov BS: Parallel framework for topology optimization using the method of moving asymptotes. Struct. Multidiscip. Optim. 2013; 47: 493–505. 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Publisher Full Text\n\nBouajila W, Furusawa D, Shimoda M: Multidisciplinary free-form optimization of solid structures for mean compliance minimization and time-dependent temperature control. Struct. Multidiscip. Optim. 2021; 63(5): 2305–2324. Publisher Full Text\n\nCavalcante MAA, Marques SPC, Pindera M-J: Parametric formulation of the finite-volume theory for functionally graded materials – Part I: analysis. J. Appl. Mech. 2007a; 74(5): 935–945. Publisher Full Text\n\nCavalcante MAA, Marques SPC, Pindera M-J: Parametric formulation of the finite-volume theory for functionally graded materials – Part II: numerical results. J. Appl. Mech. 2007b; 74(5): 946–957. Publisher Full Text\n\nCavalcante MAA, Marques SPC, Pindera M-J: Computational aspects of the parametric finite-volume theory for functionally graded materials. Comput. Mater. Sci. 2008; 44(2): 422–438. Publisher Full Text\n\nCavalcante MAA, Pindera M-J: Generalized finite-volume theory for elastic analysis in solid mechanics – part I: framework. J. Appl. Mech. 2012a; 79(5): 051006. Publisher Full Text\n\nCavalcante MAA, Pindera M-J: Generalized finite-volume theory for elastic analysis in solid mechanics – part II: results. J. Appl. Mech. 2012b; 79(5): 051007. Publisher Full Text\n\nDeaton JD, Grandhi RV: A survey of structural and multidisciplinary continuum topology optimization: post 2000. Struct. Multidiscip. Optim. 2014; 49: 1–38. Publisher Full Text\n\nEngblom S, Lukarski D: Fast Matlab compatible sparse assembly on multicore computers. Parallel Comput. 2016; 56: 1–17. Publisher Full Text\n\nFerrari F, Sigmund O: A new generation 99 line Matlab code for compliance topology optimization and its extension to 3D. Struct. Multidiscip. Optim. 2020; 62(4): 2211–2228. Publisher Full Text\n\nKumar P: HoneyTop90: A 90-line Matlab code for topology optimization using honeycomb tessellation. Optim. Eng. 2023; 24: 1433–1460. Publisher Full Text\n\nLee S, Lieu QX, Vo TP, et al.: Topology optimization using super-resolution image reconstruction methods. Adv. Eng. Softw. 2023; 177: 103413. Publisher Full Text\n\nLiu K, Tovar A: An efficient 3D topology optimization code written in Matlab. Struct. Multidiscip. Optim. 2014; 50: 1175–1196. Publisher Full Text\n\nLiu Y, Lai Z, Lu Y, et al.: Topology optimization of shell-infill structures considering buckling constraint. Comput. Struct. 2023; 283: 107055. Publisher Full Text\n\nLiu Z, Korvink JG, Huang I: Structure topology optimization: fully coupled level set method via FEMLAB. Struct. Multidiscip. Optim. 2005; 29(29): 407–417. Publisher Full Text\n\nMa Z-D, Kikuchi N, Hagiwara I: Structural topology and shape optimization for a frequency response problem. Comput. Mech. 1993; 13(3): 157–174. Publisher Full Text\n\nMichell AGM: The limits of economy of material in frame structures. The London, Edinburg, and Dublin Philosophical Magazine and Journal of Science. 1904; 8(47): 589–597. Publisher Full Text\n\nMontes MA: Topology optimization algorithms for the solution of compliance and volume problems in 2D. Mexico: Investigation Center in Mathematics; 2016. Master Thesis.\n\nRozvany GIN: A critical review of established methods of structural topology optimization. Struct. Multidiscip. Optim. 2009; 37(3): 217–237. Publisher Full Text\n\nSigmund O: A 99 line topology optimization code written in Matlab. Struct. Multidiscip. Optim. 2001; 21(2): 120–127. Publisher Full Text\n\nSigmund O: Morphology-based black and white filters for topology optimization. Struct. Multidiscip. Optim. 2007; 33(4-5): 401–424. Publisher Full Text\n\nSmit T, Aage N, Ferguson SJ, et al.: Topology optimization using PETSc: a Python wrapper and extended functionality. Struct. Multidiscip. Optim. 2021; 64: 4343–4353. Publisher Full Text\n\nSokół T: A 99 line code for discretized Michell truss optimization written in Mathematica. Struct. Multidiscip. Optim. 2011; 43(2): 181–190. Publisher Full Text\n\nStolpe M, Svanberg K: An alternative interpolation scheme for minimum compliance topology optimization. Struct. Multidiscip. Optim. 2001; 22(2): 116–124. Publisher Full Text\n\nStutz FC, Olsen TF, Groen JP, et al.: Synthesis of frame field-aligned multi-laminar structures. ACM Trans. Graph. 2022; 41(5): 1–20. Publisher Full Text\n\nTalischi C, Paulino GH, Pereira A, et al.: PolyTop: a Matlab implementation of a general topology optimization framework using unstructured polygonal finite-element meshes. Struct. Multidiscip. Optim. 2012; 45: 329–357. Publisher Full Text\n\nTavakoli R, Mohseni SM: Alternating active-phase algorithm for multimaterial topology optimization problems: a 115-line Matlab implementation. Struct. Multidiscip. Optim. 2014; 49: 621–642. Publisher Full Text\n\nWei P, Li Z, Li X, et al.: An 88-line Matlab code for the parameterized level set method based topology optimization using radial basis functions. Struct. Multidiscip. Optim. 2018; 58: 831–849. Publisher Full Text\n\nYi B, Yoon GH, Zheng R, et al.: A unified material interpolation for topology optimization of multi-materials. Comput. Struct. 2023; 282: 107041. Publisher Full Text\n\nZegard T, Paulino GH: GRAND — Ground structure-based topology optimization for arbitrary 2D domains using Matlab. Struct. Multidiscip. Optim. 2014; 50: 861–882. Publisher Full Text\n\nZhou M, Sigmund O: Complementary lecture notes for teaching the 99/88-line topology optimization codes. Struct. Multidiscip. Optim. 2021; 64: 3227–3231. Publisher Full Text\n\nZhuang Z, Xie YM, Li Q, et al.: A 172-line Matlab code for structural topology optimization in the body-fitted mesh. Struct. Multidiscip. Optim. 2023; 66: 11. Publisher Full Text"
}
|
[
{
"id": "306477",
"date": "12 Aug 2024",
"name": "Yingjun Wang",
"expertise": [
"Reviewer Expertise topology optimization"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis paper presents a Matlab implementation for 2D topology optimization based on finite-volume method. The Matlab code Top2DFVT uses the loop vectorization and memory preallocation of top88, which is much more efficient than the authors' previous work. Three examples are tested to demonstrate the validity and efficiency of Top2DFVT. However, there are still some comments for the authors.\n1. How to calculate the local stiffness matrix for a subvolume q should be given.\n2. What is the meaning of the subscripts \"pu\", \"pp\", \"uu\", \"up\" in Eq.(13).\n3. In Section 3.1, there are two cases for the objective function gradient. Is only one of the cases in a subvolume, or the two cases can exist together in a subvolume?\n\n4. In Section 4, an algorithm flowchart of Top2DFVT should be added.\n\n5. In Top2DFVT, the memory preallocation accelerates the computational efficiency, but increases the memory usage. The authors should state this in the paper.\n6. For the illustrative example in Figure 5, why are the number of subvolumes in the horizontal and vertical directions set to 202 and 101, not 200 and 100?\n\n7. In Tables 2-4, it can be found that the number of iterations of No filter cases is larger than the Sensitivity filter cases for the same mesh size, why? In addition, the number of iterations is more than 1000 when the number of elements increases, which is too many for the compliance minimization problem. The convergence history should be given for at least one example.\n8. The proposed method should be compared with finite-element-based topology optimization methods such as top88 or top99neo in detail to demonstrate its validity and efficiency.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nYes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12622",
"date": "22 Oct 2024",
"name": "Marcio Cavalcante",
"role": "Author Response",
"response": "The authors have many thanks to the reviewer for their valuable comments. The manuscript has been revised in accordance with the comments, and detailed revisions are listed below point by point. Comments to the Authors: This paper presents a Matlab implementation for 2D topology optimization based on finite-volume method. The Matlab code Top2DFVT uses the loop vectorization and memory preallocation of top88, which is much more efficient than the authors' previous work. Three examples are tested to demonstrate the validity and efficiency of Top2DFVT. However, there are still some comments for the authors. 1) How to calculate the local stiffness matrix for a subvolume q should be given. Response: As mentioned in the manuscript, the local stiffness matrix calculation can be found in Araujo et al. (2020a).2) 2) What is the meaning of the subscripts \"pu\", \"pp\", \"uu\", \"up\" in Eq.(13). Response: The following description of the submatrices in Eq. (13) was incorporated into the text: The subscripts in Eq. (13) reflect the relationship between prescribed and unknown quantities, where the first index refers to forces and the second to displacements. The letter \"u\" denotes unknown quantities, while \"p\" represents prescribed ones. Therefore, the submatrix Kpu expresses the coupling between prescribed forces and unknown displacements, while Kpp defines the relationship between prescribed forces and prescribed displacements. Similarly, Kup describes the interaction between unknown forces and prescribed displacements, and Kuu corresponds to the relationship between unknown forces and unknown displacements. This indexing scheme distinguishes between the interactions of prescribed and unknown quantities within the stiffness matrix. 3) In Section 3.1, there are two cases for the objective function gradient. Is only one of the cases in a subvolume, or the two cases can exist together in a subvolume? Response: The two cases mentioned in section 3.1 refer to the global system of equations that relates the global force vector with the global displacement vector. The following text was added to the manuscript to clarify the case used in the analyzed examples: The examples analyzed in the following sections are associated with the second case, where a prescribed force is applied, and all the prescribed displacements are zero. 4) In Section 4, an algorithm flowchart of Top2DFVT should be added. Response: The authors agreed with the reviewer, and the following flowchart was added to the manuscript. Figure 4. Flowchart of the Top2DFVT for the topology optimization of linear elastic continuum structures. 5) In Top2DFVT, the memory preallocation accelerates the computational efficiency, but increases the memory usage. The authors should state this in the paper. Response: The authors agreed with the reviewer, and the following text was added to the manuscript: In the Top2DFVT implementation, memory preallocation is crucial in enhancing computational efficiency by reducing the time required for matrix assembly and solving linear systems. However, this performance gain comes at the expense of increased memory usage, as large data structures must be allocated in advance. This trade-off between computational speed and memory consumption is a common consideration in the design of topology optimization algorithms. While the memory overhead is manageable for medium-sized problems, it can become significant for large-scale applications. Therefore, careful management of memory resources is essential to balance efficiency and scalability. 6) For the illustrative example in Figure 5, why are the number of subvolumes in the horizontal and vertical directions set to 202 and 101, not 200 and 100? Response: The following text was added to the manuscript: In this example, the dimensions of the cantilever deep beam are L=100 and H=50, and the concentrated load is applied at the center of the free edge. To ensure the load is applied to the face of a single subvolume, the number of subvolumes in the vertical direction must be odd. Furthermore, to generate an analysis domain with square subvolumes, the number of subvolumes in the horizontal direction must be twice the number of those in the vertical direction. 7) In Tables 2-4, it can be found that the number of iterations of No filter cases is larger than the Sensitivity filter cases for the same mesh size, why? In addition, the number of iterations is more than 1000 when the number of elements increases, which is too many for the compliance minimization problem. The convergence history should be given for at least one example. Response: The following text and figure were added to the manuscript: Adopting the continued penalization scheme, combined with a highly restrictive local convergence criterion, increases the number of iterations in the investigated examples, especially for the most refined meshes, where achieving local convergence is more challenging. The smooth local response produced by the sensitivity filter accelerates convergence compared to the optimization process without filtering techniques, a result not observed with the density filter. Figure 9 displays the objective function histories throughout the optimization process of the cantilever deep beam for the SIMP and RAMP methods, highlighting that the density filter demands more iterations for convergence. In contrast, the optimization process with the sensitivity filter achieves the fastest convergence. The RAMP method provides closer values for the objective function throughout the optimization process for the three approaches adopted: results without filters, with the sensitivity filter, and with the density filter. Furthermore, the RAMP method demonstrates a more stable convergence process than the SIMP method for these approaches. Notably, the jumps in the continued penalization scheme are significantly smaller for the RAMP method than those between different penalty factors in the SIMP method. Figure 9. Objective function histories for the SIMP and RAMP methods. 8) The proposed method should be compared with finite-element-based topology optimization methods such as top88 or top99neo in detail to demonstrate its validity and efficiency. Response: The authors agreed with the reviewer, and the following texts and figures were added to the manuscript: The algorithm known as top99neo, proposed by Ferrari and Sigmund in 2020, is used as a benchmark source for the traditional finite-element method for bilinear elements. The algorithm uses the continued penalization scheme, gradually increasing the penalty factor (∆p=0.25) from 1 to 4, similar to the finite-volume theory approach. Each penalty factor is subjected to 25 iterations. The Heaviside projection parameters are updated throughout the optimization process. The parameter β starts at 2 and increases to 16 by an increment of ∆β=2 every 25 iterations. Figure 12 shows the optimized topologies obtained using the density filter. The filter radius changes to reflect the exact size of the filter radius employed in the finite-volume theory approaches for each mesh size (1.5, 3, and 6, respectively). The optimized topologies obtained using the finite-element approach are more mesh-dependent, even when filtering strategies are employed, as compared to the optimized topologies obtained using the finite-volume theory approach, especially in the case of the results with the sensitivity filter. The computational cost for the finest mesh is 2 minutes and 30 seconds, with a maximum of 350 iterations. The total number of degrees of freedom for the finite-element approach is 132132, while the finite-volume theory approach has a total of 260280 degrees of freedom, which partially explains the difference in computational costs. As the top99neo algorithm employs finite elements with unitary dimensions, it is not feasible to compare the obtained values for the objective function of the optimized topologies. Figure 12. Optimized topologies for the cantilever deep beam employing the top99neo algorithm. Figure 16 shows the optimized topologies obtained employing the top99neo algorithm, where the penalty factor increases gradually (∆p=0.25) from 1 to 4 after every 25 iterations until a maximum of 350 iterations, and the beta parameter increases gradually from 2 to 16 (∆β=2), after every 25 iterations, similarly to the cantilever deep beam example. The optimized topologies shown in Figure 16 are mesh dependents even when filtering strategies are employed. The filter radius is assumed to be 1.5 for the 90x30 mesh, 3 for the 180x60 mesh, and 6 for the 360x120 mesh. When a similar filter radius is employed in the context of the finite-volume theory, this technique demonstrates a less mesh sensitivity behavior when compared to finite element-based strategies. Regarding computational efficiency, the top99neo code has presented a processing time of 86 seconds for the finest mesh. Generally, the Top2DFVT algorithm presents a higher computational cost when compared to the Q4 finite element-based algorithm. The number of degrees of freedom partially explains this higher computational cost once the total number of degrees of freedom for the finest mesh considering the top99neo algorithm is 87362, while in the Top2DFVT algorithm, the total number of degrees of freedom for the same analysis is 173760. Furthermore, the number of iterations for this example is relatively high for the finite-volume theory approaches once the top99neo algorithm adopts a maximum of 350 iterations. Figure 16. Optimized topologies for the MBB beam employing the top99neo algorithm. The top99neo algorithm is also performed considering the L-bracket beam problem, and the obtained optimized topologies can be observed in Figure 20. As in the previous examples, the same numerical parameters are employed for the physical model, such as the gradual increase in the penalty factor, from 1 to 4 with ∆p=0.25, and in the Heaviside Projection β parameter, from 2 to 16 with ∆β=2. In terms of computational cost, the top99neo code has presented a processing time of 1 minute and 1 second for the finest mesh, considering a total of 350 iterations, while the Top2DFVT algorithm has presented a processing time of 39 seconds with a total of 155 iterations for of the SIMP method and the sensitivity filter. This difference in processing time can be partially explained by the difference in the total number of iterations observed during the topology optimization analyses. For this example, the Top2DFVT algorithm, considering the sensitivity filter approach, presents a reduced number of iterations for convergence. Figure 20. Optimized topologies for the L-bracket beam employing the top99neo algorithm."
}
]
},
{
"id": "313232",
"date": "26 Aug 2024",
"name": "Minh Ngoc Nguyen",
"expertise": [
"Reviewer Expertise Topology optimization"
],
"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 for Top2DFVT: An efficient Matlab Implementation for topology optimization based on Finite-Volume theory\n\nThe manuscript presents a Matlab implementation for topology optimization based on Finite Volume theory for 2D compliance problems. In general, the manuscript is interesting and is very useful for beginners of topology optimization. The Matlab code is fast, due to vectorization and memory pre-allocation, in a manner similar to the code top88 (Andreassen E, et al., 2011 [Ref 1]). Compared to the previous works by the same group of authors, computational time is reduced significantly. However, there are many unclear information that needs thorough revision by the authors 1. Although the approach may not require filter to avoid checkerboard pattern, it is clearly observed in the results that when no filter is applied, many thin components appear in the optimized design. Such thin components may be suffered from high stress values. In fact, as in the literature, filter also contributes to length-scale control. The authors should discuss this aspect. 2. When there is no filter, it seems that clear “black and white” results could be obtained. Nevertheless, the authors should compute the non-discreteness values to quantitatively demonstrate this aspect. On the other hand, when filter (either sensitivity filter or density filter) is applied, gray elements appear. In order to reduce the gray elements and increase the discreteness of the solution, volume-preserving Heaviside projection is commonly employed. The authors should also mention this.\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": "12623",
"date": "22 Oct 2024",
"name": "Marcio Cavalcante",
"role": "Author Response",
"response": "The authors have many thanks to the reviewer for their valuable comments. The manuscript has been revised in accordance with the comments, and detailed revisions are listed below point by point. Comments to the Authors: Reviewer comment: The manuscript presents a Matlab implementation for topology optimization based on Finite Volume theory for 2D compliance problems. In general, the manuscript is interesting and is very useful for beginners of topology optimization. The Matlab code is fast, due to vectorization and memory pre-allocation, in a manner similar to the code top88 (Andreassen E, et al., 2011 [Ref 1]). Compared to the previous works by the same group of authors, computational time is reduced significantly. However, there are many unclear information that needs thorough revision by the authors. 1) Although the approach may not require filter to avoid checkerboard pattern, it is clearly observed in the results that when no filter is applied, many thin components appear in the optimized design. Such thin components may be suffered from high stress values. In fact, as in the literature, filter also contributes to length-scale control. The authors should discuss this aspect. Author response: The authors agreed with the reviewer, and the following texts were added to the manuscript: Although the finite-volume theory employed in the TOP2DFVT algorithm effectively mitigates checkerboard patterns, filtering techniques remain essential for producing manufacturable designs. Filters such as sensitivity and density filters play a crucial role in controlling the characteristic length scale, thereby reducing the formation of thin structural elements that could cause fabrication and structural stability challenges. Additionally, applying these filters contributes to a smoother distribution of material, resulting in a more uniform stress distribution across the structure. However, results obtained without filters can also be explored effectively within the finite-volume theory framework. When working with coarser meshes, the larger subvolumes naturally limit the appearance of thin elements, which helps to define a more favorable topology from a manufacturing perspective. These larger subvolumes act as a resolution control mechanism, preventing the appearance of fine bars that could lead to structural issues such as localized buckling or stress concentration. Thus, the finite-volume theory provides a flexible approach for generating optimized topologies that balance manufacturability and structural robustness by carefully selecting the mesh size and employing or omitting filters as appropriate. Reviewer comment: 2) When there is no filter, it seems that clear “black and white” results could be obtained. Nevertheless, the authors should compute the non-discreteness values to quantitatively demonstrate this aspect. On the other hand, when filter (either sensitivity filter or density filter) is applied, gray elements appear. In order to reduce the gray elements and increase the discreteness of the solution, volume-preserving Heaviside projection is commonly employed. The authors should also mention this. Author response: The authors agreed with the reviewer, and the following texts were added to the manuscript: In topology optimization without filters, distinct \"black and white\" designs can typically be achieved, representing clear material and void regions. When filters such as sensitivity or density filters are applied, gray regions often emerge in the design. These gray elements represent intermediate density values that compromise the binary nature of the solution. To mitigate this issue and increase the discreteness of the topology, volume-preserving Heaviside projection is a commonly used strategy. The Heaviside projection function sharpens the transition between material and void by pushing intermediate densities towards 0 or 1, thereby reducing the gray regions. This technique preserves the total volume while enhancing the manufacturability of the optimized structure (Bendsøe and Sigmund 2003; Ferrari and Sigmund 2020). Future implementations of the proposed method could benefit from incorporating the Heaviside projection to refine the design’s discreteness further and improve its practical applicability in manufacturing processes, especially when employing filtering techniques."
}
]
},
{
"id": "313235",
"date": "04 Sep 2024",
"name": "Volnei Tita",
"expertise": [
"Reviewer Expertise Computational Analysis of Composite Structures"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe paper consists of providing a MATLAB code based on Finite-Volume Theory (named Top2DFVT), which can perform 2D topology optimization of structures by using SIMP and RAMP algorithms. On one hand, the manuscript brings relevant results, mitigating some numerical instabilities, such as checkerboard and mesh dependence issues. By another hand, there are some important aspects related to the manuscript and to the implemented code, which need to be better clarified by the authors as follows: (*) 1. Introduction - The authors claim that “…this is the first time a platform for optimizing structures using the finite-volume theory…”. It is very hard to confirm that there is not any work in the World previously published in a journal or conference in this field. Thus, it is recommended that the authors modify the text by the inclusion of “Based on the authors’ knowledge, this is the first time a platform…”. - The authors mentioned about computational cost, comparing the previous version of the code approached in Araujo et al. (2020a) with the present one. However, it would be very important to compare and discuss advantages and disadvantages with other codes. For example, usually, FORTRAN codes run faster than MALTAB codes. In fact, in the final of Section 5, the authors presented some advantages, but it is not possible to find drawbacks. (*) 2. Finite-volume theory - In the Eq (4), K is a non-symmetric matrix, then the computational cost of topology optimization based on the FVT is higher than based on the FEM. The authors should comment quantitative values, expressing how slow is the process based on the FVT. (*) 6. Numerical results - The authors analyzed 3 Case Studies (cantilever deep beam; half MBB beam; L-bracket beam) to show the potentialities of the developed MATLAB code. But they are invited to analyze one of the case studies presented in the paper cited below: A concurrent fibre orientation and topology optimisation framework for 3D-printed fibre-reinforced composites - (Almeida Jr. J, et al., 2023 [Ref 1]) In other words, they should compare the results obtained by the Top2DFVT with the results discussed in the 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?\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": "12624",
"date": "22 Oct 2024",
"name": "Marcio Cavalcante",
"role": "Author Response",
"response": "The authors have many thanks to the reviewer for their valuable comments. The manuscript has been revised in accordance with the comments, and detailed revisions are listed below point by point. Comments to the Authors: The paper consists of providing a MATLAB code based on Finite-Volume Theory (named Top2DFVT), which can perform 2D topology optimization of structures by using SIMP and RAMP algorithms. On one hand, the manuscript brings relevant results, mitigating some numerical instabilities, such as checkerboard and mesh dependence issues. By another hand, there are some important aspects related to the manuscript and to the implemented code, which need to be better clarified by the authors as follows: 1) Introduction - The authors claim that “…this is the first time a platform for optimizing structures using the finite-volume theory…”. It is very hard to confirm that there is not any work in the World previously published in a journal or conference in this field. Thus, it is recommended that the authors modify the text by the inclusion of “Based on the authors’ knowledge, this is the first time a platform…”. Response: The authors agreed with the reviewer, and the following modification was made to the manuscript: In addition, based on the authors’ knowledge, this is the first time a platform for optimizing structures using the finite-volume theory can be applied to medium and large-scale problems, besides obtaining checkerboard-free and mesh-independent designs. 1) Introduction - The authors mentioned about computational cost, comparing the previous version of the code approached in Araujo et al. (2020a) with the present one. However, it would be very important to compare and discuss advantages and disadvantages with other codes. For example, usually, FORTRAN codes run faster than MALTAB codes. In fact, in the final of Section 5, the authors presented some advantages, but it is not possible to find drawbacks. Response: The authors agreed with the reviewer, and the following texts and figures were added to the manuscript with results obtained by the top99neo algorithm, discussing the advantages and disadvantages of the Top2DFVT code: The algorithm known as top99neo, proposed by Ferrari and Sigmund in 2020, is used as a benchmark source for the traditional finite-element method for bilinear elements. The algorithm uses the continued penalization scheme, gradually increasing the penalty factor (∆p=0.25) from 1 to 4, similar to the finite-volume theory approach. Each penalty factor is subjected to 25 iterations. The Heaviside projection parameters are updated throughout the optimization process. The parameter β starts at 2 and increases to 16 by an increment of ∆β=2 every 25 iterations. Figure 12 shows the optimized topologies obtained using the density filter. The filter radius changes to reflect the exact size of the filter radius employed in the finite-volume theory approaches for each mesh size (1.5, 3, and 6, respectively). The optimized topologies obtained using the finite-element approach are more mesh-dependent, even when filtering strategies are employed, as compared to the optimized topologies obtained using the finite-volume theory approach, especially in the case of the results with the sensitivity filter. The computational cost for the finest mesh is 2 minutes and 30 seconds, with a maximum of 350 iterations. The total number of degrees of freedom for the finite-element approach is 132132, while the finite-volume theory approach has a total of 260280 degrees of freedom, which partially explains the difference in computational costs. As the top99neo algorithm employs finite elements with unitary dimensions, it is not feasible to compare the obtained values for the objective function of the optimized topologies. See Figure 12. Optimized topologies for the cantilever deep beam employing the top99neo algorithm.(URL) Figure 16 shows the optimized topologies obtained employing the top99neo algorithm, where the penalty factor increases gradually (∆p=0.25) from 1 to 4 after every 25 iterations until a maximum of 350 iterations, and the beta parameter increases gradually from 2 to 16 (∆β=2), after every 25 iterations, similarly to the cantilever deep beam example. The optimized topologies shown in Figure 16 are mesh dependents even when filtering strategies are employed. The filter radius is assumed to be 1.5 for the 90x30 mesh, 3 for the 180x60 mesh, and 6 for the 360x120 mesh. When a similar filter radius is employed in the context of the finite-volume theory, this technique demonstrates a less mesh sensitivity behavior when compared to finite element-based strategies. Regarding computational efficiency, the top99neo code has presented a processing time of 86 seconds for the finest mesh. Generally, the Top2DFVT algorithm presents a higher computational cost when compared to the Q4 finite element-based algorithm. The number of degrees of freedom partially explains this higher computational cost once the total number of degrees of freedom for the finest mesh considering the top99neo algorithm is 87362, while in the Top2DFVT algorithm, the total number of degrees of freedom for the same analysis is 173760. Furthermore, the number of iterations for this example is relatively high for the finite-volume theory approaches once the top99neo algorithm adopts a maximum of 350 iterations. See Figure 16. Optimized topologies for the MBB beam employing the top99neo algorithm.(URL) The top99neo algorithm is also performed considering the L-bracket beam problem, and the obtained optimized topologies can be observed in Figure 20. As in the previous examples, the same numerical parameters are employed for the physical model, such as the gradual increase in the penalty factor, from 1 to 4 with ∆p=0.25, and in the Heaviside Projection β parameter, from 2 to 16 with ∆β=2. In terms of computational cost, the top99neo code has presented a processing time of 1 minute and 1 second for the finest mesh, considering a total of 350 iterations, while the Top2DFVT algorithm has presented a processing time of 39 seconds with a total of 155 iterations for of the SIMP method and the sensitivity filter. This difference in processing time can be partially explained by the difference in the total number of iterations observed during the topology optimization analyses. For this example, the Top2DFVT algorithm, considering the sensitivity filter approach, presents a reduced number of iterations for convergence. See Figure 20. Optimized topologies for the L-bracket beam employing the top99neo algorithm.(URL) 2. Finite-volume theory - In the Eq (4), K is a non-symmetric matrix, then the computational cost of topology optimization based on the FVT is higher than based on the FEM. The authors should comment quantitative values, expressing how slow is the process based on the FVT. Response: The local stiffness matrix in Eq. (4) is non-symmetric, which can lead to higher computational costs compared to FEM-based approaches. To address this, we adopted a modified symmetric stiffness matrix, as shown in Eq. (5), motivated by physical considerations. Specifically, the modified local stiffness matrix allows the adoption of energetically conjugated quantities, i.e., the surface-averaged displacements and the resultant forces acting on the subvolume faces. To clarify this, the following text was added to the manuscript: The modified global stiffness matrix allows the adoption of energetically conjugated quantities, i.e., the surface-averaged displacements and the resultant forces acting on the subvolume faces. This adjustment not only guarantees better physical consistency but also improves computational efficiency by enabling the use of solvers optimized for symmetric systems. As a result, the time required to solve the modified global system of equations is significantly reduced, bringing the computational cost closer to the finite element method-based approaches while retaining the benefits of the finite-volume theory in terms of numerical stability and checkerboard-free solutions. 6. Numerical results - The authors analyzed 3 Case Studies (cantilever deep beam; half MBB beam; L-bracket beam) to show the potentialities of the developed MATLAB code. But they are invited to analyze one of the case studies presented in the paper cited below: A concurrent fibre orientation and topology optimisation framework for 3D-printed fibre-reinforced composites - (Almeida Jr. J, et al., 2023 [Ref 1]) In other words, they should compare the results obtained by the Top2DFVT with the results discussed in the paper. Response: The authors appreciate the reviewer's suggestion to include an additional case study based on the work of Almeida et al. (2023). While their paper presents noteworthy results, particularly in the concurrent optimization of fibre orientation and topology for 3D-printed composites, the authors have opted not to expand the scope of the current manuscript with further case studies. The focus of this article is to present the capabilities of the Top2DFVT code within the context of traditional isotropic materials, and the authors believe the selected case studies effectively demonstrate the tool's potential. However, the authors recognize the value of comparing results with those presented in Almeida et al. (2023) and intend to explore these comparisons in future publications. For now, the authors have chosen to include the following text in the introduction of the manuscript, highlighting recent advancements in topology optimization for anisotropic composites: Recent advances in topology optimization have expanded to include anisotropic composites, optimizing both material distribution and fibre orientation. Almeida et al. (2023) introduced a framework for concurrent optimization of topology and fibre orientation in 3D-printed fibre-reinforced composites, effectively minimizing compliance. This approach, particularly for materials like onyx, enhances stiffness and strength, offering significant benefits for additive manufacturing of high-performance and lightweight structures. Added reference: Almeida JHS Jr, Christoff BG, Tita V, St-Pierre L. A concurrent fibre orientation and topology optimisation framework for 3D-printed fibre-reinforced composites. Composites Science and Technology. 2023;232:109872. doi:10.1016/j.compscitech.2022.109872."
}
]
}
] | 1
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https://f1000research.com/articles/13-805
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https://f1000research.com/articles/13-443/v1
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03 May 24
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{
"type": "Research Article",
"title": "Effect of non-contact induction heating on HA coatings and bone cement, an ex vivo study",
"authors": [
"Robert Kamphof",
"Dr. Giuseppe Cama",
"Jeroen Mesman-Vergeer",
"Dr. Rob G.H.H. Nelissen",
"Dr. Bart G.C.W. Pijls",
"Dr. Giuseppe Cama",
"Jeroen Mesman-Vergeer",
"Dr. Rob G.H.H. Nelissen",
"Dr. Bart G.C.W. Pijls"
],
"abstract": "Background Prosthetic joint infection is a serious complication that can arise after total joint replacement surgery. When bacteria colonise an orthopaedic implant, they form biofilms that protect them from their environment, making them difficult to remove. Treatment is further complicated by a global rise of antimicrobial resistance. These protective mechanisms make treatment of prosthetic joint infection increasingly complex. Non-contact induction heating is an upcoming technology that uses heat to eradicate bacteria that are present on the surface of metallic implants. This study aims to provide insight into the feasibility of using non-contact induction heating on metallic implants that are in direct contact with other biomaterials, such as coatings composed of hydroxyapatite and bone cement composed of poly (methyl methacrylate) (PMMA).\n\nMethods Characterisation of hydroxyapatite coatings and adhesion strength tests were conducted according to standards set by the International Organisation for Standardisation (ISO 13779-2). The fixation strength of acrylic bone cement was tested according to an adapted method from ISO.\n\nResults It was found that non-contact induction heating did not significantly affect the adhesion strength of hydroxyapatite coatings (p=0.697). In contrast to hydroxyapatite coatings, acrylic bone cement softened temporarily as the temperature exceeded the glass transition temperature (83.38 ± 10.88°C). However, the induction heating temperature had no significant effect on the fixation strength after the cement was allowed to cool down (p=0.535).\n\nConclusion This study shows the feasibility of using non-contact induction heating up to 80°C when bone cement or ceramic coatings are present in contact with infected metallic implants.",
"keywords": [
"PJI",
"non-contact induction heating",
"AMR",
"hydroxyapatite",
"calcium phosphate",
"implant coating",
"acrylic bone cement",
"PMMA",
"titanium implants"
],
"content": "Introduction\n\nOne of the adverse outcomes of total joint replacement surgery is prosthetic joint infection (PJI). Commonly caused by gram-positive bacteria, such as S. aureus and S. epidermidis, PJI can have a devastating impact on patients’ lives and comes with a significant financial burden on society.1,2 Due to the formation of protective biofilms by these pathogens, PJI is difficult to treat using conventional antibiotics. Currently, the gold standard to treat PJI is surgical treatment in combination with antibiotics (DAIR: debridement, antibiotics and implant retention). Despite this extensive procedure, DAIR fails in over 30% of all cases, necessitating further surgery for implant removal and replacement.3 Moreover, the increasing incidence of antimicrobial resistance (AMR) further complicates treatment of PJI using antibiotics.4 As it is expected that the problem of AMR will only increase, our reliance on antibiotics to treat infections is not sustainable long-term. Consequently, different treatment modalities are needed, beyond the ones currently available.\n\nNoncontact induction heating (NCIH) is a novel approach to treating bacterial biofilms. NCIH is a treatment method that is under development to combat PJI. NCIH can be used to deliver localised thermal damage to biofilms on metal implants.5 This method could be used as part of DAIR to kill bacteria in places that are hard to clean manually. Potentially, NCIH could even be used to treat implant-related infection non-invasively.6 Previous studies have shown that NCIH, alone or in combination with mechanical cleaning or antibiotics, is capable of significantly reducing or even eradicating bacterial biofilms on titanium surfaces.7–9 Notably, it is possible to perform NCIH on existing implants without the need for modification, meaning that metallic implants that are already inside patients today could be eligible for NCIH treatment.\n\nFor a favourable clinical outcome, it is essential that an orthopaedic implant remains fixed securely. In that respect, it is important to investigate if NCIH treatment does not lead to implant loosening before NCIH can be applied in the clinic. To address this question, this study investigates the effects of NCIH on the adhesion strength of ceramic implant coatings and acrylic bone cement to the metal implant surface, which are the most frequently used biomaterials in direct contact with metallic implants.\n\nCeramic implant coatings made of hydroxyapatite (HA) are commonly used on uncemented prostheses. Because of the similarities of the chemical structure of HA with that of natural bone, HA coatings are highly biocompatible. Implants coated with HA have been shown to expedite and improve implant fixation.10 If NCIH is employed on a coated implant, it is critical to ensure that the integrity of the coating is not compromised by the heat generated in the metallic part of the implant. If this were to happen, coating delamination is expected to cause severe third body wear on prosthetic joints.\n\nPolymeric bone cement is used to fixate prosthetic joints during prosthetic joint replacement surgery. These materials are made by mixing precursor materials to make a pliable putty that hardens into solid poly (methyl methacrylate) (PMMA). Like most polymers, PMMA exhibits a glass transition temperature (Tglass) where the polymer softens considerably. Previous research has shown that bone cement has a glass transition temperature between 80 and 100°C.11 As the prosthetic is held in place by mechanical forces and friction, it is important to investigate the possibility that NCIH treatment loosens the cement’s grip as the temperature approaches Tglass. As this loosening could happen reversibly or irreversibly, it is important to test the grip strength of bone cement both during and after heating.\n\nThus, the aim of this study is to investigate the effect of NCIH on the fixation of metallic implants in direct contact with other HA coatings or PMMA bone cement. The research question is ‘does NCIH of Ti6Al4V weaken the fixation of HA coatings or PMMA bone cement?’. Addressing this question is an important step towards the clinical application of NCIH.\n\n\nMethods\n\nThe effect of exposure to several thermal doses of induction heating on the adhesion of HA coatings and PMMA bone cement was determined. The HA coating represents the scenario of uncemented joint implants. In this scenario, the HA coating acts as a bioactive cue supporting bone to firmly adhere to the coated implant. Therefore, it is critical that NCIH does not lead to delamination of the coating. Coating characterisation and adhesion strength tests were conducted according to standards set by the International Organisation for Standardisation (ISO) in ISO-13779-2.\n\nThe PMMA bone cement represents the scenario of cemented joint implants and the adhesion strength after induction heating and during induction heating was determined. It is important to test both during and after heating, as PMMA bone cement exhibits a Tglass that is close to the effective range of NCIH.11 When heated at or above Tglass, the bone cement may become soft, jeopardizing fixation.12 As there are no standards for testing the fixation of acrylic bone cement, the methods used in this study were adapted from the methods used to test the HA coatings.\n\nThe raw data for these experiments was posted to the Harvard Dataverse at https://doi.org/10.7910/DVN/C1AWLO. Statistical significance testing was performed using student’s t-test for pairwise analysis. In the case of multiple groups, one-way ANOVA (for normally distributed data) or Kruskal-Wallis test (for data that is not normally distributed) was used.\n\nHA coating powder and substrate materials were provided by CAM Bioceramics B.V., a commercial manufacturer of calcium phosphates. Coating of the metal substrates was also performed by CAM Bioceramics B.V. 15 cylinders (25 mm diameter, 30 mm length) made of grade 5 titanium (Ti6Al4V, containing 6% of aluminium and 4% of vanadium) were coated with HA with a thickness of ~50 μm using the plasma spray method. In addition, two Ti6Al4V coupons (38 mm × 25 mm of 1 mm thickness, supplier: https://www.titaniumshop.nl) were also coated. The titanium material from this supplier was previously characterised in more detail and used for an in vitro antimicrobial study.13\n\nPrior to coating, the surface to be coated was sandblasted to provide a rough surface for adequate adhesion of the coating. 4 additional cylinders were sandblasted, but not HA coated to act as controls. After plasma spraying, coating thickness was measured using an eddy current device (Fischer® Fischerscope® MMS®). Reported coating thickness represents the average of 5 measurements on each coating. The properties of the resulting coatings were compared to the requirements for HA coatings for biomedical applications set by ISO 13779-2.14\n\nTwo Ti6Al4V coupons were coated in addition to the cylinders for physiochemical characterisation of the coatings. The surface topography of unmodified Ti6Al4V, sandblasted Ti6Al4V coupons and HA coatings was performed using Scanning Electron Microscopy (SEM) using a Hitachi TM3000. SEM images were taken at various magnifications and at various locations in order to obtain a good impression of the surface topography.\n\nX-ray diffraction (XRD) was used to assess the phase composition and crystallinity ratio of the final coatings. XRD measurements were performed with a Rigaku Miniflex 600. In order to measure the XRD pattern of coated HA, the coating was scraped off the coupon using a scalpel blade. In accordance to ISO 13779-2, the XRD pattern of the scraped coating was measured before and after sintering at 1000°C for 24h to fully crystallise the sample. Sintering was performed using a Nabertherm HT 128 furnace.\n\nXRD patterns were used to obtain the crystallinity ratio and the phase purity according to the method described in ISO 13779-3.15 The phase purity was assessed by qualitatively assessing the presence of peaks not belonging to HA. If such peaks were present, the phase purity was determined by comparing the measured ratio of peak integrals with a calibration curve established by mixing the component phases in a known ratio. The crystallinity ratio was obtained by comparing the peak integrals of 10 peaks known to belong to HA before and after sintering. The XRD measurement for determining the crystallinity ratio was always preceded by measuring the same alumina reference sample. The crystallinity ratio was calculated using the following formula:\n\nWhere S1 is the sum of the integrals of 10 peaks of the uncrystallised sample, S2 is the sum of the integrals of 10 peaks of the fully crystallised sample, R1 is the integral of the main peak of the alumina reference measured before sintering and R2 is the integral of the main peak of the alumina reference measured after sintering.\n\nAll XRD patterns were analysed in PDXL2 (https://www.rigaku.com/support/software/pdxl). PDXL2 is a proprietary software supplied by Rigaku to analyse XRD data generated by Rigaku XRD devices. A free alternative program to analyse XRD data is Profex.16\n\nHeating of the coated cylinders was performed using a commercially available induction heater (HBM portable induction heater 9305) with a frequency of 45 kHz and a maximal power of 1000W featuring a 3.5cm turn coil of solid copper wire with an inner diameter of 28mm. Heating was applied continuously until the intended temperature was reached. The surface temperature of the HA coating was measured using an IR camera (Testo 872) during induction heating. Each coated cylinder was individually placed inside the coil and heated to the target temperature (see Figure 1). The setup was surrounded by wooden panels painted black in order to limit infrared radiation from the surroundings. The final temperature reached by the centre of the coated surface was recorded. The following groups were considered:\n\n• HA Coated control group without heating\n\n• HA Coated group heated to 60°C\n\n• HA Coated group heated to 100°C\n\n• Uncoated control group (to measure the strength of the glue)\n\nThe portable induction heating device is placed around the coated cylinder. The temperature is monitored using an infrared camera. To minimise interference from the environment, the heating is performed in a custom setup made from wooden panels that are painted black.\n\nThe final uncoated group was included to ensure that the glue used in the experiment was stronger than the adhesion strength of the coating, so the coating adhesion strength could be measured properly. The temperature of 60°C was chosen as a possible temperature to use clinically, as this temperature has been shown to be effective against bacterial biofilms.6–8,17 The temperature of 100°C represents a ‘worst case scenario’ that represents the maximum temperature achievable in a wet environment to assess the effect of NCIH on the coating at higher temperatures.\n\nAdhesion strength tests were performed according to ISO 13779-4.18 Cylinders were glued together using FM-1000 epoxy adhesive films. Each HA coated cylinder was glued to an uncoated, sandblasted Ti6Al4V cylinder. For control experiments, two sandblasted cylinders without coating were glued to each other. The adhesion strength was measured using a tensile tester.\n\nAdhesion tests were performed using an EZ50 adhesion tester from Lloyd using a 50kN load cell. The adhesion strength was defined as the force required to completely separate the two cylinders. Results were recorded in kN and converted to MPa using the formula:\n\nWhere σ is the adhesion strength in Pascal, F is the pull force in Newton, and A is the surface area of the cylinders (491 mm2).\n\nAfter the adhesion tests, the interface between the cylinders was inspected and the mode of failure was recorded. The following modes of failure were considered (see Figure 2):\n\n• Adhesive failure of the glue (A)\n\n• Cohesive failure of the glue (B)\n\n• Adhesive failure of the coating (C)\n\n• Cohesive failure of the coating (D)\n\n• Mixed mode of failure\n\nBetween the two cylinders, there is a layer of HA that is plasma-sprayed onto the bottom cylinder, and a layer of fm-1000 glue that is applied by pressing one coated and one coated cylinder together under high temperature. If the cylinders are pulled apart, the setup can fail in 4 different ways depending on which force is the weakest: adhesive forces of the glue (A), cohesive failure of the glue (B), adhesive failure of the coating (C) or cohesive failure of the coating (D). According to ISO-13779-2, only failure modes C and D are acceptable.\n\nFor control experiments, only failure mode A was considered successful. In line with ISO 13379-4, only failure modes C and D were considered successful for coated samples.\n\nTo gain more insight into the possible effect of NCIH on the fixation of metal and bone cement, the pull-out force was measured for metal-cement constructs after the exposed metal has been subjected to various temperature regimes by induction heating. The constructs were made to mimic a cemented total hip or knee replacement implant, where part of the implant is covered by the cement and another part is uncovered.\n\nTo create the metal-cement constructs, the same Ti6Al4V coupons were used that were used for coating with HA. A K-type thermal couple was glued to the metal coupon before inserting the metal into the bone cement at 5 mm depth (see Figure 3). This thermocouple was used to measure the internal temperature of the metal coupon inside the bone cement. Another K-type thermocouple was attached to the metal coupon just outside the metal-cement interface (0 mm into the cement). This thermocouple was used to measure the external temperature of the metal coupon outside the bone cement right at the metal-bone cement interface.\n\nThe green cement is mixed and placed inside a transparent plastic tube, through which a copper tube has been drilled. A Ti6Al4V coupon is then inserted into the soft cement, and the cement is allowed to harden. Two thermocouples are attached to the coupon to measure the internal (inside the cement) and external (outside the cement) temperature of the coupon.\n\nPalacos® R+G (Hereaus™) bone cement was used for all constructs. This bone cement is a high viscosity bone cement containing gentamicin. It is one of the most frequently used bone cements clinically.19 For each package of bone cement 3 constructs were made. The order in which these constructs were prepared was recorded and used for sensitivity analyses, because timing of insertion during the curing phase (early, medium, late) has been shown to affect pull out strength.20 The metal coupons were inserted into the bone cement at a depth of 15 mm, leaving 23 mm uncovered (see Figure 3). Cement was handled and mixed by hand and pressurization was applied in order to mimic the clinical setting as closely as possible. All constructs were cemented by an orthopaedic surgeon (BP). Allocation to the heating groups was done randomly, using a random number generator, to minimize the possible bias by cement order or other factors.\n\nHeating of the coated coupons was performed using a custom built induction heater at 150 kHz featuring a 4-turn solenoid heating coil with an inner diameter of 35 mm in a modified Helmholtz configuration: two connected 2-turn solenoid coils (total 4 turns) with 12 mm spacing between them to allow for uniform heating of the metal coupon. The following groups were considered:\n\n• Control group, no thermal exposure\n\n• Single 70°C heating cycle of the external (not in cement) metal\n\n• Single 100°C heating cycle of the external (not in cement) metal\n\n• Multiple (n=5) 70°C heating cycles of the external (not in cement) metal\n\n• Single 70°C heating cycle of the internal part of the coupon\n\nThe temperature of 70°C was chosen as a possible temperature to use clinically, as this temperature has been shown to be effective against bacterial biofilms.6–8,17 The temperature of 100°C represents a ‘worst case scenario’ to assess the effect of NCIH on the cement at higher temperatures. The reason why 70°C was chosen as the temperature for the tests, as opposed to the 60°C that was chosen for the HA coated samples, is that PMMA is a stronger thermal insulator than HA. In the clinic, this potentially allows for higher temperatures in NCIH treatment without damaging the bone. Furthermore, 70°C is close to the expected Tglass of PMMA bone cement.\n\nAfter heating, a tensile tester (Instron3366) fitted with a 2kN load cell was used to measure the pull-out force of cemented coupons (see Figure 4). The pull-out force (F) was defined as the force required to completely separate the coupon from the cement and was recorded in Newton.\n\nThe custom-built construct is attached to a tensile tester after heating using an induction heater. The tensile tester then pulls apart the construct and measures the force required to do so.\n\nIn order to investigate the strength of PMMA cement under active heating, the samples used for the previous pull-out test were re-used. The Ti6Al4V coupons were re-inserted into the cement using a vise. Subsequently, they were suspended above the ground by a wire and loaded with a weight of 2.5 kg. The coupons were subsequently heated using NCIH until failure. Heating of the coated coupons was performed using a commercially available induction heater (HBM portable induction heater 9305) at 45 kHz with a maximal power of 1000W featuring a 3.5 cm turn coil of solid copper wire with an inner diameter of 28 mm to allow for targeted heating of the cement-metal interface. The internal temperature where the coupon was completely separated from the cement was recorded (see Figure 5).\n\nThe star represents the failure temperature. The temperature goes up and down at regular interval due to manual activation and deactivation of the induction heating device. The star represents the point where the cement failed and heating was ceased.\n\n\nResults\n\nDetailed data on coating thickness, the recorded maximum heating temperature and mode of failure of individual samples can be found in the Underlying data.21 The average coating thickness was 51.9 μm.\n\nThe SEM images show a clear increase in surface roughness between Ti6Al4V before and after sandblasting (see Figure 6). SEM of the HA coating shows the formation of a continuous and fully covering layer of HA has formed on the metal surface. The surface features of the HA coating show where individual molten particles of HA have struck the surface.\n\nCoating samples for phase identification and quantification were collected by scraping the deposited layer of HA from Ti6Al4V coupons (see Figure 7). The XRD pattern show a slight bump at 2θ ~30.25, which indicates the formation of a small amount (6% w/w) of beta tricalcium phosphate (β-TCP). No evidence was found in XRD for the formation of other calcium phosphate phases or of calcium oxide. The crystallinity ratio was calculated to be 70%, calculated from the relative integral of 10 peaks before and after sintering at 1000°C. Table 1 summarises the results of the physiochemical characterisation of the HA coatings. These results are compared to the requirements set by ISO 13779-2 for HA coatings.\n\nCrystallisation was performed by heating the powder scraped from a coated sample to 1000°C for 24 hours.\n\nThe adhesion strengths of Ti6Al4V cylinders are shown in Figure 8. Most failure modes were of type A for uncoated control samples and C for coated samples. However, two controls exhibited a mixed A/B mode of failure with some cohesive failure of the glue, most likely due to incorrect levelling of the surface of the cylinders. One sample from the 100°C group was rejected despite a mode C failure after a human error made it unsuitable for testing. After omission of this sample from further analysis, a sensitivity analysis was performed, showing that all results of this study remained similar and the conclusions did not change. On average, the strength of coated samples and uncoated controls was 80 MPa and 85 MPa, respectively (T-test p = 0.019). This indicates that the FM-1000 glue used for the experiment was stronger than the adhesion strength of the HA coating, making it suitable for the experiment. It is important that the glue is stronger than the coating in order to properly distinguish between different modes of failure. No significant difference in adhesion strength was measured among coated samples grouped by heating temperature (one-way ANOVA p = 0.697).\n\nThe results of the post-heating pull-out experiments are shown in Figures 9 and 10. Detailed data on the pull-out force of individual samples can be found in the Underlying data.21 Because there is no proper standard for measuring the pull-out strength of PMMA bone cement, the procedure for measuring the adhesion strength for HA coatings was followed as closely as possible.\n\nIndividual measurements are colour coded by the order in which they were cemented: first construct in a batch (blue), second construct in a batch (red) and third construct in a batch (green).\n\nNo clear relationship between the heating temperature and the pull-out force was observed (Kruskal-Wallis test: p = 0.535). Likewise, there was no significant difference between controls and grouped heated samples (T-test: p = 0.513). Conversely, when the data was grouped by the order in which they were cemented, the second coupon from a batch of cement appeared to have an increased strength compared to the first and third coupons (Kruskal-Wallis test: p = 0.0757). Even after correction for the cement order, no association between the thermal dose and pull-out force was found.\n\nThe internal temperature that caused failure for re-inserted samples loaded with a weight of 2.5 kg was 83°C with a SD of 11°C. One sample was excluded because the titanium coupon did not disengage from the cement at 150°C. Detailed data on the pull-out force of individual samples can be found in the Underlying data.21\n\n\nDiscussion\n\nThe results of this study show that the adhesion strength of HA coatings is unaffected by heating to 60°C or 100°C. Similarly, no relationship was established between the pull-out force and the heating temperature of cemented coupons. However, there was an association of the cementation order and the pull-out strength. Furthermore, it is clear that heating bone cement above its glass transition temperature results in a reversible softening that could potentially allow an implant to loosen if force is applied during active heating.\n\nThe physiochemical requirements for HA coatings in medical devices is outlined by ISO 13779-2.14 The minimum adhesion strength for any given coating is 10 MPa, with an average no lower than 15 MPa. Furthermore, ISO 13779-2 stipulates that the crystallinity ratio of an HA coating must be above 45% by weight and can contain no more than 30% of other calcium phosphate phases and no more than 5% calcium oxide. Based on these requirements, the coatings made in this study adhere to the ISO standard.\n\nThe XRD pattern of the coated sample indicates some loss of crystallinity and the formation of a small amount of β-TCP. β-TCP, with chemical formula Ca3(PO4)2, is a different calcium phosphate phase known to be more bioactive than HA due to its higher solubility. HA can convert into β-TCP when subjected to temperatures above 1000°C.22 The formation of β-TCP in the HA coating (6%) can be explained by the high temperatures experienced by the coating powder during the plasma spray process, but remains below the upper limit (30%) specified by ISO 13779-2. Moreover, the calculated crystallinity ratio (70%) is within the requirements (45%) set by ISO 13779-2. Surface roughness measurements and trace element analysis are also mentioned in ISO 13779-2; however, these measurements were not performed in this study as they fall outside the scope of this investigation. It is not expected that these parameters influence the change in adhesion strength after NCIH treatment.\n\nThe difference between uncoated control samples and coated samples was 4.17 MPa, which is slightly smaller than the requirement of 5 MPa set by ISO. The ISO requirement is set to be able to properly distinguish between failure of the glue and failure of the coating. Nevertheless, a statistically significant difference was found between controls and coated samples. The coating adhesion strength for the HA coatings tested in this study (average of 80 MPa across all groups) is well above the requirement of 10MPa set by ISO 13779-2. That means these coatings would be acceptable for orthopaedic purposes. The fact that no significant change in adhesion strength was found after NCIH is unsurprising, as the coating particles are already exposed to extremely high temperatures during the plasma spraying process. This study shows that there is no increased likelihood of implant failure due to coating delamination when using NCIH on coated implants.\n\nThe glass transition temperature (Tglass) is a property of amorphous solid materials. Below Tglass, the solid is in a ‘glassy’ state, i.e., rigid and inflexible. Above Tglass, the material becomes flexible and rubbery. Tglass can be either below room temperature (e.g., rubber) or above room temperature (e.g., polystyrene). For fresh, dry bone cement, Tglass is in a range of 80-100°C, meaning bone cement is in its ‘glassy’ state under physiological conditions, which gives it excellent properties for bone fixation.11 When the temperature exceeds Tglass, bone cement is known to weaken considerably, which could compromise implant fixation during NCIH treatment. Interestingly, this phenomenon was used to facilitate removal of bone cement in previous research.23 As the temperatures intended for NCIH treatment (60-80°C) are close to the Tglass of bone cement, it is important to establish the impact of NCIH on implant fixation. In order to mimic the clinical situation as closely as possible, the cemented samples were prepared by an orthopaedic surgeon (BP).\n\nThe external temperature was recorded to reach up to 400°C in the group where the internal temperature was made to reach 70°C. Nevertheless, no noticeable weakening of bone cement was found even after heating to these extreme temperatures. Clearly, these extreme conditions exceed those that will be used in the clinic. Nevertheless, no permanent weakening of the cement was observed when the cement was allowed to cool down before attempting to remove the coupons, indicating that the mechanical properties of bone cement are not irreversibly compromised upon heating with NCIH. It should be noted that the surface characteristics of the medial-grade Ti6Al4V used in this study have been described in detail in previous research.13 Generally, the surface finish of the coupons is much smoother than that of most commercial implants.24 As such, it is expected that the grip strength reported here underestimates the clinical situation.\n\nDespite the lack of evidence of weakening of the cement after heating, there was considerable spread in the measured pull-out force, with pull-out forces varying from 330 to 1970N. This spread could partially be explained by the timing of the fixation of the Ti6Al4V coupons relative to the mixing of the precursors. From each batch of bone cement, three samples were cemented in place. Samples that were cemented immediately after mixing were found to be weakest, while the second sample was the strongest. There was an increasing trend in the variability in the pull-out strength going from the first to the third sample. This increased variability is likely due to variations in the speed at which the samples were prepared. The importance of the timing of implant cementation is in line with previous research and the experience of Orthopaedic surgeons.20 Other sources of variability most likely include variations in the angle of the sample and cementation technique. However, these variations are expected to average out due to the random allocation of the sample between the groups.\n\nWhen force was applied to the cemented coupons during active heating, it became clear that the cement became slightly pliable upon heating to >80°C, allowing the coupon was able to slip out. This point likely corresponds to the glass transition temperature of the bone cement, which was reported to fall around 90°C for dry cement samples of this brand.11 The loosening temperatures observed in this study are above the intended temperatures of NCIH (70°C or less); therefore, it is not expected that NCIH treatment will lead to implant loosening. Nevertheless, as Tglass differs between cement brands and the age of the cement, it would be prudent to stabilise the patient’s limb during NCIH until the treatment is finished, if that patient uses a cemented prosthesis.11 As this study shows that the weakening of bone cement is non-permanent, there should be no permanent effect on the prosthesis fixation after the treatment is over even if Tglass is exceeded for a short period of time.\n\nThere are some limitations to this study that should be considered. Most importantly, it should be noted that all testing samples were exposed to air during the heating experiments and strength tests, as opposed to a biological environment. One consideration is that the properties of PMMA cement and HA coatings could change over time in vivo due to degradation by physical and biological processes. Specifically, Tglass for PMMA cement tends to decrease with time under biological conditions.11 Thus, it is possible that Tglass is exceeded by NCIH heating in patients with older prostheses. A second limitation of our study is that the rate of heating and heat dissipation are different for samples in an ambient environment, compared to in vivo conditions. It is expected that implanted metal will heat more slowly, as surrounding tissue acts as a heat sink. While this means the temperature can be better controlled in vivo, it also means that the thermal dose required to reach the desired temperature will be higher. To mitigate this potential risks the temperatures used in study are a ‘worst case scenario’ that exceeds those desired in NCIH treatment.\n\nDespite these limitations, this study is able to assess the impact of NCIH on the fixation of HA implant coatings and PMMA bone cement with a high degree of fidelity. Samples were prepared using industrial equipment and medical-grade materials. Furthermore, the coating adhesion tests were conducted using industry-standard tests published by ISO. Pull-out experiments on cemented coupons were adapted from those same tests to maximise reliability of the data. Based on our results, NCIH does not affect the fixation of uncemented (HA-coated) and cemented implants.\n\n\nConclusion\n\nIt was shown that induced temperatures up to 100°C do not decrease the adhesion strength of HA coatings, as tested using certified methods set by ISO 13779-2. In contrast to the HA coatings, bone cement was found to weaken above 80°C, allowing the implant material to be pulled out. This weakening effect is most likely associated with the glass transition temperature of the material. This weakening was shown to be reversible, as there was no significant difference between the fixation strength of any of the groups after cooling. A considerable variability in the fixation strength was found among different samples, which could partially be explained by differences in the timing of the cementation.\n\nThis publication is part of the project DARTBAC (with project number NWA.1292.19.354) of the research programme NWA-ORC which is (partly) financed by the Dutch Research Council (NWO).\n\nThis article was written in collaboration with CAM Bioceramics B.V., situated in Leiden, The Netherlands. CAM Bioceramics B.V. is a contract development and manufacturing organisation of Orthobiologic Calcium Phosphates.\n\nThe authors would like to acknowledge the work of Larbi Douz, Rob Bockhorst and Marco Azier from CAM Bioceramics B.V. for their contribution in the preparation of the HA coatings and measurement of the coating adhesion strength.\n\n\nEthics and consent\n\nEthical approval and Consent not required.",
"appendix": "Data availability\n\nHarvard Dataverse. Supplementary data - Effect of non-contact induction heating on HA coatings and bone cement: an ex vivo study. DOI: https://doi.org/10.7910/DVN/C1AWLO. 21\n\nThis project contains the following underlying data:\n\n• Supplementary data.docx. (document containing information such as adhesion strength, pull-out force, coating thickness, and final temperature reached for each sample).\n\nData is available under the terms of the Create Commons “Attribution 4.0 International” data waiver (CC-BY 4.0 Attribution-Only).\n\n\nReferences\n\nTriffault-Fillit C, Ferry T, Laurent F, et al.: Microbiologic epidemiology depending on time to occurrence of prosthetic joint infection: a prospective cohort study. Clin. Microbiol. Infect. 2019; 25(3): 353–358. PubMed Abstract | Publisher Full Text\n\nKlouche S, Sariali E, Mamoudy P: Total hip arthroplasty revision due to infection: A cost analysis approach. Orthop. Traumatol. Surg. Res. 2010; 96(2): 124–132. PubMed Abstract | Publisher Full Text\n\nZhu MF, Kim K, Cavadino A, et al.: Success Rates of Debridement, Antibiotics, and Implant Retention in 230 Infected Total Knee Arthroplasties: Implications for Classification of Periprosthetic Joint Infection. J. Arthroplast. 2021; 36(1): 305–310.e1. PubMed Abstract | Publisher Full Text\n\nMurray CJ, Ikuta KS, Sharara F, et al.: Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399: 629–655. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPijls BG, Sanders IMJG, Kuijper EJ, et al.: Segmental induction heating of orthopaedic metal implants. Bone Jt. Res. 2018; 7(11): 609–619. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChopra R, Shaikh S, Chatzinoff Y, et al.: Employing high-frequency alternating magnetic fields for the non-invasive treatment of prosthetic joint infections. Sci. Rep. 2017; 7(1): 7514–7520. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPijls BG, Sanders IMJG, Kujiper EJ, et al.: Induction heating for eradicating Staphylococcus epidermidis from biofilm. Bone Jt. Res. 2020; 9(4): 192–199. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPijls BG, Sanders IMJG, Kuijper EJ, et al.: Effectiveness of mechanical cleaning, antibiotics, and induction heating on eradication of Staphylococcus aureus in mature biofilms. Bone Jt. Res. 2022; 11(9): 629–638. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPijls BG, Sanders IMJG, Kuijper EJ, et al.: Synergy between induction heating, antibiotics, and N-acetylcysteine eradicates Staphylococcus aureus from biofilm. Int. J. Hyperth. 2020; 37(1): 130–136. PubMed Abstract | Publisher Full Text\n\nHorváth T, Hanák L, Hegyi P, et al.: Hydroxyapatite-coated implants provide better fixation in total knee arthroplasty. A meta-analysis of randomized controlled trials. PLoS One. 2020; 15(5): e0232378–e0232313. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKuehn KD, Ege W, Gopp U: Acrylic bone cements: Mechanical and physical properties. Orthop. Clin. North Am. 2005; 36(1): 29–39. Publisher Full Text\n\nBrooks AT, Nelson CL, Stewart CL, et al.: Effect of an ultrasonic device on temperatures generated in bone and on bone-cement structure. J. Arthroplast. 1993; 8(4): 413–418. PubMed Abstract | Publisher Full Text\n\nvan Dun SCJ , Verheul M, Pijls BGCW, et al.: Influence of surface characteristics of implant materials on MRSA biofilm formation and effects of antimicrobial treatment. Front. Microbiol. 2023; 14(April): 1–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nISO 13779-2 - Implants for Surgery - Hydroxyapatite - Part 2: Thermally Sprayed Coatings of Hydroxyapatite.2018.\n\nISO 13779-3 - Implants for Surgery - Hydroxyapatite - Part 3: Chemical Analysis and Characterization of Crystallinity Ratio and Phase Purity.2018.\n\nDoebelin N, Kleeberg R: Profex: A graphical user interface for the Rietveld refinement program BGMN. J. Appl. Crystallogr. 2015; 48: 1573–1580. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPijls BG, Sanders IMJG, Kuijper EJ, et al.: Non-contact electromagnetic induction heating for eradicating bacteria and yeasts on biomaterials and possible relevance to orthopaedic implant infections: in vitro findings. Bone Jt Res. 2017; 6(5): 323–330. PubMed Abstract | Publisher Full Text | Free Full Text\n\nISO 13779-4 - Implants for Surgery - Hydroxyapatite - Part 4: Determination of Coating Adhesion Strength.2018.\n\nLROI: Online LROI Annual Report 2023.2022. Reference Source\n\nHunt S, Stone C, Seal S: Timing of femoral prosthesis insertion during cemented arthroplasty: Cement curing and static mechanical strength in an in vivo model. Can. J. Surg. 2011; 54(1): 33–38. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKamphof R: Supplementary data - Effect of non-contact induction heating on HA coatings and bone cement: an ex vivo study.Publisher Full Text\n\nChoi D, Kumta PN: An alternative chemical route for the synthesis and thermal stability of chemically enriched hydroxyapatite. J. Am. Ceram. Soc. 2006; 89(2): 444–449. Publisher Full Text\n\nGhanem M, Koenig A, Dehn F, et al.: Thermomechanical method for cement extraction in revision arthroplasty. Eur. J. Orthop. Surg. Traumatol. 2017; 27(8): 1125–1130. PubMed Abstract | Publisher Full Text\n\nNicolas-Silvente AI, Velasco-Ortega E, Ortiz-Garcia I, et al.: Influence of the titanium implant surface treatment on the surface roughness and chemical composition. Materials (Basel). 2020; 13(2): 1–13. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "298322",
"date": "27 Aug 2024",
"name": "Govinda Kapusetti",
"expertise": [
"Reviewer Expertise Orthopedic materials",
"smart devices",
"and martials",
"theranostics"
],
"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 was interesting but need to clarify the following issues before indexing;\nThe study found that NCIH up to 100°C did not significantly impact the adhesion strength of HA coatings. This suggests that the use of NCIH on HA-coated implants is feasible without risking coating delamination, which is crucial for maintaining the integrity of the implant. The study also investigated the impact of NCIH on acrylic bone cement. The bone cement softened as the temperature approached and exceeded the glass transition temperature (around 83°C). However, this softening was reversible, and no significant loss of fixation strength was detected once the cement cooled down. Verify the statement that PMMA is more thermally stable than HA, and correct it. The study focuses on the effects of NCIH at temperatures up to 100°C. Consider conducting additional experiments at slightly higher temperatures (e.g., 110°C or 120°C) to determine the upper limit at which HA coatings and bone cement maintain their structural integrity. This will provide a more comprehensive understanding of the safe operating range for NCIH. The study appears to focus on short-term heating effects. It would be beneficial to perform experiments that expose samples to prolonged heating durations to simulate potential clinical scenarios where longer exposure might be necessary. This will help determine if there are cumulative effects that could compromise material properties over time. Perform chemical stability tests to determine if NCIH causes any degradation or chemical alterations in HA coatings or bone cement. For instance, Fourier-transform infrared spectroscopy (FTIR) or Raman spectroscopy could be used to detect any changes in the chemical bonds or phase transitions. Given that NCIH is being considered for clinical applications, conducting in vitro biocompatibility studies on materials post-NCIH treatment would be crucial. This could involve cell viability assays, such as MTT or Live/Dead assays, using osteoblasts or fibroblasts to assess if the heated materials induce any cytotoxic effects. Thermal imaging or infrared thermography is employed to visualize and quantify the heat distribution across the HA coatings and bone cement during NCIH. This will help ensure that the heating is uniform and does not create localized hotspots that could potentially damage the material or surrounding tissues. The study has strong potential for clinical impact. By exploring the feasibility of using NCIH in a medical context, the research opens up new possibilities for non-invasive treatment of implant-related complications, which could significantly benefit patient outcomes. In conclusion, this paper presents a well-executed and innovative study that significantly contributes to the understanding of non-contact induction heating (NCIH) and its effects on HA coatings and bone cement. The research is grounded in a strong rationale, and the findings have important implications for both materials science and clinical applications. While there are areas for further exploration, particularly regarding long-term effects and practical implementation, the study provides a solid foundation for future research. It has the potential to influence advancements in the treatment of implant-related complications.\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?\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": "12314",
"date": "28 Aug 2024",
"name": "Robert Kamphof",
"role": "Author Response",
"response": "Dear reviewer, I would like to thank you for reading our article and for providing your suggestions for improvement. Let us respond to your feedback on a point-by-point basis. 1. This is correct. Our study has indeed found that HA coatings maintain their mechanical stability when heated up to 100°C using NCIH. 2.This is also correct. The glass transition temperature is a transition point where a polymer transforms from a solid and brittle ‘glassy’ state to a soft and malleable ‘rubbery’ state. The value of the glass transition temperature is dependent both on the chemical composition of the polymer as well as its chain length. 3. My apologies, but we cannot find the section in the manuscript where we write that PMMA is more thermally stable than HA. Could you point us towards the relevant section, so we can revise it? We would like to amend that section to avoid confusion. 4. We do not believe that there is an added value in performing experiments at higher temperatures for this study, as the maximum temperature of NCIH is constrained because to 100°C of its intended use in a biological (i.e., aqueous) environment. Having said that, we think more fundamental research on the thermal properties of HA and PMMA, such as TG/DSC analysis, would be interesting and insightful. 5-7. Thank you for your suggestions for further research. While we consider these suggestions very interesting, and we would like to see these questions answered in the future, we consider them to be outside the scope of our current study. We intended to answer the research question: ‘does NCIH of Ti6Al4V weaken the fixation of HA coatings or PMMA bone cement?’. We hope you agree with our assessment. 8. Thank you for your praise. We used a thermal camera to follow the temperature changes of the HA coated Ti6Al4V cylinder and we can confirm that no hotspots formed during heating, and that heating was uniform across the circular surface of the cylinder. The heating of Ti6Al4V coupons using NCIH was previously described in the paper: ‘Induction heating for eradicating Staphylococcus epidermidis from biofilm’ (https://doi.org/10.1302/2046-3758.94.BJR-2019-0274.R1). We intend to publish more research on NCIH, including more thermal images, in the near future. 9-10. Thank you for your kind feedback. We hope that our research can help in developing NCIH technology further so it can be safely and effectively employed in a clinical setting. Thank you again for your kind feedback. I hope you consider all your questions and concerns fully addressed by this response. If you have any further questions, please let us know."
}
]
},
{
"id": "319607",
"date": "11 Sep 2024",
"name": "Joeri Kok",
"expertise": [
"Reviewer Expertise Orthopaedic biomechanics",
"Numerical analysis",
"Medical image 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 work that the authors present provides novel insight on the adhesion of (bio)materials hydroxyapatite and PMMA to Ti6Al4V during induction heating. Overall the manuscript is well-written. The introduction and aim of the work is clear and the methodology largely follows ISO standards making it reliable and repeatable. I do have some remaining questions regarding the strength of the study.\n1. The number of samples per group severely hinders drawing any hard conclusions. First of all, the number of samples per group is not mentioned in the methods and is only clear from the supplementary material. Secondly, I believe that it is inappropriate to use parametric tests that assume normality for the statistics. With low sample numbers non-parametric tests should be used because tests for normality cannot be relied upon. In the case of the tests with bone cement I would even like to suggest to remove the statistics completely and stick to only describing the observations. With groups of 2-4 samples standard deviations don't mean much and statistical significance cannot be reached, thus potentially giving readers a false impression of similarity between groups.\n\n2. For the adhesion experiments with HA, the supplementary material shows that the failure mode is always 'mode C'. I understand the difference between the modes but how are the failure modes determined? Can you visually see the difference between failure mode C and D, or a mix? It would be valuable to include photos in a figure of each observed failure mode.\n3. For the in-situ induction heating tests. How are the coupons exactly reinserted using a vise? Why are they reinserted in the same cement and not put into new cement? Does the reinsertion not make the connection dependent on the previous heating methods?\n4. Based on figure 5: Overall this part of the study is not very well explained. What is on the horizontal axis? If this is the time, why not start at t=0? Why was manual activation and deactivation of the heating device required? Why such short intervals? Does the speed of heating influence the failure temperature?\n5. On average a difference between adhesion of the glue and the HA coating is shown. I already somewhat doubt the significance of this measure, additionally, figure 8 shows overlap between control and the other groups. Regardless of the statistical difference this suggests that there will be samples where the adhesion/cohesion of the glue will fail before that of the HA coating. Coming back to comment 2, I'm very curious about how the failure was observed and defined for each individual sample.\n6. The results about the batches are interesting, but they come somewhat out of the blue. I suggest explaining this also in the methods with an estimate of the variation in time between mixing and inserting the coupons.\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?\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? Partly",
"responses": [
{
"c_id": "12556",
"date": "22 Oct 2024",
"name": "Robert Kamphof",
"role": "Author Response",
"response": "Dear reviewer, Firstly, we would like to thank you for providing feedback so we can improve our article. We have made some changes to our article based on your feedback, and we would like to address some of your comments here. We agree that the number of replicates per experimental condition was unclear in the first version our article, and we have adapted the methods section accordingly. We have also made some changes to clarify our workflow. Regarding the statistics, we fully agree with your assessment. Using parametric tests was not suitable for our data set. In general, there is a growing resistance against the (wrongful) use of p-values (e.g. “Scientists rise up against statistical significance”, https://doi.org/10.1038/d41586-019-00857-9). Therefore, we have chosen to remove statistical tests from our manuscript, focusing instead the observed values. Moreover, we have changed the error bars in our images to represent the 95% CI instead of the standard deviation, and we have clarified this in the methods and the figure captions. Indeed for the HA coated experimental groups, the mode of failure was always C, indicating that the adhesive strength of the coating was lower than the cohesive strength. The failure mode is determined by visual inspection of the fracture plane after failure. Failure mode D, indicating cohesive failure of the coating, would be visible by the presence of HA on both sides of the fracture plane. This was not the case in our experiments; instead, the coating was always stripped completely from the substrate by the glue. We have added images of the different failure modes in the supplementary data. Thank you for this excellent question. The coupons were re-inserted into their respective cement constructs by pressing them into the slot in the cement as far as possible by hand, then opening a manual vise and closing it onto the construct until the coupon occupied its original position. The reason why we opted to re-use the constructs was due to the large variation in adhesion strength of these constructs. If we used fresh ones, their adhesion strength would be unknown, and it would be difficult to estimate the effect of heating in situ. As a control experiment, we have repeated our first experiment on re-inserted coupons, and found that the resulting adhesion strength remained relatively constant even when the coupon was re-inserted three or four times. This shows us that the observed adhesion strength under room temperature conditions is mostly due to friction, and that the cement is not permanently damaged by failure. We used pulsed heating to achieve to ensure homogenous heating of the coupons. Inhomogeneities in the magnetic field or the Ti6Al4V-PMMA constructs could lead to uneven heating and the formation of hot spots if constant heating was applied. By applying a heating duty cycle, any hot spots had time to diffuse. Secondly, duty cycling reduced the change of overheating in the induction coil itself. We have made some changes to the manuscript to clarify these points, and we have removed Figure 5 since we agree it raises more questions than it answers. It is true that the difference between the measured strength of the coatings differed only slightly from the strength of the glue. Ideally, a larger difference would be observed to properly distinguish between the failure modes (NB: ISO-13779-2 demands an average difference of 5MPa between the glue and the samples, which we achieved, if only narrowly). However, the strength of the control does not change the main findings of our study, namely that that no difference was observed between the coated groups heated at different temperatures. Thank you for your feedback on this. We have made some changes to the manuscript. We estimate that the time between the cementation between each sample was about 2.5 minutes. Naturally, there was some variation in this time, which explains the increasing spread in the samples with increasing cement order. We would like to thank you again for your feedback. We hope to have answered your questions and remarks in a sufficient manner and that you are happy with the changes made to the document."
}
]
}
] | 1
|
https://f1000research.com/articles/13-443
|
https://f1000research.com/articles/11-129/v1
|
01 Feb 22
|
{
"type": "Case Report",
"title": "Case Report: Placental site trophoblastic tumor revealed by a clinical pelvic abscess",
"authors": [
"Souayeh Nesrine",
"Hajer Bettaieb",
"Wael Mbarki",
"Ben Brahim Ehsen",
"Helal Imen",
"Ben Nasr Mehdi",
"Oueslati Hedhili",
"Hsayaoui Najeh",
"Chaouki Mbarki",
"Souayeh Nesrine",
"Hajer Bettaieb",
"Wael Mbarki",
"Ben Brahim Ehsen",
"Helal Imen",
"Ben Nasr Mehdi",
"Oueslati Hedhili",
"Hsayaoui Najeh"
],
"abstract": "We report an uncommon clinical presentation of a placental site trophoblastic tumor. The patient presented initially with abdominal pain with, fever, bleeding and pelvic mass on ultrasonography leading to the wrong diagnosis of a pelvic abscess. Dilation and curettage were performed and pathological examination confirmed the diagnosis. of placental site trophoblastic tumor. Therefore, she underwent abdominal hysterectomy. Four years after surgery, the patient is still disease free. Gestational trophoblastic diseases should be considered in every patient presenting abnormal uterine bleeding after delivery or pregnancy loss despite the associated symptoms being very unusual.",
"keywords": [
"Gestational Trophoblastic Disease",
"Placenta Diseases",
"Trophoblastic Tumor",
"Placental Site",
"pathology."
],
"content": "Introduction\n\nPlacental site trophoblastic tumor (PSTT) is a rare tumor, representing 1% of gestational trophoblastic diseases.1,2 It mainly affects women of childbearing age after delivery or pregnancy loss.1–3 In this paper, we report a case of placental site trophoblastic tumor diagnosed by an array of pelvic abscess associated with bleeding occurring two months after delivery. The evolution, after surgical treatment by hysterectomy, was favorable.\n\n\nCase report\n\nWe report the case of an unemployed 32-year-old Arabic woman, gravida 1 and para 1, without medical history, gave birth naturally and without complications to a full-term healthy newborn. Two months after her delivery, she consulted our department with persisting metrorrhagia associated with fever of 39°C. The patient’s examination revealed that the bleeding has been noted since the delivery day and it had increased two days earlier.\n\nA physical examination revealed a fever of 39.5°C and abdominal tenderness. The blood pressure was 110/70 mm Hg and the heart rate was 82 beats/mn. Furthermore, there was no specific digestive or urinary symptom. Per speculum examination, the cervix was enlarged with purulent vaginal discharge. On digital pelvic examination, the uterus was increased in size accessed at 12 week gestation and its mobilization was painful. Blood tests showed an inflammatory syndrome with a C-reactive protein at 200 mg/l [≤ 6mg/l] and white blood cells at 17000/mm3 [4000-10000/mm3]. The beta-human chorionic gonadotropin (β-HCG) rate was positive at 674 U/l [< 5U/l]. The transvaginal sonography showed a large sized uterus containing an echogenic heterogeneous endometrial mass, vascularized on Doppler examination. This process seemed to invade the myometrium in part. In addition, ultrasound showed an average effusion in the Douglas' pouch (Figure 1) with a probable left adnexal abscess.\n\n(A) Echogenic tumor occupying the uterine cavity (arrow) with infiltration of the myometrium; (B) appearance vascularized tumor at color Doppler.\n\nLaparoscopic adnexal drainage and endometrial curettage were performed. The infectious episode resolved promptly with antibiotics; gentamicin 160 mg per day for 5 days metronidazole 500 mg three times a day for 15 days and cefotaxim 1g three times a day for 15 days. Pathological examination of the endometrial curettage specimen reported a proliferation of large tumor cell with eosinophilic cytoplasm and nuclear atypia, infiltrating the myometrium. These cells were positive for pro inflammatory cytokine (IL6) in the immunohistochemistry studies and the final diagnosis was a placental site trophoblastic tumor.\n\nA laparotomic hysterectomy with preservation of ovaries was performed. On gross examination there was a mass of 6 cm localized to the myometrium of bluish appearance with areas of hemorrhage and necrosis. The tumors had ill-defined borders and invaded into the myometrium (Figure 2). Pathological examination was similar to that described in the curettage specimen, showing a proliferation of monomorphic intermediate trophoblasts (Figure 3A). The tumor cells demonstrated nuclear atypia, eosinophilic cytoplasm (Figure 3D) and myometrial invasion (Figure 3B,C). Extensive necrosis, hemorrhage and vascular invasion are observed (Figure 3E). The final pathology report confirmed the diagnosis of PSTT infiltrating the myometrium. The postoperative course was favorable. The patient had a regular follow-up every month for the first year combining a clinical examination and a serum level of β-HCG. She had a clinical check-up and pelvic ultrasound every year for two years, no sign of recurrence was noted. Four years after surgery, the patient is still disease free.\n\n(A) Peri operative view showing increased uterine size, yellowish area seat (arrow); (B) appearance of the tumor to cut, yellowish tumor occupying the uterine cavity and infiltrating the myometrium.\n\n(A) Monomorphic cell proliferation of intermediate trophoblast; (B, C) tumor cells infiltrate the myometrium form of clusters, dissociating smooth muscle bundles (B: low magnification, C: magnification); (D) proliferation of large cells with eosinophilic cytoplasm and lobulated nucleus; (E) home of tumor cells with the presence of vascular emboli.\n\n\nDiscussion\n\nIn 1895, Marchand first described PSTT and named it atypical chorioepithelioma.4 In 1981, Scully and Young described the morphological details and recognized it as a neoplastic process, and named it PSTT.5 PSTTs are a rare subtype of gestational trophoblastic disease, accounting for less than 1% of all cases.1,2,6 It mainly affects women of childbearing age and it is seen in patients between 19-62 years, with an average age of 30 years.1–3,6,7 PSTT can occur after a normal pregnancy, abortion, term delivery, ectopic pregnancy or molar pregnancy.1–3,6–8 Here we reported a case of PSTT occurring after a normal pregnancy. This pathology may occur months to years after pregnancy with the average interval between the antecedent pregnancy and diagnosis being 16 to 18 months.1–3,6,9 Diagnosis of PSTT can be difficult due to the nonspecific clinical signs. Abnormal uterine bleeding is the most common presenting feature.1–3,6–9 Metrorrhagia can also be associated with amenorrhea.1,8 The peculiarity of our case lies in the fact that the tumor was manifested by an array of pelvic abscess associated with bleeding; such clinical presentation was rare in literature.8 On digital pelvic examination, the uterus can be enlarged or normal sized.2,8 A wide range of other rare symptoms have also been reported, including galactorrhea, virilization, nephrotic syndrome, and polycythemia.2,8 PSTT can also be revealed by metastasis.2,7 The serum levels of β-hCG are usually in the range of 1000-2000 mIU/mL.1–3,6,9 The origin of PSTT is the intermediate trophoblast cells which secrete little beta HCG and a lot of placental lactogenic hormone.6,9\n\nOn gross examination, the tumors are located primarily in the endomyometrium, presenting as polypoid or nodular masses, with a variable diameter up to 10 cm.1,6 The sectioned surfaces of the tumors are solid, often fleshy, and usually yellow with necrosis, and hemorrhage.1,2,6 The tumor may extend into the cervix or infiltrate the serous, the adnexa or the round ligaments.2 In our case, the tumor invaded the myometrium without reaching the serous. The diagnosis of PSTT is based on pathological examination.\n\nOn microscopic examination, we typically find a proliferation of intermediate trophoblastic cells without chorionic villi, which infiltrate muscle fibers.2 Vascular invasion, necrosis and hemorrhage are also often observed.2\n\nThe tumor is composed of a relatively monotonous population of polygonal cells with nuclear atypia and moderately abundant cytoplasm that can be amphophilic, eosinophilic or clear.1,2 The distinctive pattern of vascular invasion and deposition of fibrinoid material are the key diagnostic features.1–3 Usually, PSTTs are benign tumors. However, they have an unpredictable malignant potential and between 10 and 20% of patients have metastatic disease at the time of presentation.1,2,7,10 Metastasis site include peritoneum, vagina, lung, liver and brain.\n\nHysterectomy without bilateral oophorectomy is the gold standard in PSTT management.2,10 In fact, this entity is particularly less responding to chemotherapy than hydatiforme mole, invasive mole and choriocarcinoma.2,10 When there is extension beyond the uterus, surgical treatment should be associated to chemotherapy.2,10\n\nActually, the FIGO anatomical staging system is the strongest predictor of patient outcome presenting with PSTT.2,7,10,11 After surgical treatment, patients should be followed up during years to optimize the chance of detecting a relapse or metastasis.7,10,11\n\n\nStrengths and limitations\n\nThis case report is interesting since it’s the first reporting PSTT simulating a pelvic abscess. However, PTTT are rare which prevents researchers from realizing large scale studies in order to develop valid management protocols.\n\n\nConclusion\n\nAlthough PSTTs are extremely rare worldwide, the diagnosis should be considered during the post-partum and post-abortion periods if there is persistent metrorrhagia. After surgical treatment, the follow up is needed to be accurate, to help recognize a relapse or metastasis.\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 clinical details and clinical images was obtained from the patient.",
"appendix": "References\n\nBouchet-Mishellany F, Ledoux-Pilon A, Darcha C, et al.: Tumeurs trophoblastiques gestationnelles: a propos d’un cas de tumeur trophoblastique du site placentaire et d’un cas de tumeur trophoblastique epithelioide. Ann. Pathol. 2004; 24: 167–171. Publisher Full Text\n\nDevouassoux-Shisheboran M, Allias F, Mathevet P, et al.: Gynecopathology: Pathologie gynecologique. Cas no 2: tumeur trophoblastique du site d’implantation placentaire. Ann. Pathol. 2012; 32: 189–193. PubMed Abstract | Publisher Full Text\n\nBaergen RN, Rutgers JL, Young RH, et al.: Placental site trophoblastic tumor: a study of 55 cases and review of the literature emphasizing factors of prognostic significance. Gynecol. Oncol. 2006; 100: 511–520. PubMed Abstract | Publisher Full Text\n\nMarchand F: Uber die sogenannten “decidualen” geschwulste im Anschlus an normale Gebart, Abort, Blasenmole und Extrauterine Schwangerschaft. Monatsschr Geburtshilfe Gynaekol 1985; 1: 419–438.\n\nScully RE, Young RH: Trophoblastic pseudotumor. A reappraisal. Am. J. Surg. Pathol. 1981; 5: 75–76. PubMed Abstract | Publisher Full Text\n\nMardi K, Kaushal V: Placental site trophoblastic tumor - a challenging, rare entity. Taiwan. J. Obstet. Gynecol. 2010; 49: 533–535. PubMed Abstract | Publisher Full Text\n\nColecchi C, Partemi S, Minelli N, et al.: Placental site trophoblastic tumor with lung metastases as cause of death in a young patient: A case report. Placenta 2011; 32: 1060–1063. PubMed Abstract | Publisher Full Text\n\nVuong PN, Guillet JL, Houissa-Vuong S, et al.: Pathologie des tumeurs trophoblastiques gestationnelles. Gynecol. Obstet. Fertil. 2000; 28: 913–926. Publisher Full Text\n\nYalinkaya A, Ali Irfan Guzel AI, Kangal K, et al.: Two cases of placental site trophoblastic tumor. Taiwan. J. Obstet. Gynecol. 2011; 50: 372–374. PubMed Abstract | Publisher Full Text\n\nSergent F, Verspyck E, Lemoine JP, et al.: Place de la chirurgie dans la prise en charge des tumeurs trophoblastiques gestationnelles. Gynecol. Obstet. Fertil. 2006; 34: 233–238. Publisher Full Text\n\nRauw L, Delbecque K, Goffin F, et al.: Atypical recurrence of a placental site trophoblastic tumor four years after hysterectomy for benign condition: Case report and review of literature. Gynecol. Oncol. Rep. 2013; 6: 36–38. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "125758",
"date": "07 Mar 2022",
"name": "Antonio Braga",
"expertise": [
"Reviewer Expertise Gestational trophoblastic disease"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear Authors and Editors,\nI would like to thank you for the opportunity to review the paper entitled: “Case Report: Placental site trophoblastic tumor revealed by a clinical pelvic abscess”, submitted to the F1000. Similarly, I would like to congratulate the authors for their interest in the topic.\nIn this case report, the authors presented a description of a PSTT presenting as abdominal abscess, reviewing the literature of this subject.\nI would like to highlight some aspects that deserve attention.\nThe authors must describe in the case report the screening for metastatic disease, to justify the decision for TAH. PSTT is always cancer, not a benign tumor as described. Nowadays we have, besides FIGO anatomical staging system as prognostic factor for PSTT surviving, the interval of last pregnancy and the initiating of treatment of 48 months.1 In the section 'Strengths and Limitations' there is a PTTT that should be corrected.\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? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": [
{
"c_id": "10429",
"date": "06 Nov 2023",
"name": "chaouki mbarki",
"role": "Author Response",
"response": "Dear reviewer, Thank you for taking the time to review our article and for your valuable feedback. I will address your comments as follows: Regarding your first comment, the patient had undergone a total abdominal hysterectomy after a thoracoabdominopelvic CT scan revealed no metastatic lesions. We have also addressed all the other issues as per your request, which you can verify in the revised version. We would greatly appreciate it if you could approve this paper now that we have made the necessary amendments. Thank you for your assistance."
}
]
},
{
"id": "159682",
"date": "19 Jan 2023",
"name": "Maria-Gabriela Aniţei",
"expertise": [
"Reviewer Expertise oncological gynecology"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nI was pleased to review the article Case Report: Placental site trophoblastic tumor revealed by a clinical pelvic abscess.\nThe methodology used by the authors is appropriate for the purpose of the study and conclusions are narrowly linked to available evidence. The title expresses clearly the content of the manuscript and highlights the importance of the study. As the authors note in Strengths and limitations, this case report is interesting since it is the first reporting of PSTT simulating a pelvic abscess. There was rapid evolution of tumor development, only 2 months after natural birth, apparently without a risk factor from her medical history. There are interesting images intraoperative and microscopy\nThe article respects the presentation algorithm that is required for a case report type article, but there is a number of medical details are missing, such as no detailed investigations (CT-scan, for example) to exclude metastases, both at the time of diagnosis and follow-up.\nIn the same direction, to improve the methodology of this study, the introduction section must be improved. It is too short, and I suggest that some information regarding diagnosis and prognosis of PSTT should be included. Likewise, Immunohistochemistry data and the FIGO score are missing from the anatomopathological presentation, this information would increase the value of the article.\nLikewise, to be more convincing, the authors could image the patient at a distance through an CT-scan exam to confirm, through this high-performance investigation, the absence of local or distant disease. These tests would help to exclude metastases, both at the time of diagnosis and follow-up, especially as the anatomical-pathological examination shows a vascular invasion.\nThe conclusion of the article could be strengthened. Although PSTTs are extremely rare worldwide, the diagnosis should be considered during the post-partum and postabortion periods if there is persistent metrorrhagia - this means that, in front of a patient with metrorrhagia and febrile syndrome that appeared early after delivery, this differential diagnosis (PSTT) must also be taken into account.\nOther points:\n\n1. It doesn't seem representative to me that pathology should be a Keywords 2. immunohistochemistry data and the FIGO score are missing from the anatomopathological presentation 3. Usually, 'PSTTs are benign tumors' – I am not agree with this affirmation 4. In figure 3- the microscopy details must be specified - is it an image of HE? , how many times is it amplified ( which objective was used?) . As the area of interest is identified in image D, I recommend that the same thing be done for the other images (Figure 3- A, B, C, E)\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? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/11-129
|
https://f1000research.com/articles/13-843/v1
|
29 Jul 24
|
{
"type": "Research Article",
"title": "Prevalence, Characteristics and Risk Factors Analysis of Prediabetes: A Cross-Sectional Study",
"authors": [
"Rina Amelia",
"Juliandi Harahap",
"Hendri Wijaya",
"M. Aron Pase",
"Sry Suryani Widjaja",
"Saktioto Saktioto",
"Juliandi Harahap",
"Hendri Wijaya",
"M. Aron Pase",
"Sry Suryani Widjaja",
"Saktioto Saktioto"
],
"abstract": "Background Prediabetes, a reversible condition before the onset of diabetes, is a significant concern in healthcare globally. The global prediabetes epidemic has emerged and has considerably impacted health expenditures. Various risk factors play important roles in the progression of prediabetes to diabetes. Intensive lifestyle and pharmacological interventions can significantly reduce the risk of diabetes progression.\n\nObjective This study aimed to determine the prevalence, characteristics, and risk factors of prediabetes state of Medan in August 2023.\n\nMethods The sample consisted of 89 participants. This was an analytical cross-sectional study in the community that met the inclusion and exclusion criteria. The determination of prediabetes is based on the results of blood tests, namely, the examination of fasting blood sugar levels (FBGL), 2-hour postprandial oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1C). Other examinations included lipid profiling (total cholesterol, HDL-C, LDL-C, and triglycerides). Data processing was performed using SPSS via univariate and bivariate analyses (chi-square test).\n\nResults Of the 89 participants, the prevalence of prediabetes based on HbA1c, FBGL and 2-hours OGTT levels was 28.1%, 50.6%, and 28.1%, respectively. 82% of the participants were female, and 53.9% were overweight or obese based on body mass index (BMI). The risk factors related to the prevalence of prediabetes were HbA1c level, impaired FBGL, and impaired 2-hours OGTT. Other risk factors such as age, sex, daily exercise, diet, BMI, waist-hip ratio, acanthosis nigricans, lipid profile, and blood pressure did not correlate significantly with the risk factors (p>0.05).\n\nConclusion This study found that the prevalence of prediabetes was 67.4% in Medan, 82% of the participants were female, and more than 50% of participants were overweight or obese. HbA1c, FBGL, and 2-hour postprandial OGTT were the most important risk factors for prediabetes.",
"keywords": [
"macrovascular complication",
"HbA1c",
"diabetes type 2",
"Prediabetes",
"Risk Factors"
],
"content": "Introduction\n\nDiabetes is a group of metabolic diseases and a serious, long-term (chronic) condition which characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.1–3 Based on the 10th edition of the International Diabetic Federation (IDF) Atlas, the prevalence of diabetes is estimated to be 537 million adults aged 20–79 years worldwide (10.5%). This includes both type 1 and type 2 diabetes as well as diagnosed and undiagnosed diabetes. The adult population with diabetes aged between 20-79 years is estimated to be 19,465,100 in Indonesia. Instead, the prevalence of diabetes among the ages–20-79 years is 10.6% (of the total adult population aged 20-79 years is 179,720,500). In other words, one in nine people in Indonesia had diabetes.2 T2DM is one of the most important causes of morbidity and mortality worldwide.4\n\nPrediabetes is a condition that results in high BGL and often leads to T2DM.5 People with prediabetes have high BGL (are below the amount needed to be diagnosed with diabetes, but they are at a higher risk of getting diabetes.6 According to the World Health Organization (WHO), prediabetes is an intermediate level of high blood sugar. They use two specific tests to define it: impaired FBGL, which means BGL of 6.1 to 6.9 mmol/L (110–125 mg/dL) before a meal, or impaired OGTT, which mean OGTT of 7.8 to 11.0 mmol/L (140–199 mg/dL) two hours after eating 75 g of oral glucose.7\n\nAccording to the American Diabetes Association (ADA), the criterion for identifying impaired FBGL between 5.6 and 6.9 mmol/L (100-125 mg/dL), impaired OGTT between 7.8 and 11.0 mmol/L (140-199 mg/dL), and HbA1c levels between 5.7% and 6.4% (39-47 mmol/mol).8,9 Both definitions rely on FBGL measurements, 2-hour plasma glucose concentrations during an OGTT, and HbA1c concentrations.10 In Indonesia, the diagnostic criteria for prediabetes align with those established by the ADA.11 The significance of Impaired FBGL and impaired 2-hour postprandial OGTT is threefold: they signal an elevated chance of developing T2DM in the future, indicative of an existing heightened risk of cardiovascular disease (CVD), and identifying therapies that can prevent the onset of T2DM.2\n\nIndividuals with Impaired FBGL and impaired OGTT are at a high risk of developing T2DM, with up to 50% within five years.8,9 Untreated T2DM for a prolonged time can lead to complications such as retinopathy, neuropathy, CVD, or stroke.12–14 These chronic implications contribute to diabetes distress and health expenditures.15,16 Diabetes distress is a hidden emotional burden in DM.17 Healthcare expenditure for people with diabetes is expected to reach 1,054 billion USD by 2045.18 The cost of managing individuals with T2DM and complications is two times higher than that for individuals without complications.19,20\n\nRisk factors for prediabetes include BMI, waist circumference, ethnicity, family history, and sex.2,9,21 Other risk factors include hypertension, low levels of HDL cholesterol, smoking, and low levels of education and income.22 According to the RISKESDAS (National Basic Health Research) Indonesia, the increase in diabetes data is in line with the rise in obesity rates, a risk factor for diabetes, from 14.8% to 21.8% in 2013-2018. In addition, it is also in line with the increase in BMI from 11.5% to 13.6% and central obesity from 26.6% to 31%.23,24 Intensive lifestyle and pharmacological intervention can significantly reduce the risk of progression to diabetes in patients with impaired FBGL or Iimpaired OGTT.25,26\n\nThis study aimed to investigate the prevalence, characteristics, and risk factors for prediabetes in Medan, Indonesia.\n\n\nMethods\n\nA cross-sectional study of a community that fulfilled the eligibility criteria was conducted in Medan, Indonesia. The participants were people who were at least 18 years old. Participants who had been diagnosed with diabetes or were pregnant were excluded criteria. A day before the study, all participants were reminded to fast for 8 hours and were only allowed to drink plain water before we assessed their FBGL. The minimum number of participants was determined using the Slovin formula. This formula allows calculation of the minimum sample size based on an acceptable margin of error.27\n\nData were collected in August 2023 in Medan, Indonesia. Participation in this study is voluntary; participants are not obligated to participate. Earlier, the researcher provided an explanation regarding the ongoing research and their active participation in it. Subsequently, patients who gave their consent would sign the informed consent form. Participants then provided their background information, physical activity, consumption of vegetables or fruits, and history of high blood glucose (during pregnancy or medical checkups). Physical activity is defined as physical activity during work or leisure time (including daily activities) for at least 30 min. We also obtained information about a nigricans to identify additional risk factors for prediabetes. The study instrument was filled in by the participants themselves, followed by the measurement of their height, weight, waist circumference, hip circumference, systolic and diastolic blood pressure (SBP and DBP), lipid profile, FBGL, HbA1c, and 2-hour postprandial OGTT levels.\n\nThe research design was approved by the Ethics Committee of the Faculty of Medicine, Universitas Sumatera Utara. The approval number is 896/KEPK/USU/2023 (Approval date: 21 August 2023). Patient participation is voluntary; patients have no compulsion to participate in this research. Previously, the researcher explained the research protocol that would be carried out. If the patient agreed, they signed informed consent.\n\nBody Height, body weight, waist circumference, and hip circumference were measured by trained research assistants. While weighing, we asked participants to take off their footwear and only wear loose clothing. Waist circumference and hip circumference were measured using a non-stretchable tape. Patients were defined as centrally obese if they had a waist circumference of >90 cm in men and >80 cm in women. The blood pressure was measured using a digital blood pressure monitor (Omron™). FBGL, HbA1c, and 2-hour postprandial OGTT levels were measured using venous blood. The process of collecting blood was conducted in two distinct phases. The initial phase was conducted following an 8-hour fasting period by the patient, the examination included measuring the patient’s FBGL, HbA1C, and lipid profile. Subsequently, the patient was administered 75 grams of glucose (sugar dissolved in water) for the OGTT assessment, and the 2 hours post-prandial was monitored. The lipid profile was checked using the enzymatic colorimetric method (Thermo Scientific™ Indiko™ Plus Clinical Chemistry Analyzer).28 The hexokinase method (NIPRO Premier S Blood Glucose Monitoring System GM01IAA) was used to find the FBGL and 2-hour post-meal OGTT levels.29 High-performance liquid chromatography (HPLC) was used to determine HbA1c levels (BIORAD D-10 Hemoglobin Testing System).30\n\nWe conducted univariate analysis to determine the prevalence and demographic characteristics. Bivariate analysis was used to analyze the risk factors for prediabetes in Medan, Indonesia, using the Chi Square Test (p<0.05). Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS Inc.).\n\n\nResults\n\nTable 1 shows that the majority of the 89 participants were housewives (69.7%) and women (82%). 40.4 Of the participants, 40.4% had a high school education, 31.5% were age range–45-54 years old, 56.2% were never engaged in physical activity, and 51.7% consumed vegetables/fruits.\n\nA total of 25 people had prediabetes based on HbA1c measurement, 45 had prediabetes based on FBGL measurement, and 25 had prediabetes based on 2-hour postprandial OGTT levels measurement. The prevalence of prediabetes based on HbA1c, FBG, and 2-hour postprandial OGTT was 28.1%, 50.6%, and 28.1%, respectively (Table 2).\n\nTable 3 shows the waist-hip circumference ratio: 66 participants (74.2%) were obese. Based on the blood pressure examination, the median systolic and diastolic blood pressures were 142 and 86 mmHg, respectively. Based on laboratory results, the median serum total cholesterol, HDL, triglycerides levels were 206 mg/dL, 53 mg/dL, 125 mg/dL respectively.\n\nAs shown in Table 4, the risk factors for prediabetes were significantly correlated if the p-value was <0.05. According to the chi-square analysis, there was no significant relationship between risk factors, such as age, sex, daily exercise, consumption of vegetables/fruits, BMI, HDL, LDL, triglyceride, total cholesterol, acanthosis nigricans, and systolic and diastolic blood pressure in prediabetes patients. Meanwhile, risk factors, including HbA1c, FBGL, and 2-hours postprandial OGTT, have a significant relationship with prediabetes.\n\n* Statistical significance (p<0.05).\n\n\nDiscussion\n\nOur study demonstrated that the prevalence of individuals with prediabetes in Medan, Indonesia, using HbA1c, FBGL, and 2-hours postprandial OGTT were 28.1%, 50.6%, and 28.1%, respectively. The prevalence of prediabetes based on FBGL examinations in 33 provinces in Indonesia was 10%.31 In this study, the prevalence of prediabetes using FBGL was one-fifth of that in the previous study. Another study found that the prevalence of prediabetes in Pontianak with an FBGL > 100 mg/dL was 76.5%. A significant increase in the prevalence of prediabetes has also been reported in the US, Europe, North America, the Caribbean, Africa, West Iran, and Malaysia.32,33 The global prevalence of prediabetes using FBGL and 2-hours postprandial OGTT is estimated to increase to 6.5% and 10%, respectively, in 2045.8\n\nIn this study, we found that most patients with prediabetes were 55-64 years old. Similar to the study by Andriani et al., the majority of prediabetic patients were > 50 years old. However, in this study, age was not significantly correlated with the incidence of prediabetes. A previous study found a significant relationship between age and incidence of prediabetes (p=0.029).22 Numerous additional factors that may impact the etiology of prediabetes are also associated with advanced age. Peripheral insulin resistance is increasing in tandem with these processes. with a poor diet, little exercise, or obesity. Hyperglycemia results if this process occurs in people who are at risk of developing prediabetes. The degree of environmental exposure and lifestyle choices have a significant impact on the rate and timing of development.22\n\nThe frequency of physical inactivity in the subjects diagnosed with prediabetes in this study was 37.1% (p= 0.925). This contradicts the claim that a sedentary lifestyle influences the development of prediabetes and diabetes. Exercise helps to avoid obesity and increases insulin sensitivity. Compared to people who exercise, those who do not exercise may be more susceptible to developing prediabetes and diabetes.34 Our study showed that there was no correlation between physical activity, diet, hyperlipidemia, and prediabetes. This study is in accordance with previous studies that stated that physical activity, diet, and hypercholesterolemia had no relationship with the incidence of prediabetes. Although physical activity is known to be protective against the onset of type 2 diabetes,35 Redondo et al.36 did not find a correlation between prediabetes and noncompliance with the WHO physical activity guidelines. Similar results have been obtained in other investigations.\n\nIn this study, we found that most patients with prediabetes were female, overweight, or obese. This study is consistent with research conducted in Pontianak, showing that female and overweight or obesity are more prevalent among people with prediabetes.22 However, in this study, we found that sex and BMI were not significantly correlated with the incidence of prediabetes.\n\nAnother study showed that sex and BMI were associated with prediabetes. Premenopausal women with prediabetes are prone to cardiometabolic risk factors and a threefold risk of obesity and central obesity.37 Our study showed that 82% of the respondents were women. Women of reproductive age are less susceptible to cardiovascular disease because of the protective effects of estrogen. Estrogen commonly reduces triglyceride and LDL-C circulating levels, while increasing HDL-C levels. However, some studies have mentioned the development of cardiovascular disease in women with lower blood glucose levels than in men.38–40 The mean BMI in this study was 26.61 (95% CI 25.53-27.68). BMI is a risk factor for prediabetes. BMI is a simple anthropometric measure commonly used to measure general adiposity.37 Asian populations have more visceral fat than Caucasian populations do. This results in metabolic disorders, lipotoxicity, and insulin resistance. In addition, limited insulin secretory capacity and genetic predisposition play important roles in the development of insulin resistance. Several studies have reported that there is no relationship between BMI and the obesity paradox, and BMI acts as a simple indicator for evaluating the risk of blood glucose and lipid metabolism.41 Maintaining a normal weight BMI is essential in the education of patients with prediabetes and is a concern for physicians.42\n\nIn this study, of 16 risk factors, only 3 risk factors have significant correlation with prediabetes in Medan (p<0.05), namely HbA1c, IFG, and IGT. The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as having a fasting plasma glucose (FPG) level of 100–125 mg/dL, impaired glucose tolerance (IGT) as having a 2-hour postprandial glucose of 140–199 mg/dL, or elevated HbA1c (5.7%–6.4%) as having “prediabetes,” or intermediate hyperglycemia, and advises this population to make preventative efforts. Similar to the study by Barry et al., the majority of prediabetic participants in their sample showed elevated HbA1c (51%), IFG (67%), and IGT (32%) was significantly lower.43 This is a new finding that has never been published in this manner: women are significantly more likely than males to have elevated HbA1c levels.\n\nWomen are more likely than men to have increased HbA1c readings, which is a novel finding not previously documented in this manner. There was a substantial difference in the joint distribution of IGT, IFG, and elevated HbA1c values between men and women. Statistics suggest that the specific definition of prediabetes used can significantly impact the percentage of women and men who are classified as having prediabetes and are eligible for targeted lifestyle treatments to prevent diabetes. However, the exact reason for this observation is still unclear.40\n\nPreventing T2DM provides significant public health benefits, including lower rates of complications.44 Implementing lifestyle counselling in clinical practice is feasible and cost-effective.45 Program-intensive lifestyle interventions from the DPP were to achieve and maintain a minimum weight loss of 7% and a physical activity of 150 min per week identical in intensity to brisk walking. The goal of physical activity was to approximate at least 700 kcal/week of physical activity.46 The 12-week intervention consisted of four nutrition visits and instructions on a high-carbohydrate diet (60% to 70% daily calories), high-fiber diet, and low-fat diet (<7% calories from saturated fat). The results showed 5% weight loss.44 In a study of participants at a high risk of diabetes, dietary fiber intake lowered postprandial blood glucose and insulin resistance. The recommended dietary fibre intake recommendation is 3.0 g or 1,000 kcal of total energy per day to prevent T2DM.16 Holistic and integrated coordination is needed to assess the disease, including early detection in high-risk factor populations, targeted treatment, and intensive lifestyle modification.\n\n\nConclusion\n\nThis study found that The prevalence of prediabetes in the Medan group was 67.4%. 82% of the participants were female, and more than half were overweight or obese based on body mass index. Risk factors such as HbA1c, IFG, and IGT were significantly correlated with the incidence of prediabetes in Medan. Early detection is necessary to assess high-risk factors, targeted treatment, and intensive lifestyle modifications.\n\nThe research design was approved by the Ethics Committee of the Faculty of Medicine, Universitas Sumatera Utara. The approval number is 896/KEPK/USU/2023 (Approval date: 21 August 2023). Patient participation is voluntary; patients are not compelled to participate in this research. Before being included in the research, patients are given an informed consent sheet containing information about research procedures, blood examinations, the discomfort they will experience when taking blood, and other matters related to the research. If the patient understands and is willing to participate, they must sign the informed consent sheet.",
"appendix": "Data availability\n\nFigshare: Prediabetes data, https://doi.org/10.6084/m9.figshare.25612098.v1. 47\n\nThis project contains the following underlying data:\n\n• Data file: Prediabetes Data\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nKharroubi AT, Darwish HM: Diabetes mellitus: The epidemic of the century. World J. Diabetes. 2015; 6(6): 850–867. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMagliano DJ, Boyko EJ: IDF Diabetes Atlas 10th edition scientific committee. IDF Diabetes Atlas. 10th ed.Brussels: International Diabetes Federation; 2021\n\nAmelia R, Harahap J, Zulham, et al.: Educational Model and Prevention on Prediabetes: A Systematic Review. Curr. Diabetes Rev. 2024; 20: e101023221945. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLee CMY, Colagiuri S, Woodward M, et al.: Comparing different definitions of prediabetes with subsequent risk of diabetes: an individual participant data meta-analysis involving 76 513 individuals and 8208 cases of incident diabetes. BMJ Open Diabetes Res. Care. 2019; 7(1): e000794. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVicks WS, Lo JC, Guo L, et al.: Prevalence of prediabetes and diabetes vary by ethnicity among U.S. Asian adults at healthy weight, overweight, and obesity ranges: an electronic health record study. BMC Public Health. 2022; 22(1): 1954. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhan RMM, Chua ZJY, Tan JC, et al.: From Pre-Diabetes to Diabetes: Diagnosis, Treatments and Translational Research. Medicina (Kaunas). 2019; 55(9): 546. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBansal N: Prediabetes diagnosis and treatment: A review. World J. Diabetes. 2015; 6(2): 296–303. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRooney MR, Fang M, Ogurtsova K, et al.: Global Prevalence of Prediabetes. Diabetes Care. 2023; 46(7): 1388–1394. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmerican Diabetes Association: 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021; 44(Supplement1): S15–S33. PubMed Abstract | Publisher Full Text\n\nBeulens J, Rutters F, Rydén L, et al.: Risk and management of pre-diabetes. Eur. J. Prev. Cardiol. 2019; 26(2): 47–54. Publisher Full Text\n\nSoelestijo S, Sanusi H, Sasiarini L, et al.: Pedoman Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 Dewasa di Indonesia. Indonesia: PB PERKENI; 2021.\n\nAmelia R, Sari Wahyuni A, Yunanda Y, et al.: Atherosclerotic Cardiovascular Disease in Diabetes Patients. Curr. Diabetes Rev. 2023; 19(8): e060223213457. Publisher Full Text\n\nAmelia R, Wijaya H, Rusdiana R, et al.: Risk of Cardiovascular Complication Among Type 2 Diabetes Mellitus Patients in Medan, Indonesia. A Cross-sectional Study. Med. Arch. 2022 Oct; 76(5): 324–328. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmelia R, Harahap J, Lelo A, et al.: Risk analysis for cardiovascular complication based on the atherogenic index of plasma of type 2 diabetes mellitus patients in Medan, Indonesia. Family Med. Prim. Care Rev. 2020; 22(3): 197–201. Publisher Full Text\n\nHostalek U: Global epidemiology of prediabetes - present and future perspectives. Clin. Diabetes Endocrinol. 2019; 5: 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFeldman EL, Callaghan BC, Pop-Busui R, et al.: Diabetic neuropathy. Nat. Rev. Dis. Prim. 2019; 5: 42. Publisher Full Text\n\nAmelia R, Sahbudin D, Yamamoto Z: Stress level and self-concept among type 2 diabetes mellitus patients in Indonesia. Family Med. Prim. Care Rev. 2020; 22(2): 111–115. Publisher Full Text\n\nSun H, Saeedi P, Karuranga S, et al.: IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res. Clin. Pract. 2022; 183: 109119. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHidayat B, Ramadani RV, Rudijanto A, et al.: Direct Medical Cost of Type 2 Diabetes Mellitus and Its Associated Complications in Indonesia. Value Health Reg. Issues. 2022; 28: 82–89. PubMed Abstract | Publisher Full Text\n\nAmelia R: The Model of Self Care Behaviour and the Relationship with Quality Of Life, Metabolic Control and Lipid Control of Type 2 Diabetes Mellitus Patients in Binjai City, Indonesia. Open Access Maced. J. Med. Sci. 2018 Sep 21; 6(9): 1762–1767. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmelia R, Harahap J, Wijaya H: The role of physical activity on glucose transporter-4, fasting blood glucose level and glycate hemoglobin in type 2 diabetes mellitus patients in Medan, Indonesia. Family Med. Prim. Care Rev. 2021; 23(3): 274–278. Publisher Full Text\n\nBudiastutik I, Kartasurya MI, Subagio HW, et al.: High Prevalence of Prediabetes and Associated Risk Factors in Urban Areas of Pontianak, Indonesia: A Cross-Sectional Study. J. Obes. 2022; 2022: 4851044–4851049. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKementerian Kesehatan Republik Indonesia: InfoDATin 2020 Diabetes Melitus. Pusdatin.2020\n\nAmelia R, Burhan B, Lelo A: The Relationship between Anthropometry and Ankle-Brachial Index with Blood Glucose Level in Patients with Type 2 Diabetes Mellitus at Community Health Center in Medan, Indonesia. Family Med. Prim. Care Rev. 2018; 20(4): 307–312. Publisher Full Text\n\nAmelia R, Lelo A, Lindarto D, et al.: Analysis of factors affecting the self-care behaviors of diabetes mellitus type 2 patients in Binjai, North Sumatera-Indonesia. Asian J. Microbiol., Biotechnol. Environ. Sci. 2018; 20(2): 361–367.\n\nRusdiana SM, Amelia R: The Effect of Diabetes Self-Management Education on Hba1c Level and Fasting Blood Sugar in Type 2 Diabetes Mellitus Patients in Primary Health Care in Binjai City of North Sumatera, Indonesia. Open Access Maced. J. Med. Sci. 2018 Apr 12; 6(4): 715–718. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAnoyke MA: Sample Size Determination in Survey Research. J. Sci. Res. Rep. 2020; 26(5): 90–97. Publisher Full Text\n\nKathak RR, Sumon AH, Molla NH, et al.: The association between elevated lipid profile and liver enzymes: a study on Bangladeshi adults. Sci. Rep. 2022; 12(1): 1711. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSonagra A, Zubair M, Motiani A: Hexokinase method. StatPearls; 2024.\n\nZechmeister B, Erden T, Kreutzig B, et al.: Analytical interference of 33 different hemoglobin variants on HbA1c measurements comparing high-performance liquid chromatography with whole blood enzymatic assay: a multi-center study. Clin. Chim. Acta. 2022; 531: 145–151. PubMed Abstract | Publisher Full Text\n\nSoewondo P, Pramono LA: Prevalence, Characteristics, and Predictors Of Pre-diabetes In Indonesia. Med. J. Indones. 2011; 20(4): 283–294. Publisher Full Text\n\nCenter for Disease Control and Prevention: Prevalence of Prediabetes Among Adults. The United States of America (The US): CDC; 2022 [updated 2022; cited 2023 Sept 06]. Prevalence of Prediabetes Among Adults|Diabetes|CDC.\n\nAkhtar S, Nasir JA, Ali A, et al.: Prevalence of type-2 diabetes and prediabetes in Malaysia: A systematic review and meta-analysis. PLoS One. 2022; 17(1): e0263139. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAndriani RN, Fitriadi Y, Danawati CW, et al.: Analysis of prediabetes risk factors at primary health care centers. RevPrim. Care Prac. Educ. 2022; 5(2): 52–56. Publisher Full Text\n\nGalaviz KI, Narayan KMV, Lobelo F, et al.: Lifestyle and the Prevention of Type 2 Diabetes: A Status Report. Am. J. Lifestyle Med. 2018; 12(1): 4–20. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRedondo AD, et al.: Modifiable risk factors associated with prediabetes in men and women: a cross-sectional analysis of the cohort study in primary health care on the evolution of patients with prediabetes (PREDAPS-Study). BMC Fam. Pract. 2015; 16(5): 5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYoshida Y, Jia W, Yuanhao Z, et al.: Rising Prediabetes, Undiagnosed Diabetes, and Risk Factors in Young Women. Am. J. Prev. Med. 2023; 64(3): 423–427. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBernabe-Ortiz A, Perel P, Miranda JJ, et al.: Diagnostic accuracy of the Finnish Diabetes Risk Score (FINDRISC) for undiagnosed T2DM in Peruvian population. Prim. Care Diabetes. 2018; 12(6): 517–525. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSiddiqui S, Zainal H, Harun SN, et al.: Gender differences in the modifiable risk factors associated with the presence of prediabetes: A systematic review. Diabetes Metab. Syndr. Clin. Res. Rev. 2020; 14(5): 1243–1252. PubMed Abstract | Publisher Full Text\n\nRao G, Powell-Wiley TM, Ancheta I, et al.: Identification of obesity and cardiovascular risk in ethnically and racially diverse populations: a scientific statement from the american heart association. Circulation. 2015; 132(5): 457–472. PubMed Abstract | Publisher Full Text\n\nChai Y, Liu Y, Yang R, et al.: Association of body mass index with risk of prediabetes in Chinese adults: A population-based cohort study. J. Diabetes Investig. 2022; 13(7): 1235–1244. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGrundlingh, et al.: Assessment of prevalence and risk factors of diabetes and pre-diabetes in South Africa. J. Health Popul. Nutr. 2022; 41(7): 7. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGreiner GG, Emmert-Fees KMF, Becker J, et al.: Toward targeted prevention: risk factors for prediabetes defned by impaired fasting glucose, impaired glucose tolerance and increased HbA1c in the population-based KORA study from Germany. Acta Diabetol. 2020; 57: 1481–1491. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLipsombe L, Booth G, Butalia S, et al.: Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada: Pharmacologic Glycemic Management of Type 2 Diabetes in Adults. Can. J. Diabetes. 2018; 42(Suppl 1): S88–S103. Publisher Full Text\n\nMoradpour F, Rezaei S, Piroozi B, et al.: Prevalence of prediabetes, diabetes, diabetes awareness, treatment, and its socioeconomic inequality in west of Iran. Sci. Rep. 2022; 12(1): 17892. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmerican Diabetes Association: Standards of Medical Care in Diabetes—2020 Abridged for Primary Care Providers. Clin. Diabetes. 2020; 38(1): 10–38. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmelia R: Prediabetes Data.Publisher Full Text"
}
|
[
{
"id": "313859",
"date": "30 Aug 2024",
"name": "Hanaa Reyad Abdallah",
"expertise": [
"Reviewer Expertise Child growth and development",
"Diabetes",
"NAFLD",
"Obesity",
"nutrition",
"stunted growth",
"Autism",
"Down Syndrome",
"Oxidative stress",
"Gut microbiota."
],
"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 gives information about the prevalence of pre-diabetes in Medan state in Indonesia which was diagnosed by three methods; HbA1c, OGTT and FBG. the authors also investigated factors associated with pre-diabetes occurrence in those people. Here are my comments about this manuscript: 1- The title: please remove the word \"analysis\". 2- Methods: - I think the sample size is small for a community based study representing a state like Medan. - The anthropometric measures needs to be in more details and reference is needed and BMI calculation and classification is shoes insufficiency. - The statistical analysis: the statistical tests were not used appropriately as follows: - The Chi square test is not used to detect associated factors; it is used to compare two groups according to qualitative data. so you should calculate the percentages in each group ( prediabetes group and normal group) separately. - The correlation was not assessed accurately as you should use the tests of correlation e.g Pearson's correlation coefficient test. - The risk factors associated with the occurrence of prediabetes should be assessed by Multiple logistic regression analysis not Chi square test. 3- Results: - The prevalence of prediabetes was mentioned by three percentages according to the method used to diagnose it then latter in the text it was mentioned in only one percentage which differed completely from these findings. - there is discrepancies in results in the tables than those in the text so please revise your results accurately. - HbA1c, FBGL, and 2-hours postprandial OGTT, are not risk factors for prediabetes, they are diagnostic tests used to detect prediabetes. 4- The conclusion: the prevalence of prediabetes mentioned was completely different than this in the results. 5-The legends of tables contains some abbreviations which was not present in the tables as IGF1 & VEGF.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "317377",
"date": "18 Sep 2024",
"name": "Rajendra Pradeepa",
"expertise": [
"Reviewer Expertise Epidemiology of diabetes and associated complications"
],
"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 asking me to review the article entitled “Prevalence, Characteristics and Risk Factors Analysis of Prediabetes: A Cross-Sectional Study” conducted in Medan, Indonesia. The study aimed to determine the prevalence, characteristics, and risk factors of prediabetes state of Medan in August 2023 among 89 participants. The authors have reported the prevalence of prediabetes based on HbA1c, FBG and 2-hours OGTT levels as 28.1%, 50.6%, and 28.1%, respectively. They have provided the clinical and biochemical characteristics and risk factors assessed in the study population. The study has been conducted in one month with a very small sample size of 89 participants. The authors could also assess the prevalence using combinations of criteria such as using both HbA1c and FBG etc. The statistical analysis done is very basic, suggest to include multivariate regression to assess the association of risk factors with prediabetes.\nThis manuscript needs major modification\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? No\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-843
|
https://f1000research.com/articles/13-1261/v1
|
21 Oct 24
|
{
"type": "Research Article",
"title": "The most common neonatal presentations to the pediatric emergency department",
"authors": [
"Mohammad A AlGhamdi",
"Abdulrahman A Alnaim",
"Hassan M. Alibrahim",
"Alaa A. Aldajani",
"Muneera A.Alabdulqader",
"Mohammad A AlGhamdi",
"Hassan M. Alibrahim",
"Alaa A. Aldajani",
"Muneera A.Alabdulqader"
],
"abstract": "Introduction The first 28 days of life are considered the neonatal period, when pediatric health is most vulnerable. While crises can undoubtedly arise during this time, many ED or urgent care visits could be avoided with sufficient preventive hospital care during the newborn period and suitable follow-up with a primary care physician. The use of emergency rooms for non-urgent care could be the cause of rising healthcare costs and ineffective resource use.\n\nPurpose This study aimed to determine the presenting features, management, and disposition of neonatal attendance in the emergency department.\n\nMethods This was a retrospective observational cross-sectional study of medical records identified via the emergency department of neonatal visits (≤28 days) to King Fahd Hospital of the University (KFHU), Khobar, Saudi Arabia, over 12 months (2021–2022). The Chi-square test was performed to compare various etiologies, with a 5% significance level.\n\nResults A total of 649 neonate visited pediatric emergency department with a mean age of 15.5 ± 7.4 days and almost equal distribution of the gender. The most common presentation was upper respiratory tract infection (URTI) (26.8%), followed by physiological jaundice (20.2%), and colic (14%). A total of 205 (31.6%) neonates who visited the ED showed significant laboratory findings. Seventy-nine patients (12.2%) presenting with PED were admitted to the hospital.\n\nConclusion Healthcare systems must devise strategies to address the growing number of non-urgent visits to emergency departments in a more efficient manner, while simultaneously reallocating scarce resources to higher-acuity cases. This emphasizes the necessity of health personnel educating caregivers. It’s also critical that medical professionals understand the common ailments that affect newborns and are skilled at correctly identifying ailments that could indicate a serious pathology.",
"keywords": [
"Newborn",
"neonate",
"emergency department",
"Urgent",
"Non-urgent",
"Saudi Arabia"
],
"content": "Introduction\n\nThe emergency department is the base of any hospital providing urgent medical services to treat patients with a restricted workforce and resources. Over the past few decades, there has been an annual increase in the number of Emergency department (ED) visitors from 96.5 million to 119.2 million between 1995 and 2006. The leading consequences were significantly negative on the quality of urgent remediation by ER physicians, duration of patient waiting, and eventually poorer overall outcomes, such as increasing rates of mortality.1 Approximately 4-10% of all ED visitors are children with common complaints related to injuries and poisoning. More than 41% of children had visited the ER within their first year2–4 and 25-50% had visited more than once,5–7 and about 49-70% presenting with non-urgent matter.5 Many studies have linked a shorter neonatal hospital stay (less than 48 hours after birth) with the rate of neonates visiting the emergency department. The result showed wavering between increasing, decreasing, or no significant effects.\n\nA retrospective study that evaluated all neonates’ arrivals at a tertiary urban children’s ED showed that breathing difficulty was the most common chief complaint. Vomiting and poor feeding were defined as follows: No apparent medical problems were repeatedly diagnosed, and the most common pathological diagnoses were bronchiolitis and sepsis. Fifty percent of the visitors were self-referrals by their parents. Most of them do not require pharmacological management.8 Another retrospective study was conducted on neonate visitors to the PED of the Central de Faro Hospital in 2005. Jaundice, excessive crying, rash, nasal congestion, and cough were the common complaints. Only jaundice, fever, cough, failure to thrive, and choking preceded diagnostic tests. No medical issues, infant colics, physiological jaundice, upper respiratory infection, or pathologic hyperbilirubinemia were the top diagnoses on the list. Birth weight less than 2500 g, and TG level of less than 37 weeks are both related to more serious neonatal disease and higher admission rates. There was no apparent relationship between hospital admission and delivery mode of delivery.9\n\nA comprehensive understanding of both physiological and pathological neonatal changes, especially conditions related to jaundice and feeding difficulties, is significant for all ER providers. Additionally, Understanding the features of frequent pediatric presentations in the emergency department can help take appropriate steps to address these issues and improve the quality of healthcare.\n\n\nMethods\n\nThis research aimed to determine the presenting features, management, and disposition of neonatal attendance to the emergency department.\n\nAs emergency department visits rise, healthcare organizations must devise techniques to cope with non-urgent emergency room visits more effectively while focussing scarce resources on higher-acuity situations. This emphasizes the importance of caretaker education by health professionals. It is also critical that physicians are aware of the most common illnesses in the neonatal period and understand how to accurately detect symptoms associated with a severe pathology.\n\nThis was a retrospective observational cross-sectional study of medical records identified via the emergency department of neonatal visits (≤28 days) to King Fahd Hospital of the University (KFHU), Khobar, Saudi Arabia over 12 months (2021–2022). The Chi-square test was performed to compare various etiologies, with a 5% significance level.\n\n\n\n- The patients were presented to the emergency department\n\n- Neonatal period (less than 28 days)\n\n\n\n- Age: older than 28 days old\n\n- Neonate that referred from another hospital\n\nData were collected from the medical records and ED data registry of King Fahd Hospital of the University (KFHU), Khobar, Saudi Arabia, between 2021 and 2022. Biographical information, basic laboratory investigations, outcomes in the form of admission or discharge, and final diagnoses were collected. The Chi-square test was performed to compare various etiologies, with a 5% significance level.\n\nThe study design was approved by the Institutional Review Board of King Fisal University, Al Ahsa Saudi Araia on 08-11-2022, which waived the requirement for obtaining informed consent from the ethical No. KFU-REC-2022-NOV-ETHICS306. The participants’ information was kept confidential and anonymous.\n\nFollowing data extraction, they were edited, coded, and entered into IBM SPSS version 22, a statistical program (SPSS, Inc. Chicago, IL). Two-tailed tests were used for all statistical analyses. P was set lower than 0.05. For all categorical variables, descriptive analysis utilizing frequency and percentage distribution was carried out; for numerical variables, the mean with standard deviation was utilized for display. Neonatal data were tabulated, and their clinical diagnoses and outcomes were graphed. Crosstabulation was used to assess the distribution of clinical diagnosis of neonates who attended the ED according to age, factors associated with laboratory findings, and factors associated with clinical outcome using Pearson’s chi-square and exact probability test for small frequencies.\n\n\nResults\n\nA total of 649 neonates attended the study hospital over a 1-year period. Neonate ages ranged from less than 1 d to 28 days, with a mean age of 15.5 ± 7.4 days. A total of 342 (52.7%) neonates were male, 330 (50.8%) were delivered at hospitals, and 319 (49.2%) were delivered at home (Table 1).\n\nClinical diagnosis of neonates who visited the ED. The most common diagnoses were upper respiratory tract infection (URTI) (26.8%), jaundice (20.2%), colic (14%), sepsis (8.6%), conjunctivitis (7.1%), acute gastroenteritis (4.8%), acute bronchitis (4.2%), and constipation (4%). UTI (0.5%), bleeding (0.5%), acute otitis media (0.3%), and clubfoot (0.2%) were the least reported diagnoses (Figure 1).\n\nDistribution of clinical diagnoses of neonates who attended the ED by their age. The most reported diagnoses among the early neonates were jaundice (70.8%) and colic (5.6%). Among neonates aged 7-14 days, the most reported diagnoses were jaundice (24.7%) and colic (12.4%), in addition to URTIs (18%). Among the other neonates, URTIs and colic were the most common diagnoses (Table 2).\n\nLaboratory findings among neonates who attended the ED. A total of 205 (31.6%) neonates who attended the ED had significant laboratory findings, while 443 (68.4%) had normal laboratory results (Figure 2).\n\nClinical outcome among neonates who attended the ED. Only 79 (12.2%) of the attended neonates required hospital admission, while most of them (87.8%; 570) were discharged after being managed (Figure 3).\n\nFactors associated with laboratory findings among study neonates who attended the ED. Approximately 70.8% of neonates in their first week of life had significant laboratory findings versus 16.3% of others aged 21-28 days with statistically significant differences (P=.001). In addition, significant laboratory findings were reported among 35.8% of male neonates compared to 27% of female neonates (P=.017). A total of 83.2% of neonates diagnosed with jaundice had significant laboratory findings compared to 72.7% of those with seizures, 66.7% of neonates with bleeding, and 60.7% of those with sepsis, while 6.3% of neonates with URTI showed significant laboratory findings (P=.001) (Table 3) (extended data).\n\nFactors associated with clinical outcomes among study neonates who attended the ED. A total of 25.8% of neonates below the age of 7 days required admission compared to 7.1% of older neonates (P=.001). In addition, 54.5% of neonates with seizures required admission compared to 40.7% of those with acute bronchiolitis (P=.001). A total of 38% of neonates with significant laboratory findings required hospital admission in comparison to only 1 (0.2%) with normal findings (P=.001) (Table 4) (Extended data).\n\n\nDiscussion\n\nThe first 28 days of a child’s life, also known as the neonatal period, is a crucial period for their health.10 While emergencies can occur during this time, many visits to the emergency department or urgent care can be avoided with proper preventive care during the newborn period and regular check-ups with primary care provider.11 Using emergency departments for non-urgent issues can result in higher costs and inefficient use of healthcare resources.11,12\n\nResearch has demonstrated that a significant percentage (up to 60%) of emergency department visits for infants in their first three months of life are non-urgent. This disproportionate use of emergency services is more common among younger and non-White mothers.13 Additionally, a study found that babies born to single mothers who did not attend prenatal classes were less likely to be admitted to the hospital after an ED visit, indicating that these visits may not have been necessary and could have been addressed in a primary care setting.14 However, most studies on ED use in infancy have been limited to single-center or healthcare system studies, except for a few state-based studies or those that cover a longer period than the first month of life.15–19\n\nThe current study aimed to assess the main presentations in pediatric emergency, including characterizing the presenting features, management, and disposition of neonatal attendance to a tertiary children’s ED. The study revealed that most neonates with ED attendance were aged two weeks or more and a few percent were in their first week of life. Gender differences were not dominant among study neonates and the place of delivery, with a slight predominance for males who delivered at home. Similarly, Batu ED et al.20 documented that the mean age for neonates who visited ED was 14.1 ± 8.3 days, with a slight predominance of males (57.3%). Additionally, Lim JM et al.21 found that 79.4% of patients presented at less than 15 days after birth. The length of stay in the PED was less than four hours in 94.0% of the neonates. There are conflicting results regarding the effects of early neonatal discharge on PED utilization reported in different studies.22–27\n\nWith regard to the most reported clinical diagnoses for visiting the ED among neonates, the current study showed that upper respiratory tract infection (URTI), Jaundice, Colic, and Sepsis were the most dominant. UTI, Bleeding, Acute otitis media, and clubfoot were the least reported diagnoses. The study also showed that the most reported diagnoses among early neonates were jaundice and colic, which were also reported among older neonates in addition to URTIs. Similar findings were reported by Batu et al.20 as the main complaints were jaundice, irritability, and vomiting, and the most common diagnoses were normal newborns, indirect hyperbilirubinemia, and colic. In addition, Calado et al.17 reported that the chief complaints were jaundice, excessive crying, and rashes. Diagnostic tests were requested in 27.2% of the cases. Millar et al.28 found that the most common complaints were jaundice, difficulty breathing, feeding problems, and irritability. The most frequent diagnoses were normal physiology, jaundice, feeding problems, and query sepsis. In addition to many other studies, jaundice, irritability, and respiratory tract infections were the main causes of visiting PED.27,29 Other causes have been reported, including feeding difficulties, mainly among older neonates.30,31\n\nThe current study also showed that about one-third of the neonates who attended the ED had significant laboratory results, and those who needed hospital admission were infrequent. Early neonates, male sex, jaundice, infection, sepsis, and seizure were the most significant factors associated with the need for hospitalization.\n\nThere were various restrictions on this study. Potential influencing factors found in prior studies, such as caregiver factors including parents’ social or educational levels, and information about some neonatal demographics (e.g., gestational age, Apgar scores, and the day of discharge from birth), were excluded from the retrospective analysis because it was based on medical records. Furthermore, we were unable to examine ED follow-ups or outpatient visits. For the non-acute neonates who were discharged home, we lacked follow-up data. It’s possible that they experienced serious issues that we were unaware of and were later admitted to another hospital.\n\n\nConclusions\n\nIn conclusion, the current study showed that PED visits were frequent among neonates. Jaundice was the dominant cause of PED visits and hospital admissions. The admission rate was higher during early life, mainly in male neonates. In addition, irrespective of high PED visits, only one out of three had significant laboratory findings, and most of the neonates were discharged. Providing better support for families to care for their babies at home or seeking alternative care may decrease non-urgent neonatal emergency department use.\n\n\nEthics and consent\n\nThe study design was approved by the Institutional Review Board of King Fisal University, Al Ahsa Saudi Araia on 08-11-2022, which waived the requirement for obtaining informed consent from the ethical No. KFU-REC-2022-NOV-ETHICS306. The participants’ information was kept confidential and anonymous.",
"appendix": "Data availability statement\n\nFigshare: neonatal presentation to ER, https://doi.org/10.6084/m9.figshare.26828059.v2. 32\n\nThis project contains the following underlying data:\n\n• Neonatal presentation to ER: cosisting of the main database\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: neonatal presentation to ER, https://doi.org/10.6084/m9.figshare.26828059.v2. 32\n\nThis project contains the following underlying data:\n\n• Tables: consisting of the results\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nHoot NR, Aronsky D: Systematic review of emergency department crowding: causes, effects, and solutions. Ann. Emerg. Med. 2008 Aug 1; 52(2): 126–136.e1. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTrzeciak S, Rivers EP: Emergency department overcrowding in the United States: an emerging threat to patient safety and public health. Emerg. Med. J. 2003 Sep 1; 20(5): 402–405. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchappert SM: Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments. United States; 1997.\n\nShah MN, Cushman JT, Davis CO, et al.: The epidemiology of emergency medical services use by children: an analysis of the National Hospital Ambulatory Medical Care Survey. Prehosp. Emerg. Care. 2008 Jan 1; 12(3): 269–276. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNawar EW, Niska RW, Xu J: National hospital ambulatory medical care survey: 2005 emergency department summary.\n\nSeidel JS, Henderson DP, Ward P, et al.: Pediatric prehospital care in urban and rural areas. Pediatrics. 1991 Oct 1; 88(4): 681–690. PubMed Abstract | Publisher Full Text\n\nKallsen G: Epidemiology of pediatric prehospital care. Ann. Emerg. Med. 1987 Mar 1; 16(3): 284–292. Publisher Full Text\n\nJoyce SM, Brown DE, Nelson EA: Epidemiology of pediatric EMS practice: a multistate analysis. Prehosp. Disaster Med. 1996 Sep; 11(3): 180–187. PubMed Abstract | Publisher Full Text\n\nSeidel JS, Hornbein M, Yoshiyama K, et al.: Emergency medical services and the pediatric patient: are the needs being met? Pediatrics. 1984 Jun 1; 73(6): 769–772. Publisher Full Text\n\nBrousseau T, Sharieff GQ: Newborn emergencies: the first 30 days of life. Pediatr. Clin. N. Am. 2006 Feb 1; 53(1): 69–84. Publisher Full Text\n\nStanley R, Zimmerman J, Hashikawa C, et al.: Appropriateness of children’s nonurgent visits to selected Michigan emergency departments. Pediatr. Emerg. Care. 2007 Aug 1; 23(8): 532–536. PubMed Abstract | Publisher Full Text\n\nUscher-Pines L, Pines J, Kellermann A, et al.: Emergency department visits for nonurgent conditions: systematic literature review. Am. J. Manag. Care. 2013 Jan 1; 19(1): 47–59. PubMed Abstract\n\nPomerantz WJ, Schubert CJ, Atherton HD, et al.: Characteristics of nonurgent emergency department use in the first 3 months of life. Pediatr. Emerg. Care. 2002 Dec 1; 18(6): 403–408. PubMed Abstract | Publisher Full Text\n\nMillar KR, Gloor JE, Wellington N, et al.: Early neonatal presentations to the pediatric emergency department. Pediatr. Emerg. Care. 2000 Jun 1; 16(3): 145–150. PubMed Abstract | Publisher Full Text\n\nSacchetti AD, Gerardi M, Sawchuk P, et al.: Boomerang babies: emergency department utilization by early discharge neonates. Pediatr. Emerg. Care. 1997 Dec 1; 13(6): 365–368. PubMed Abstract | Publisher Full Text\n\nLain SJ, Roberts CL, Bowen JR, et al.: Early discharge of infants and risk of readmission for jaundice. Pediatrics. 2015 Feb 1; 135(2): 314–321. PubMed Abstract | Publisher Full Text\n\nCalado CS, Pereira AG, Santos VN, et al.: What brings newborns to the emergency department?: a 1-year study. Pediatr. Emerg. Care. 2009 Apr 1; 25(4): 244–248. PubMed Abstract | Publisher Full Text\n\nKotagal UR, Schoettker PJ, Atherton HD, et al.: Relationship between early primary care and emergency department use in early infancy by the Medicaid population. Arch. Pediatr. Adolesc. Med. 2002 Jul 1; 156(7): 710–716. PubMed Abstract | Publisher Full Text\n\nJain S, Cheng J: Emergency department visits and rehospitalizations in late preterm infants. Clin. Perinatol. 2006 Dec 1; 33(4): 935–945. PubMed Abstract | Publisher Full Text\n\nBatu ED, Yeni S, Teksam O: The factors affecting neonatal presentations to the pediatric emergency department. J. Emerg. Med. 2015 May 1; 48(5): 542–547. PubMed Abstract | Publisher Full Text\n\nLim JM, James V, Yeo YJ, et al.: Neonatal presentations to the paediatric emergency department in Singapore. Singapore Med. J. 2022 Nov 1; 63(11): 667–673. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBoulvain M, Perneger TV, Othenin-Girard V, et al.: Home-based versus hospital-based postnatal care: a randomised trial. BJOG Int. J. Obstet. Gynaecol. 2004 Aug; 111(8): 807–813. Publisher Full Text\n\nDanielsen B, Castles AG, Damberg CL, et al.: Newborn discharge timing and readmissions: California, 1992–1995. Pediatrics. 2000 Jul 1; 106(1): 31–39. PubMed Abstract | Publisher Full Text\n\nGupta P, Malhotra S, Singh DK, et al.: Length of postnatal stay in healthy newborns and re-hospitalization following their early discharge. Indian J. Pediatr. 2006 Oct; 73: 897–900. PubMed Abstract | Publisher Full Text\n\nKennedy TJ, Purcell LK, LeBlanc JC, et al.: Emergency department use by infants less than 14 days of age. Pediatr. Emerg. Care. 2004 Jul 1; 20(7): 437–442. Publisher Full Text\n\nLutfi S, Al-Rifai H, Al-Ansari K: Neonatal visits to the pediatric emergency center and its implications on postnatal discharge practices in Qatar. J. Clin. Neonatol. 2013 Jan 1; 2(1): 14–19. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHarrold J, Langevin M, Barrowman N, et al.: Parental characteristics and perspectives pertaining to neonatal visits to the emergency department: a multicentre survey. Can. Med. Assoc. Open Access J. 2018 Jul 1; 6(3): E423–E429. Publisher Full Text\n\nMillar KR, Gloor JE, Wellington N, et al.: Early neonatal presentations to the pediatric emergency department. Pediatr. Emerg. Care. 2000 Jun 1; 16(3): 145–150. PubMed Abstract | Publisher Full Text\n\nGill PJ, Goldacre MJ, Mant D, et al.: Increase in emergency admissions to hospital for children aged under 15 in England, 1999–2010: national database analysis. Arch. Dis. Child. 2013 May 1; 98(5): 328–334. PubMed Abstract | Publisher Full Text\n\nBlakey S, Lyttle MD, Magnus D: Neonatal presentations to the children’s emergency department. medRxiv. 2020 Sep 9:2020-09.\n\nFlanagan CF, Stewart M: Factors associated with early neonatal attendance to a paediatric emergency department. Arch. Dis. Child. 2014 Mar 1; 99(3): 239–243. PubMed Abstract | Publisher Full Text\n\nAlnaim AA: Neonatal presentation to ER. figshare. [Dataset]. 2024. Publisher Full Text"
}
|
[
{
"id": "338411",
"date": "27 Dec 2024",
"name": "Nalinikanta Panigrahy",
"expertise": [
"Reviewer Expertise Neonatal care",
"ELBW care and flow up",
"HFOV ventilation",
"Neonatal transport."
],
"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\n\nits a good attempt to know use of an emergency service for neonates .\nMy suggestions will be likely 1. Justify your sample size ,is it powered for your conclusion. 2. Clearly document hospital policy as its all inborn babies which baby can seek help in emergency room and who shall avail OPD consultation . 3. Neonatal Jaundice as most common cause of ER visit and majority not requiring admission little difficult to understand. 4. A comparative analysis of any two group of populations such as inborn vs outworn, ER vs OPD consultation might have better conclusion . Best Wishes\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": []
}
] | 1
|
https://f1000research.com/articles/13-1261
|
https://f1000research.com/articles/13-1259/v1
|
21 Oct 24
|
{
"type": "Case Report",
"title": "Case Report: An exceptional localisation in the thigh of a giant primary subcutaneous hydatid cyst.",
"authors": [
"Aymen Fekih",
"Jacem Saadana",
"Firas Chaouch",
"Firas Boughattas",
"Ikram Haddada",
"Jacem Saadana",
"Firas Chaouch",
"Firas Boughattas",
"Ikram Haddada"
],
"abstract": "Hydatid disease is a zoonotic disease caused by the larval stage of Echinococcus granulosus and is found globally. Although the liver and lungs are the most prevalent sites of involvement, sub-cutaneous hydatid cysts are rare especially in the primary occurrence. Sub-cutaneous hydatid cysts usually are noticed as slow growing, painless, and mobile masses beneath the overlying skin which is usually normal and are generally found on the trunk and proximal extremities. To the best of our knowledge, very few cases of primary subcutaneous hydatid cysts of the thigh have been documented. We present a case of a 30-year-old woman from a rural setting, who has a large, painless swelling on her thigh. Imaging studies confirmed the presence of a primary subcutaneous hydatid cyst, which is an atypical presentation of the disease. The entire lesion was excised surgically without any evidence of recurrence for a long period postoperatively. This case illustrates the difficulty in establishing a diagnosis and the importance of early surgical management in these cases.",
"keywords": [
"Hydatid cyst",
"Subcutaneous",
"Primary",
"Thigh"
],
"content": "Introduction\n\nAlveolar echinococcosis is a zoonosis which is prevalent in all geographical regions of the earth, due to the infection which occurs in the development stages in humans or animals of Echinococcus granulosus.1 Most commonly, the liver and lungs are the ailing organs, and the brain follows. Such parasitic infection of primary cutaneous site of invasion is exceptionally rare and scantily available in literature.2\n\nThis study reports the case of a young woman presenting with a giant subcutaneous hydatid cyst primarily localized to the thigh, which ultimately required surgical management.\n\n\nCase report\n\nA 30-year-old female from an endemic area came with complaint of painless subcutaneous mass on right thigh.\n\nExamination findings established a firm, fixed, 20 cm diameter mass with a superficial ulcer in the overlying skin (Figure 1). This mass was discovered nine months ago and has gradually increased in size, becoming genate to walking.\n\nA magnetic resonance imaging (MRI) showed a singular large subcutaneous lesion measuring 166×120×123 mm, which possessed a daughter cyst in the middle and appeared bright in T2 weighted sequence and had peripheral enhancement after the administration of gadolinium, indicating a hydatid cyst (Figure 2).\n\nSince serology returned negative and there were no other abnormalities on assessment of other sites, primary subcutaneous hydatid cyst was diagnosed.\n\nSurgical management involved complete excision of the lesion with sufficient margins, which preserved the adductor muscle complexes (Figure 3). Despite the apposition of a tension-free primary closure, a skin defect created by the excision of the cyst was also present (Figure 4).\n\nThe diagnosis of hydatid cyst was confirmed by histological examination. Anthelmintic treatment was not undertaken, as the serological results were negative.\n\nAfter the procedure, the recovery was uncomplicated. The patient has been under observation for two years with no evidence of either local or distal recurrence.\n\n\nDiscussion\n\nHydatid disease, a parasitic infection caused by tapeworms of the genus Echinococcus is considered a serious health issue in such areas. This endemic disease caused is transmissed through ingestion of food or water likely to contain the tapeworm eggs.3\n\nMost of the hydatid cysts do develop in the liver and lungs; however, primary isolated subcutaneous localization is infrequent and accounts for rates of about 2%.4\n\nThe cause of primary subcutaneous hydatid cysts formation has not been established however, several explanations have been suggested: such as contamination of skin lesions, or eggs which have bypassed the liver and lungs, and have settled in the subcutis.5\n\nThe typical course of subcutaneous hydatid cysts is characterized by a slowly enlarging, painless and mobile mass under intact overlying skin.6\n\nIt should be noted that complications like infection or cyst rupture, while uncommon, can happen, and therefore treatment should be sought immediately.7\n\nIn contrast to visceral hydatid cysts, cysts located in the subcutaneous region scarcely enlarge inwards resulting in minimal pressure effects on adjacent parts.8\n\nImaging modalities, particularly ultrasound, play a significant role in the assessment of subcutaneous hydatid cysts. Indeed, the structure of cysts can show thick walls with daughter cysts inside, calcifications and a special germinal layer.6\n\nMRI is usually the preferred imaging modality for assessment of the soft tissue tumors located outside the bone, while ultrasound and computed tomography (CT) scan are considered as alternative modalities.9\n\nAs for the subcutaneous hydatid cysts, the imaging technique that is mostly preferred is the ultrasonography. In this regard, it is worth noting that according to the literature review carried out by Kayaalp, ultrasonography, especially conducted by seasoned radiologists, enables the clear capture of such images and gives an accurate diagnosis to the patients. Cyst proximity to other organs can be evaluated utilizing CT scan and MRI.6\n\nThe therapy of choice for the subcutaneous hydatid cysts usually consists of medical treatment and surgery.\n\nWhile considering the treatment of such cysts, radical surgical resection of the cyst is indicated, however significant precautions are taken to avoid rupturing the cyst or disseminating the parasite within the surrounding soft tissues.8 This is usually done by placing the operating field under protection with hypertonic saline soaked packs. Considering the dimension of subcutaneous hydatid cysts, a considerable amount of skin can be lost during the surgical excision often requiring skin flaps.5\n\nHowever still, in the case of our patient, it was possible to perform primary closure even though the cyst was large.\n\nMost patients are prescribed albendazole as an adjunctive therapy for helminthic infestations that aims at decreasing the number of live cysts present as well as the chances of new infestations occurring.6\n\nThere were few complications after the operative removal of subcutaneous hydatid cysts and the chances of recurrence after complete surgical resection were very low.10 However, regular visits are important to monitor for any emergence of new growths.\n\nIn the context of the detection of a subcutaneous hydatid cyst, one should also look for the presence of other such cystic lesions in the body in the most efficient way.6\n\n\nConclusion\n\nPrimary subcutaneous hydatid cysts may be present in layers or tissue masses that may resemble soft tissue tumors; however, this is more dominant in areas where this disease is prevalent. Other visceral involvement should be looked for very carefully. The only way to avoid recurrence is to resect the lesion completely without any rupture.\n\n\nConsent\n\nWritten informed consent for publication of their clinical details and/or clinical images was obtained from the patient.\n\n\nAuthor contributions\n\nAymen Fekih: Project Administration, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing\n\nJacem Saadana: Methodology, Project Administration, Resources, Supervision, Validation, Visualization\n\nFiras Chaouch: Conceptualization, Supervision, Validation, Visualization\n\nFiras Boughattas: Conceptualization, Visualization\n\nIkram Haddada: Investigation, Resources, Validation, Visualization",
"appendix": "Data availability\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\n\nReferences\n\nSalih AM, Kakamad FH, Salih RQ, et al.: Hydatid cyst of the thigh: A case report with literature review. Int. J. Surg. Case Rep. 2018; 51: 8–10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAcu L, Acu B, Acu R, et al.: Hydatid cyst presented as a subcutaneous thigh mass. J. Ultrasound. 2016 Apr 8; 20(4): 321–324. PubMed Abstract | Publisher Full Text\n\nSalamone G, Licari L, Randisi B, et al.: Uncommon localizations of hydatid cyst. Review of the literature. G. Chir. 2016 Jul-Aug; 37(4): 180–185. PubMed Abstract | Publisher Full Text\n\nLemrhari B, Baha H, Azzouzi S, et al.: Isolated subcutaneous hydatid cyst: about a case and review of the literature. Pan Afr. Med. J. 2016 Jul 12; 24: 212. PubMed Abstract | Publisher Full Text\n\nÖzdemir M, Kavak RP, Kavak N, et al.: Primary gluteal subcutaneous hydatid cyst. IDCases. 2020 Feb 11; 19: e00719. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKayaalp C, Dirican A, Aydin C: Primary subcutaneous hydatid cysts: a review of 22 cases. Int. J. Surg. 2011; 9(2): 117–121. PubMed Abstract | Publisher Full Text\n\nGabriel Rodrigues G, Prabhu R: Primary Subcutaneous Hydatid Cyst of the Thigh: An Unusual Site With a Diagnostic Dilemma. J. Cutan. Med. Surg. 2016 May; 20(3): 266–268. PubMed Abstract | Publisher Full Text\n\nArkun R, Mete BD: Musculoskeletal hydatid disease. Semin. Musculoskelet. Radiol. 2011; 15(5): 527–540. Publisher Full Text\n\nBerquist TH, Dalinka MK, Alazraki N, et al.: Soft tissue masses. American College of radiology. ACR Appropriateness Criteria. Radiology. 2000; 215(Suppl): 255–259.\n\nVecchio R, Marchese S, Ferla F, et al.: Solitary subcutaneous hydatid cyst: review of the literature and report of a new case in the deltoid region. Parasitol. Int. 2013 Dec; 62(6): 487–493. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "340747",
"date": "10 Dec 2024",
"name": "Binod Paudel",
"expertise": [
"Reviewer Expertise Radio-medicine"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nIt feels interesting while going through this case report of subcutaneous hydatid cyst. Background , Case history, Examination findings and discussion section are clearly explained. Image section are congruent with the text section and also, references are fine. I feel confident that this case report will help in teaching learning process.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
},
{
"id": "353492",
"date": "30 Dec 2024",
"name": "Alin Mihetiu",
"expertise": [
"Reviewer Expertise General Surgery",
"Hepatobiliary and Pancreatic Surgery",
"Laparoscopic Surgery",
"Oncological Surgery"
],
"suggestion": "Approved",
"report": "Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThis article provides a well-structured presentation of this rare location of hydatid disease. The introduction makes a brief overview of the hydatid disease and its unusual locations, but it could also review other locations than those presented (pancreas, spleen, eyes, etc.). The case report part is well organized with good information and a smooth thread of presentation both in terms of the diagnostic stages and those of operative technique and postoperative evolution. The discussion chapter is well structured and succinctly touches on all the elements that build the approach to such a case.\n\nIs the background of the case’s history and progression described in sufficient detail? Yes\n\nAre enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes\n\nIs sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes\n\nIs the case presented with sufficient detail to be useful for other practitioners? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1259
|
https://f1000research.com/articles/13-518/v1
|
20 May 24
|
{
"type": "Research Article",
"title": "The development of a roadmap for Health Technology Assessment implementation in Moldova",
"authors": [
"Gavin Surgey",
"Ghenadie Curocichin",
"Maria Garabajiu",
"Tanja Novakovic",
"Adrian Pana",
"Wija Oortwijn",
"Ghenadie Curocichin",
"Maria Garabajiu",
"Tanja Novakovic",
"Adrian Pana",
"Wija Oortwijn"
],
"abstract": "Abstract*\nBackground Moldova strives for universal health coverage (UHC) and considers health technology assessment (HTA) an important policy instrument to inform the choice of services that should be covered to progressively realize UHC. It plays a key role in determining which technologies are coved, considering various dimensions often including cost-effectiveness, budget impact, and feasibility. This paper reports on work undertaken to develop a roadmap for HTA implementation, using evidence-informed deliberative processes (EDPs) as the guiding framework.\n\nMethods Between 2020 and 2022, we undertook several activities that informed the roadmap. We conducted a needs assessment and an assessment of European HTA best practices using a combination of desk research, interviews and surveys. We then conducted a document review of six selected HTA systems, complimented by expert interviews from three neighbouring countries.\n\nResults The roadmap provided a suggested HTA process, which included instructions on how to execute the different steps of the EDP framework to enhance the legitimacy of HTA-informed decision-making. The roadmap encompasses several aspects such as how to organize stakeholder involvement, how to identify and operationalize decision criteria, and how to make the decision process transparent. Guidance was given to the country on establishing a legal framework for HTA; a communication strategy; strengthening capacity and leveraging HTA expertise. The country was also given tailored advice on the positioning of the HTA-agency, first as an entity within the Ministry of Health or the National Agency of Public Health but with the long-term vision for it to be independent of any state institution.\n\nConclusions Despite several challenges, including a partial disruption because of the Covid-19 pandemic, the development of the roadmap for HTA implementation was completed and agreed upon by the Ministry of Health in Moldova. This work has helped motivate and support the country in HTA institutionalization.",
"keywords": [
"HTA",
"Health Technology Assessment",
"UHC",
"Priority-setting",
"Roadmap",
"Moldova",
"EDPs",
"Evidence-informed deliberative processes"
],
"content": "Introduction\n\nLike many countries worldwide that aim to achieve universal health coverage, Moldova views health technology assessment (HTA) as a significant policy tool as it plays a key role in determining which technologies are coved, considering various dimensions often including cost-effectiveness, budget impact, and feasibility.\n\nHTA is widely used internationally to inform resource allocation decisions. It is defined as “a multidisciplinary process that uses explicit methods to determine the value of a health technology at different points in its lifecycle. The purpose is to inform decision-making to promote an equitable, efficient, and high-quality health system.”1\n\nWhile HTA is still in its infancy in Moldova, the country has been supported by partners for the past years to improve their capacity for HTA. This paper reports on the process used to develop a roadmap for HTA implementation and activities with the overall objective to establish the most suitable HTA system in Moldova. The activities executed between October 2020 and June 2022 were funded by the World Bank and supported by the Ministry of Health (MOH) and the National Health Insurance Company (CNAM) in Moldova.\n\nWe employ evidence-informed deliberative processes (EDPs) as the guiding framework2 as well as experience with frameworks tested in other countries. The practical guidance on EDPs was developed by Radboudumc3 and provides recommendations of how to implement each step of the decision-making process of benefits package design. The guide takes the current decision-making context in a country as the starting point, offering practical support depending on the country’s level of HTA development.\n\nMoldova is one of the lowest income countries in Europe, with a Gross National Income (GNI) per capita of $4,570 in 2020. The country heavily relies on the agricultural sector, and its GDP per capita is estimated to be $5,231 in current US dollars.4 The constrained economic situation in Moldova can lead health system challenges such as funding shortages, limitations in service provision and increased out–of–pocket payments for users.\n\nIn 2019, the portion of GDP allocated to healthcare spending was 3.8%, which fell below the average of 6% for the European Union (EU) and 5% for South-Eastern Europe (SEE). However, it exceeded the average of 2.7% for lower-middle-income countries (LMIC) within the WHO European Region.5 Public spending on health as a share of GDP increased to 4.8% in 2020 likely due to an increase in spending related to Covid-19. The annual GDP change for the Republic of Moldova was –7% between 2019 and 2020 (World Bank, 2022).6\n\nA significant number of people in the Republic of Moldova still lack access to affordable and high-quality essential healthcare services. To address this issue, the Moldovan government established a national purchasing agency (CNAM), which aimed to pool individual and state contributions. The objective was to create a strong foundation for gradually expanding the coverage of healthcare services and medications provided by CNAM to a larger portion of the population.7\n\nWhile this initiative has resulted in improved accessibility to healthcare services and a decrease in unmet needs, Moldova still experiences a higher incidence of catastrophic health expenditure compared to other countries in the WHO European Region. This is primarily due to persistent gaps in healthcare coverage.8 Although CNAM has been progressively increasing the number of medicines it covers, there are still essential medications that are not included, and outpatient medicine coverage remains limited.\n\nThe entitlement to publicly funded benefits under mandatory health insurance in Moldova is defined by the 1998 Law on mandatory health insurance (No.1585-XIII). The purpose of mandatory health insurance is to guarantee equal access to healthcare for all residents, who are obliged to be covered by CNAM.\n\n\nMethods\n\nThe framework that we used for developing an HTA roadmap concerned evidence-informed deliberative processes (EDPs), combined with frameworks tested in other countries.9 EDPs3 can be used to guide countries to improve their decision-making processes,10,11 and have been implemented successfully in a range of low, middle and high-income countries.12,13 The core concept of EDPs centers around legitimacy and is broken down into four key elements, with stakeholder involvement and transparency being of utmost importance. The EDP framework offers a pragmatic and systematic approach tool for priority setting in health. Its primary objective is to enhance the credibility of benefit package choices and associated results, such as population health and financial risk mitigation. The activities encompassed in this project includes a needs assessment, an assessment of best practices and the development of the roadmap.\n\nWe conducted a needs assessment to understand the decision-making context in which HTA could be used, stakeholders and their (potential) roles and, the capacity and skills for HTA within the country. The needs assessment consisted of three building blocks namely: a situational analysis, stakeholder analysis and a capacity and skills assessment through which we conducted interviews and surveys. To conclude the phase of the needs assessment, a virtual workshop was held with participants to show preliminary results from the needs analysis and to use the opportunity to conduct some capacity strengthening around HTA. Data collection instruments were developed and approved both by the Moldova National Ethical Committee (Date 22.12.2020 Nr. 1023) and Nicolae Testemitsanu SUMPh Committee for Research Ethics (Date 28.12.2020 Nr. 2). Data was collected between April– May 2021.\n\nA list of potential participants was compiled through an online search and our knowledge of the situation in the country. The online search consisted of reviewing the MOH website, National Health Insurance (NHIC) website and a general Google search. We classified all stakeholders according to the 7Ps (policymakers, payers, product makers, principal investigators, patients and the public, providers, and purchasers) to ensure that we had a representative sample of each stakeholder.14 Subsequently, our list of potential respondents was reviewed and revised by the World Bank and the MOH and an official letter of request to participate in the study was provided.\n\nThe situational analysis aimed to establish the feasibility of EDP application in Moldova. We conducted a desktop review using standard health indicators and the list of services currently included in the MHI to match supply and demand. This was to help understand data availability relevant to HTA development, priority setting, and evidence-informed decision making; to help understand the current policy landscape that could support the institutionalisation of HTA, and to describe relevant stakeholders and the political landscape in Moldova.\n\nIn parallel, we collected views through semi-structured interviews with identified stakeholders to understand their knowledge of, position regarding, and interest in HTA.\n\nThe interview protocol15 was based on Oortwijn et al.16 which consisted of elements that reflect each step of the EDP framework and the contextual factors for HTA development.\n\nThe stakeholder analysis aimed to identify and analyse potential stakeholder roles. We adapted and applied a stakeholder mapping tool15 developed by Vlad.17\n\nThe different perspectives and roles of various stakeholders would help understand who might influence and shape governance structures and legislative measures to support HTA institutionalisation and how far evidence-building tools such as HTA would be taken into account in decision-making.\n\nThrough a survey,15 we assessed the available capacity and skills for HTA in Moldova of both ‘do-ers’ and users of HTA, although many of the respondents completed the survey in the presence of researchers. The survey was based on an existing set of tools tested out in other country assessments,18 complemented with literature.19\n\nTo draw lessons in implementing HTA in Moldova we assessed best practices in HTA which involved a mapping of HTA systems in Europe. For this purpose, we undertook literature reviews and conducted interviews with key stakeholders.\n\nWe first conducted a review of ‘comparative analyses’ from published literature in the last 5 years and then a focused analysis of six countries’ HTA systems.\n\nFor the focused analysis we selected three early adopters (or mature) and three ‘recent’ (or nascent) adopter countries based on our review and experience. These were England, Scotland and Germany (early adopter countries) and Romania, Poland and Ukraine (recent adopters).20\n\nThe focused analysis examined each country’s HTA system according to each step of the EDP framework: A. installing an advisory committee; B. selecting decision criteria; C. selection of health technologies for HTA; D1. scoping; D2. assessment; D3. appraisal; E. communication and appeal; and F. monitoring and evaluation.3 For this, we reviewed key documents and websites of HTA bodies to assess practices both in terms of HTA institutional design and the HTA process.\n\nFor a selection of countries that could serve as an inspiration for Moldova, we conducted in-depth, semi-structured interviews with key experts and policymakers who were knowledgeable about their countries’ HTA system and to consider the transferability of the lessons learned to Moldova. We identified 3-5 stakeholders per country, via our networks, and invited them for a telephone interview.\n\nThe interview focused on the establishment of HTA in the respective country, and the steps of EDPs where we validated and/or updated the findings from the literature review of HTA systems.\n\nSemi-structured in-depth interviews were conducted with senior Moldova representatives including three from the Ministry of Health, and four from the National Agency for Public Health to learn more about the Moldavian health system and the vision that for HTA in the country.\n\nA workshop with stakeholders was held to validate the lessons to be drawn from the review and the neighbouring countries. The workshop also aimed to discuss key elements from other countries that would work in Moldova and where more work would be needed, both in terms of HTA institutionalisation and HTA processes.\n\nThe workshop also aimed to validate the recommendations developed and help create buy-in and legitimacy for the implementation plan to be developed.\n\nUsing a synthesis of findings from the needs assessment, assessment of best practices, and further discussions with key stakeholders from Moldova, a roadmap for HTA in Moldova was developed.\n\n\nResults\n\nThere were 61 participants initially identified, and 55 were agreed to be contacted by e-mail. Potential participants who did not respond to the e-mail were sent a reminder 2 weeks after the initial invitation. On the second follow-up, six participants explicitly abstained from participation – due to several reasons including changing positions and a feeling of not being entitled to make decisions as their positions were solely technical in nature. A further six potential participants did not reply to the email nor phone calls. Respondents who accepted the invitation by e-mail were contacted by phone for scheduling the interview or agreed to complete the survey independently. An additional 3 technology producers were contacted through our networks as we had difficulty securing participants from this stakeholder category. Of these, 2 were successfully interviewed.\n\nThe number of respondents for each (7P) stakeholder category who participated are shown in Table 1.\n\nConcerning the interviews with selected country key experts, we aimed to get 3-5 respondents (in Poland, Romania and Ukraine). However, it was challenging to get a timely response from more than 5 so we decided to interview at least 3 experts in each country, representing different stakeholder groups (Table 4). We did not reach out to additional stakeholders once we had a minimum of 3 stakeholders per country.\n\nVery few respondents felt that they were very familiar (33%) with HTA, although some (58%) indicated they had partial familiarity. When questioning respondents regarding the potential involvement of their organization in HTA, 17 respondents (71%) indicated that they or their organizations would have involvement in HTA indicating that this was the correct target audience for the survey.\n\nRespondents indicated that Moldova is in the nascent phase of applying (elements of) EDPs for legitimate health benefits package design. There were, however, several elements that were shown to already be in place in Moldova which is in line with the HTA process including decision-making (advisory) committees with a level of legitimacy through government (legal) orders. The advisory committee for medicines called the “Council for Compensated Medicines” makes decisions on which medicines to include in their essential medicines list.\n\nFor all the steps and elements stipulated in the EDP framework, we probed whether there was a need for further guidance. Unsurprisingly, the majority of respondents felt that guidance was needed for all steps.\n\nWe received complete responses from a total of 23 individuals who were either interviewed or completed a survey form before the interview which we followed up on afterwards.\n\nThe stakeholder analysis helped identify relevant stakeholders and their role or level of importance in priority setting in Moldova. This is shown in Table 2.\n\nWe found that respondents reported several stakeholders involved in priority setting and that there is seemingly a collaborative environment between stakeholders.\n\nIn trying to understand the role of politicians/appointed decision-makers in defining the benefits package, respondents stated that their main role is around decision-making and approval of decisions. They noted that they have the responsibility for applying changes to the benefits packages such as updating with new medicines. There were no stated political tensions or disagreements. Civil servants and non-health professional decision-makers had similar roles, but there their specific role in the process was not clear. When it came to an understanding of the process of defining the benefits package it was reported that the MOH was responsible for coordinating the procedure with CNAM (the health insurer) and that there were appointed committees responsible for this, but the overall procedure was not clear to respondents.\n\nThe Center for Centralized Public Procurement in Healthcare (CAPCS) was stated as having responsibility for the procurement of medical products. The Agency for Medicines and Medical Devices (AMDM) was noted as having responsibility for negotiating prices, although there was no clear consensus among respondents. Respondents mentioned several stakeholders as having responsibility for pricing.\n\nWhen it comes to decision-making, respondents felt that Patients or carer groups and the public were given a voice either partially (33%) or fully (27%). However, voting on decisions is restricted to only a few key policy-makers and this means that there is mostly consultation of stakeholders and very little participative decision-making.\n\nThe majority of respondents to the survey had expertise in the field of public health and management. There was an equal split between those who classified themselves as decision-makers (users) or researchers (producers/do-ers).\n\nWe found that half of the respondents (50%) were part of, or had previously belonged to a government advisory committee of some sort and thus showed an average or above-average level of competence in related leadership or management skills. There was a good percentage of respondents (81%) who had experience with, and specific skills in conducting academic research and writing publications. This could partly be explained by the fact that there was a significant proportion of respondents (21%) who were employed by a university/research organisation.\n\nRespondents rated their technical skills related to HTA as being moderate with more than half showing that they had specific experience in the majority of categories. Some respondents (31%) stated that they had read HTA reports from other countries, although there was a lower amount (15%) who stated that they had used the results from other countries.\n\nHowever, when it came to specific technical skills (such as economic evaluations) the majority indicated a low level of confidence. Few showed confidence in conducting appraisals which is a key element of the HTA process where the results of the assessment need to be interpreted from a broader perspective and where recommendations are developed to inform decision-making.\n\nResults relating to the capacity and skills assessment can be found in Table 3.\n\nTwenty-five individuals attended the workshop primarily from the MOH and CNAM. Preliminary results from the needs assessment were shown and discussed. The role of stakeholders was highlighted and there was discussion about how to further engage other stakeholders to actively participate in the process. Participants agreed that the level of understanding around HTA was too weak which might explain the current lower level of engagement around HTA.\n\nCapacity strengthening was also undertaken to further sensitize on UHC, and HTA concepts and methods. EDPs were presented as a practical approach to implementing HTA in Moldova, and how these processes could be used to promote legitimate decision-making on the path to UHC.\n\nA review of ‘comparative analyses’ from published literature in the last 5 years shows that the majority (29 out of 31 countries, 94%) of countries (where information was available) use some elements of HTA to support decision-making about the use of pharmaceuticals. HTA activity was found to be lower for non-pharmaceutical health technologies with 71% of countries (22 out of 31 countries) using HTA to support decision-making.\n\nThe comparison of the six selected countries, early adopters (England, Scotland and Germany) and recent adopters (Poland, Romania and Ukraine) show that:\n\n• In early adopter countries, stakeholders are involved in nearly all HTA processes which is not the case in recent adopter countries. It appears that there is no stakeholder engagement in most steps;\n\n• Early adopters (Germany and England) conduct explicit monitoring and evaluation of decisions, while recent adopters seem not to monitor or evaluate the results of HTA decisions;\n\n• Training of stakeholders exists in early adopter countries and Poland, but not in Ukraine and Romania;\n\n• Assessment and appraisal phases are the most developed processes across all countries, with methodological HTA guidelines in place in England, Poland and Ukraine. The Polish appraisal process seems to have the highest level of transparency compared to the other two recent adopters (Romania and Ukraine).\n\nDiscussions with key experts gave insight as to some of the reasons the country had introduced HTA and some conducive factors. How HTA was set up and other recommendations for newly establishing HTA in a country.\n\nThe main reasons respondents gave for introducing HTA were economic concerns such as budget around spending on health and the need for cost-containment. Some conducive factors to introducing HTA was political will supported by new legislation to enforce HTA. Other key success factors that respondents noted included building support for various stages in the establishment of HTA and having a close collaboration with all stakeholders including industry and patients throughout the process.\n\nExperts also gave some recommendations to Moldovan policymakers on establishing HTA. These included ensuring the involvement of multiple stakeholders and building support for the various stages of HTA and establishing a solid methodology and processes containing all the steps for HTA. Experts also advised on the importance of creating an HTA assessment body independent of state authorities to make decisions regarding reimbursement and building the right legislation around this. It was also recommended to continuously invest and build the institutional capacity of those involved in HTA in the country.\n\nA final workshop was held with approximately 25 individuals primarily from the MOH and CNAM. Experiences and best practices were shared with presenters who lead HTA activities in Poland and Ukraine. Presentations and discussions were held on the current situation of Moldova (issues and challenges) and how the country can move towards the establishment of an HTA system.\n\nDuring the workshop it was discussed where the HTA unit should be based - it was agreed that for now it should start with either the MOH or the National Agency of Public Health but the long-term vision would be for it to be independent of any state institutions. The main purpose agreed upon during the workshop was for the HTA unit to focus on developing the benefits package and keeping the Essential Medicines List up to date.\n\nThe development of the roadmap took into consideration all the findings and other discussions that were held with Moldavian stakeholders instrumental in the design of HTA. The roadmap covered the HTA institutional design in terms of the responsibilities of participating organizations in implementing HTA evidence into policy. The roadmap also gave details of a proposed HTA process including guidance on how to implement the steps of the EDP framework. This included providing suggestions on how to effectively organize stakeholder involvement, how to potentially identify and operationalize decision criteria, and how to best make the decision process transparent. Specific guidance was given to the country on establishing a legal framework for HTA; a communication strategy; strengthening capacity and leveraging HTA expertise. Recommendations given were in line with the 2020 WHO report “Principles of health benefit packages”,21 and the “roadmap for systematic priority setting and HTA” by Castro, Kumar, Suharlim et al.22\n\n\nDiscussion\n\nThis paper outlines the components that can support the successful development of a roadmap for HTA implementation in Moldova. HTA leads to better informed benefit package and improved access to essential services which is critical for the achievement of UHC.23,24 Through this research, we find that there is a high demand and appetite by all stakeholders for HTA in the country. It showed that there is a strong political will, but this is driven by very few within the government making the success of Moldova very dependent on a few individuals who have already stretched agendas. There are a few stakeholders that have received some training on HTA however, there is still a lot more sensitization needed across all stakeholder groups. There are limited resources including human and financial resources but also a limited amount of country-specific data. However, the country has some decision-making systems and processes that can be harnessed for HTA. We believe that any additional guidance on existing processes will only strengthen the processes for Moldova.\n\nCurrently, there are a handful of activities taking place to establish HTA in the country which were known by respondents including demonstration projects and some training courses in the field of HTA. However, given the number of stakeholders (individuals and departments) who were reported to have kickstarted the establishment of HTA, we might expect to see more activities currently taking place.\n\nThe surveys conducted did have some shortfalls, for example when measuring skills, we did not provide a definition of terms meaning respondents could have interpreted these differently. Results are therefore prone to measurement bias. We saw this when asking knowledge questions, i.e. asking a respondent to rate their knowledge on a topic and then asking them a verification question on that topic. We found that they did not always rate their knowledge correctly. As such, there is a need for creating awareness, training and education in HTA. Stronger technical skills are needed in using different types of evidence (reviewing evidence) and interpreting economic evaluations.\n\nInvolving multiple stakeholders is expected to enhance the credibility of Moldova's decision-making process.3 Two successful workshops were conducted with stakeholders to ensure alignment of objectives and consensus on advancing Health Technology Assessment (HTA) in the country. In these sessions, stakeholders reached a mutual understanding regarding the rationale, goals, and scope of HTA initiatives. Institutionalizing HTA and enhancing the legitimacy of this process will reinforce the overall credibility of decision-making and foster greater transparency, given the comprehensive involvement and informed status of numerous stakeholders.\n\nThe overall project and development of the roadmap did face a challenge in that almost all of the work was developed remotely given the disruption due to COVID-19. Implementation of the roadmap will likely also experience delays due to pressing issues related to COVID-19 and the current situation in Ukraine. Moldova has, however, started to take some of these recommendations forward in developing capacity-strengthening options with local universities. Building skills in this area will help drive the process of institutionalization of HTA in Moldova.\n\nAn important contribution of this paper is to demonstrate how countries can institutionalise HTA for the achievement of UHC. Critical to the success is the continuous political will and determination of the government25 of coupled with comprehensive stakeholder engagement.26,27 From here, HTA should be linked to policy decision-making supported by the HTA legislation with a permanently financed core team focused on HTA.28 At the same time, developing formal HTA training capacity so that over time, skills and expertise are built. This needs to be accompanied by continuous awareness raising among users of HTA. International collaboration with other countries that are further in the HTA process as well as international networks such as HTAi and INAHTA can support Moldova in the implementation of the roadmap.\n\nEthical approval for this study was obtained from the National Committee for Ethical Expertise of Clinical Trial (NCEECT/1023/22.12.2020) on 22.12.2020 and Nicolae Testemitanu State University of Medicine on and Pharmacy (94) on 21.12.2020. All participants gave either verbal or written informed consent depending on the nature of the survey. Verbal informed consent was used when participants were supported in completing a survey form, or when an survey form was completed on their behalf.",
"appendix": "Data availability\n\nOSF: Roadmap for HTA implementation in Moldova [dataset] OSF: DOI 10.17605/OSF.IO/NPKBF\n\nFile ‘Moldova HTA Roadmap data’ contains individual underlying data for each 3 surveys\n\nFile ‘1. Instrument - Situational Analysis.docx’ contains situational analysis instrument\n\nFile ‘2. Instrument - Stakeholder Analysis.docx’ contains stakeholder analysis instrument\n\nFile ‘3. Instrument - Capacity Skills Assessment.docx’ contains capacity skills assessment instrument\n\nFile ‘4. Review of early and recent adopter countries against EDP steps.docx’ contains individual country level results\n\nAll data underlying the results are available as part of the article and no additional source data are required.\n\nData are available under the terms of the CC0 licence CC0 1.0 Universal\n\n\nAcknowledgements\n\nWe would like to thank to officials in the Republic of Moldova from the Ministry of Health and CNAM. We are also sincerely grateful to Rob Baltussen who helped shape the project in the development phase and supported the workshops. Finally, we appreciate the continuous support of Volkan Cetinkaya and Ilie Volovei and the rest of the World Bank Project Team.\n\n\nReferences\n\nO’Rourke B, Oortwijn W, Schuller T: The new definition of health technology assessment: A milestone in international collaboration. Int. J. Technol. Assess. Health Care. 2020 Jun; 36(3): 187–190. PubMed Abstract | Publisher Full Text\n\nOortwijn W, Jansen M, Baltussen R: Evidence-informed deliberative processes for health benefit package design–part II: a practical guide. Int. J. Health Policy Manag. 2022 Oct; 11(10): 2327. Publisher Full Text\n\nOortwijn W, Jansen M, Baltussen R: Evidence-informed deliberative processes. A practical guide for HTA bodies for legitimate benefit package design. Version 2.0. Nijmegen: Radboud University Medical Center; 2021.\n\nWorld Bank. Overview - Moldova [Internet]. [cited 2023.03.01]. : Reference Source\n\nWorld Health Organization: Health systems in action: Republic of Moldova: 2022 edition.2022.\n\nWorld Bank: World Development Indicators. Washington, DC: World Bank; 2022.\n\nGaram I, Zadnipru M, Doronin V, et al.: Can people afford to pay for health care? New evidence on financial protection in the Republic of Moldova.2020.\n\nCylus J, Thomson S, Evetovits T: Catastrophic health spending in Europe: equity and policy implications of different calculation methods. Bull. World Health Organ. 2018; 96(9): 599–609. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJeffery M, Chi YL, Stewart M: iDSI Health Technology Assessment Toolkit [version 1; not peer reviewed]. F1000Res. 7(1545). Publisher Full Text\n\nBaltussen R: Value assessment frameworks for HTA agencies: The organisation of evidence-informed deliberative processes. Value Health. 2017; 20: 256–260. PubMed Abstract | Publisher Full Text\n\nOortwijn W, Jansen M, Baltussen R: Use of evidence-informed deliberative processes by health technology assessment agencies around the globe. Int. J. Health Policy Manag. 2020; 9(1): 27–33. PubMed Abstract | Publisher Full Text\n\nNouhi M, Baltussen R, Razavi S, et al.: The use of evidence-informed deliberative processes for health insurance benefit package revision in Iran. Int. J. Health Policy Manag. 2022; 11(11): 2719–2726. PubMed Abstract | Publisher Full Text\n\nOortwijn W, Surgey G, Novakovic T, et al.: The Use of Evidence-Informed Deliberative Processes for Health Benefit Package Design in Kazakhstan. Int. J. Environ. Res. Public Health. 2022 Sep 10; 19(18): 11412. PubMed Abstract | Publisher Full Text | Free Full Text\n\nConcannon T, Meissner P, Grunbaum J: A new taxonomy for stakeholder engagement in patient-centered outcomes research. J. Gen. Intern. Med. 2012; 27(8): 985–991. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSurgey G, Oortwijn W, Curocichin G, et al.: Roadmap for HTA implementation in Moldova. [dataset]. 2024 [cited 2024 Mar 21]. Reference Source\n\nOortwijn W, van Oosterhout S , Kapiriri L: Application of evidence-informed deliberative processes in health technology assessment in low-and middle-income countries. Int. J. Technol. Assess. Health Care. 2020; 36(4): 440–444. PubMed Abstract | Publisher Full Text\n\nVlad I: Stakeholder checklist for priority-setting in low and middle-income countries [version 1; not peer reviewed]. F1000Res. 2018; 7: 1718.\n\nSurgey G, Mori AT, Baltussen R: Health Technology Assessment in Tanzania: Capacity and Experience of HTA Committee Members. J. Glob. Health Econ. Policy. 2022; 2: e2022004. Publisher Full Text\n\nPichler F: Defining Capacity Building in the Context of HTA: A Proposal by the HTAi Scientific Development and Capacity Building Committee. Int. J. Technol. Assess. Health Care. 2019; 35(5): 362–366. PubMed Abstract | Publisher Full Text\n\nBeletsi A, Koutrafouri V, Karampli E, et al.: Comparing use of health technology assessment in pharmaceutical policy among earlier and more recent adopters in the European Union. Value Health Reg Issues. 2018; 16: 81–91. PubMed Abstract | Publisher Full Text\n\nWorld Health Organization: Principles of Health Benefit Packages. Geneva: World Health Organization; 2021.\n\nCastro HE, Kumar R, Suharlim C: A Roadmap for Systematic Priority Setting and Health Technology Assessment (HTA). Arlington, VA: USAID/MSH; 2020.\n\nBertram M, Dhaene G, Tan-Torres ET: Institutionalizing Health Technology Assessment Mechanisms: A How-to Guide. Bertram M, Dhaene G, Tan-Torres Edejer T, editors. Geneva: World Health Organization; 2021.\n\nNorheim O, Watkins D: The Role of HTA for Essential Health Benefit Package Design in Low or Middle-Income Countries. Health Syst. Reform. 2023; 9(3): 2273051. Publisher Full Text\n\nMueller D: Addressing the challenges of implementing a Health Technology Assessment Policy framework in South Africa. Int. J. Technol. Assess. Health Care. 2020 Aug; 36(4): 453–458. PubMed Abstract | Publisher Full Text\n\nMitton C, Smith N, Peacock S, et al.: Public participation in health care priority setting: a scoping review. Health Policy. 2009 Aug 1; 91(3): 219–228. PubMed Abstract | Publisher Full Text\n\nKapiriri L, Baltussen R, Oortwijn W: Implementing evidence-informed deliberative processes in health technology assessment: a low income country perspective. Int. J. Technol. Assess. Health Care. 2020; 36(1): 29–33. PubMed Abstract | Publisher Full Text\n\nSurgey G, Chalkidou K, Reuben W, et al.: Introducing health technology assessment in Tanzania. Int. J. Technol. Assess. Health Care. 2020; 36(2): 80–86. PubMed Abstract | Publisher Full Text"
}
|
[
{
"id": "288862",
"date": "14 Jun 2024",
"name": "Christian Suharlim",
"expertise": [
"Reviewer Expertise Health Technology Assessment in LMICs",
"economic evaluation"
],
"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. The authors did an excellent job in describing, in detail, the activities conducted in order to assess the needs, propose improvements, and develop the HTA Roadmap. I suggest a few revisions below:\nAuthors described in [Results-Stakeholder analysis] \"However, voting on decisions is restricted to only a few key policy-makers and this means that there is mostly consultation of stakeholders and very little participative decision-making.\" I would have liked to see a deeper dive into this aspect in the Discussion section, e.g., Does this align with what researchers would expect ex-ante for a country with Moldova's history and government? Does the comparative analysis shed insight on how Moldova compares in this regard to other post-Soviet states? How is this improved in the new roadmap? Authors put quotation marks around the term comparative analyses. I wonder why this is the case. I would have liked to have more detail on how the 5-year published literature desk review was conducted under [methods] and a table of the findings under [results] and [Supplementary data] In the introduction, the Authors specifically mention how Moldova is lower on the development level in Europe- as proxied by GNI/capita. However, the six focused countries are mostly high-income countries with vastly different development levels. Under [Discussion], I would like to see how authors synthesize the impact of the development level difference between these countries and Moldova and how it may impact the generalizability and applicability of a country with a much lower development level. In particular, it would be excellent if authors could comment on human resource capacity, e.g., human flight and brain drain, and how that may impact a country with such issues to meet the unfair expectations of the gold standards set by early adopters. Under [Results-development of a roadmap] \"Experiences and best practices were shared with presenters\" - or \"by presenters\"? Under [Discussion], the authors state, \"It showed that there is a strong political will, but this is driven by very few within the government, making the success of Moldova very dependent on a few individuals who have already stretched agendas.\" I would have expected this to be the case in most countries with lower development levels.Does this align with the Authors' desk review / comparative analyses? If this is indeed the typical lay of the land in LMICs, is there a precedent to more positive wording (e.g., 'local champions'?) The authors state their limitations in the survey. I would have liked to see if authors could synthesize their thinking on the current limitations with the desk review, interviews, sample size and selection, and interpretation of data. The authors made a point about improving stakeholder involvement. However, I would have liked to see the intensity and extent of these 'new stakeholders' contributions. What (if any) decisions would have been different had they not been a part of the contribution? Beyond the cited theory and paper, in Moldova, how would their involvement improve the legitimacy of decisions? Were there explicit buy-ins and endorsements by the new stakeholders' affiliated organizations? Lastly, this is a really well-done paper and process. The authors would benefit from more explicit statements that one of the strengths of this study is the multi-stage sequential mixed-method approach, which allowed them to assess needs methodically and offer solutions.\nCongratulations for the excellent work and a job well-done! Best regards, Chris Suharlim\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? No\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12608",
"date": "21 Oct 2024",
"name": "Gavin Surgey",
"role": "Author Response",
"response": "Thank you for the comments. We have responded to each of the comments in turn, and indicated where we have made additions to the paper. Thank you for the suggestions – we believe they have added to the overall paper. 1. Authors described in [Results-Stakeholder analysis] \"However, voting on decisions is restricted to only a few key policy-makers and this means that there is mostly consultation of stakeholders and very little participative decision-making.\" I would have liked to see a deeper dive into this aspect in the Discussion section, e.g., Does this align with what researchers would expect ex-ante for a country with Moldova's history and government? Does the comparative analysis shed insight on how Moldova compares in this regard to other post-Soviet states? How is this improved in the new roadmap? Ans: We have added additional information related to: Alignment with expectations for Moldova – a paragraph was added in the discussion section Comparison to other post-Soviet states Improvements in the new roadmap and how learning from both regional peers and more established HTA systems, the new roadmap aims to accelerate Moldova's progress in this area. 2. Authors put quotation marks around the term comparative analyses. I wonder why this is the case. I would have liked to have more detail on how the 5-year published literature desk review was conducted under [methods] and a table of the findings under [results] and [Supplementary data] Ans: We attempted to make this more clear by adding additional information in the paper including: We did not use the information to compare countries, but rather to give an overview of the HTA landscape in Europe. We did not include a table of findings for the comparative analysis as this mainly served as background information for selecting countries for the focused analysis – and this was not the aim of the analysis. The table of findings for the focused analysis are presented in supplementary data file: File ‘4. Review of early and recent adopter countries against EDP steps.docx’ contains individual country level results An additional supplementary file was added (#5) to give a listing of the of the resources we used to gather the findings. 3. In the introduction, the Authors specifically mention how Moldova is lower on the development level in Europe- as proxied by GNI/capita. However, the six focused countries are mostly high-income countries with vastly different development levels. Under [Discussion], I would like to see how authors synthesize the impact of the development level difference between these countries and Moldova and how it may impact the generalizability and applicability of a country with a much lower development level. In particular, it would be excellent if authors could comment on human resource capacity, e.g., human flight and brain drain, and how that may impact a country with such issues to meet the unfair expectations of the gold standards set by early adopters. The countries were selected to serve as inspiration. Ans: We added information: We will select 2-3 countries that could serve as an inspiration for HTA development in Moldova. In choosing these countries, we started to develop a selection tool that includes the following criteria: similar health system financing and organization of health services delivery, although the perspective used in HTA may differ (health system verses societal perspective), level of HTA development (intermediate/mature level, e.g. Croatia, Poland, Romania, Ukraine), level of EDP development or interested in EDP uptake (e.g. Kazakhstan, Ukraine). 4. Under [Results-development of a roadmap] \"Experiences and best practices were shared with presenters\" - or \"by presenters\"? Ans: Thanks for picking this up: “by presenters” is correct 5. Under [Discussion], the authors state, \"It showed that there is a strong political will, but this is driven by very few within the government, making the success of Moldova very dependent on a few individuals who have already stretched agendas.\" I would have expected this to be the case in most countries with lower development levels. Does this align with the Authors' desk review / comparative analyses? If this is indeed the typical lay of the land in LMICs, is there a precedent to more positive wording (e.g., 'local champions'?) Ans: The terms \"political will\" and \"local champions\" are related but distinct. A \"local champion\" usually refers to an individual, not necessarily in government, who drives forward a specific agenda. In contrast, \"political will\" refers to the collective determination of a group of individuals within the government to pursue a particular course of action. While a local champion may lead or inspire efforts, political will reflects a broader, shared commitment within the governing body. We have not made any changes to this 6. The authors state their limitations in the survey. I would have liked to see if authors could synthesize their thinking on the current limitations with the desk review, interviews, sample size and selection, and interpretation of data. Ans: Some additional details relating to the limitations were added to the discussion section relating to the desk review. We also added additional paragraph on the multi-stage approach. 7. The authors made a point about improving stakeholder involvement. However, I would have liked to see the intensity and extent of these 'new stakeholders' contributions. What (if any) decisions would have been different had they not been a part of the contribution? Beyond the cited theory and paper, in Moldova, how would their involvement improve the legitimacy of decisions? Were there explicit buy-ins and endorsements by the new stakeholders' affiliated organizations? Ans: We appreciate the suggestion to further analyze the impact of expanded stakeholder involvement. You raise good questions about the tangible effects of including new stakeholders. We did not assess how specific decisions differ. We can at this time only refer to theoretical arguments and examples of other countries where stakeholder involvement improves legitimacy of decisions as well as buy-ins and endorsements. However, we agree this could be more thoroughly analysed as a separate piece of future work. 8. Lastly, this is a really well-done paper and process. The authors would benefit from more explicit statements that one of the strengths of this study is the multi-stage sequential mixed-method approach, which allowed them to assess needs methodically and offer solutions. Ans: Thanks for this suggestion, it has been added to the paper. We appreciate these insightful comments which will help strengthen both this paper and our ongoing work supporting HTA development in Moldova and other countries. Are sufficient details of methods and analysis provided to allow replication by others? All the instruments and source data is available online. This is detailed in the “Data availability section”: OSF: Roadmap for HTA implementation in Moldova [dataset] OSF: DOI 10.17605/OSF.IO/NPKBF If applicable, is the statistical analysis and its interpretation appropriate? Partly Descriptive analysis techniques were used. These methods are detailed in the paper with the individual results in the source data. OSF: Roadmap for HTA implementation in Moldova [dataset] OSF: DOI 10.17605/OSF.IO/NPKBF Are all the source data underlying the results available to ensure full reproducibility? No All the instruments and source data is available online. This is detailed in the “Data availability section”: OSF: Roadmap for HTA implementation in Moldova [dataset] OSF: DOI 10.17605/OSF.IO/NPKBF Are the conclusions drawn adequately supported by the results? Yes"
}
]
},
{
"id": "288867",
"date": "25 Jun 2024",
"name": "Kanchan Mukherjee",
"expertise": [
"Reviewer Expertise HTA",
"Health Policy",
"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\nThis paper documents the process used for developing a road map for HTA implementation in Moldova. The methodology involved using the EDP framework, which has been applied before, and thus provides transparency with scope for replicability. The steps included needs assessment (situational analysis, stakeholder analysis, capacity assessment), which provided an internal contextual assessment of the HTA situation in Moldova. This was complemented by assessment of best practices, and neighboring countries key expert interviews, which provided the external contextual analysis. Overall, the above activities suggest a holistic approach to the situation, while acknowledging the contextual influence. Contextualisation of HTA is extremely important and has also been reported in literature in creating a road map for HTA in India, which is a low-middle-income country (like Moldova) (Mukherjee K et al, 2017) [Ref 1] The methodology followed is comprehensive and justifiable given the objective of this exercise. It also reflects a well thought out process which is systematic and specific, while acknowledging the limitations of such a process. The conclusions and discussion reflect the positive aspects (high demand by stakeholder) as well as the challenges (few policy champions for HTA, low HTA capacity). India also encountered a similar situation like Moldova, when the process of HTA was first conceived at the political level and continues to face similar challenges in its implementation. From my HTA experience in the Indian context, I am sharing a few learnings, which maybe useful for Moldova:\nPolitical institutionalization is extremely important, but the HTA body should be an autonomous entity to avoid political interference in the HTA process. Academic institutionalization of HTA through local universities is a sustainable model for capacity building in HTA. Hence, it may also be useful to consider academic institutionalization of HTA in local universities in the form of Masters/PhD programme or short term training programmes, in which policy makers/implementers, can also be nominated to be trained in the HTA process. This model has been implemented in India since 2010 and has resulted in a demand creation in this niche area as well as increased sensitization and awareness among policy makers about HTA (Mukherjee K, et al 2020) [Ref 2]. It may be useful to have small pilot HTA projects (‘mini-HTA’) at the initial stages to provide credibility, legitimacy and acceptance by various stakeholders. Hence, simple incremental steps in HTA based on existing resources and decision making mechanisms maybe useful before using HTA for complex issues. The HTA ecosystem should be an open system receptive to learnings (internal and external), adaptive and responsive to evolving challenges over time. Hence, it would be useful to have a follow up review to assess the extent of implementation of HTA in Moldova.\nTo conclude, I congratulate the team for their efforts in this exercise, which by itself would have resulted in sensitization of stakeholders and started the first step towards HTA implementation in Moldova.\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": []
}
] | 1
|
https://f1000research.com/articles/13-518
|
https://f1000research.com/articles/11-1192/v1
|
18 Oct 22
|
{
"type": "Research Article",
"title": "Conceptualizing university students’ food choices based on theory of planned behavior",
"authors": [
"Kshama Vishwakarma",
"Varalakshmi Chandra Sekaran",
"Vidya Patwardhan",
"Asha Kamath",
"Kshama Vishwakarma",
"Vidya Patwardhan",
"Asha Kamath"
],
"abstract": "Background: Several students use hostel facilities offered by their colleges and universities while pursuing higher education. A crucial change is witnessed in their food habits during their stay at the campus, which is vastly different from their home experience.\nMethod: The study employs the theory of planned behavior to conceptualize and understand food choices of university students, while following the qualitative research methodology and the phenomenological approach. The snowball sampling method is applied to select participants for the study. We selected twenty-six undergraduate and postgraduate students pursuing programs in technical and health science from a private university at Udupi with residence in the university campus for two to four years. Interviews with candidates were conducted online and audio-recorded with participants’ consent. Results: The transcribed interviews were coded and categorized to obtain themes, which were then conceptualized to develop the model based on theory of planned behavior. The duration of their stay in campus allowed students to gain a perspective on the food events and the food they consumed at university dining facility (UDF) guided by factors, such as taste, price, availability of time(during academic activity), accessibility to healthy food, academic stress and lack of knowledge on nutrition. Two factors emerged from the interviews, one, there was no display in the dining facility about the nutritional value of the food served; and, second, students preferred to dine out on unhealthy food rather than at the university because food from outside the campus , even though unhealthy, was easier on the pocket. Conclusion: The study provides insights into the role of UDF in serving healthy and nutritional food to students for better health and improved academic performance. This work brings to light the relationship between students’ food choices and their impact on academic performance.",
"keywords": [
"Food choices",
"university students",
"campus",
"university dining facility (UDF)",
"qualitative research",
"healthy food",
"theory of planned behavior",
"food transition."
],
"content": "Introduction\n\nSeveral students use hostel facilities offered by their colleges and universities while pursuing higher education. During their stay, their lifestyle undergoes a significant transformation from what they are used to at homes. A crucial change is witnessed in their food habits.4 Rather than eat at the campus, they prefer to eat out at the relatively cheaper options around the campus. This lack of nutritional food is one of the top six causes of health-risk behaviors reported among university students.5\n\nA report by WHO (2015a) states that ‘Healthy diets optimize growth and development over the short- and long-term. They are characterized by being sufficient and balanced in quantity and quality, containing a diversity of nutrient-dense foods including vegetables, fruits, whole grain cereals, fish, legumes, nuts, modest amounts of animal-source foods, limited in foods and drinks high in saturated and trans fats, added sugars and salt”.1 A past study2 has reported that WHO guidelines in respect to dietary habits are rarely practiced by students during their stay at the campus. A study conducted in Kansas in the USA found that a majority of the university students were obese and that their dietary habits needed to be changed to include more nutritional foods rich in fruits, vegetables, and fiber3 Further, the study also recommended physical activity for the students. Consumption of a low proportion of fruits and vegetables and a high proportion of food having high calories, saturated fats, alcohols, and added sugar was reported among large number of university students.6 Many studies in the past have pointed out that university students don’t follow nutritional-rich lifestyles.7 Further, students find process of choosing food challenging,4 hence, they gradually move away from healthy food habits.5 Studies also show that only 4% of students consume 30% or less of energy from fat and 10% or less from sugar per day.3 Hence, there is pressing need to inculcate healthy eating habits amongst the students especially in the face of the upsurge in lifestyle diseases. There is an urgent need to inspire nutrient-rich food behaviors amongst the students such that they select whole grains over processed food, include of fruits and vegetables in their daily diet and avoid health-compromising food choices.9\n\nA review study in the Indian context revealed that a substantial percentage of young people have unhealthy food habits that affect their overall progress. The issues of failure in achieving academic goals are on a rise, mostly interconnected to unhealthy food habits and are likely to intensify in the future. This study considers prime unhealthy habits as “under and over nutrition, common mental issues, non-communicable diseases (NCDs), and stress and anxiety commonly associated with current “nutrition and epidemiological transition”.10\n\nThe present study attempts to apply Ajzen’s (1991) theory of planned behavior to understand and conceptualize how students can transition their food choices to the more healthy options in the university campus. The theory of planned behavior (TPB) was proposed by Icek Ajzen in 1985 and is one of the most applied models to study the intentions and consumer behavior in various setting including food consumption.11 The TPB states that behavior is influenced by intention to participate in that specific behavior (consuming healthy food) and perceived control behavior (PCB), for instance, practicing healthy food consumption at the campus irrespective of the environment. Intentions drive people to take conscious steps to perform a behavior. PCB is the ability of a person to control their behavior, in line with Bandurs’ concept of self-efficacy.12 Terry et al., conducted a study among 146 undergraduate students using regression analysis and found that past behavior experiences (feedback) considerably foretell both, intentions and actual behavior.13 In the present qualitative study, participants had to compulsorily subscribe to UDF during their first year of undergraduate program as per university policy. The same policy was not applicable to postgraduate students. The duration for which students practiced process of choosing food (food choices) from first year onwards and development of feedback initiating repeat behavior was adopted as an approach to study past behaviors (experiences). This study is unique in that it applies the qualitative approach to the subject. In contrast, existing research has only applied the quantitative approach to study food consumption behaviors.14\n\n\nMethods\n\nA private university in Udupi was selected as basis for this study since it has four UDFs on its campus. This university attracts students from all over the country with varied food habits. Second, it was compulsory for first year students to dine at the UDF. This one-year period and the consecutive years thereafter were considered as integral to develop feedback on UDF food. Accordingly, the first-year and post-graduate students of the university formed part of this study. This research employed the qualitative research method and interpretive phenomenologic approach to analyze data and glean insights. The snowball sampling method was applied to recruit participants. An in-depth interview method was used to gather data and glean more subjective views. The interviewer did not know the participants personally. Students of the engineering college were contacted first and requested to participate in study. As the inclusion criteria, they had to be residents of the university accommodation, with their age ranging from 18 to 24 years and pursuing year II through year IV of their study programs. The first year students pursuing undergraduate programs were excluded from the study. First, a few participants were selected by purposive sampling who then recommended other potential participants from their WhatsApp groups. Undergraduate students from years II through IV and post-graduate from years I and II of their study program were invited to participate in the study via their WhatsApp groups. Their participation was voluntary, their verbal consent was taken for participation, and the interview time was confirmed in advance. The participants were not involved in the study beyond data collection and transcripts were only discussed with the research team.\n\nThe ethics clearance certificate was obtained from Kasturba Medical College and Kasturba Hospital Institutional Ethics committee before recruiting the participants for the study. An in-depth interview guide was prepared and validated by doctoral committee for PhD study and experts from nutrition, culinary arts, and qualitative research fields. A pilot study was conducted to test the interview guide and based on the findings, the necessary modifications were incorporated. Participants’ consent was verbal as they were interviewed online via the MS Teams platform and the interaction was audio-recorded based on their consent. Online interviews were conducted with twenty-six students belonging to various regions of India and living on the campus. Data was collected until saturation. Two students couldn’t participate because they had to appear for their examinations. Only, the research team was present during the online interviews with students who were at their own place of residence due to the pandemic lockdown.\n\nThe interviews were conducted in English and then transcribed. Using deductive approach, the codes were identified and grouped under code families. The data were coded manually15 and analyzed by thematic analysis using the Atlas.ti data management software. Coding was performed by the primary researcher and one other research team member. Following this, the codes were reviewed by the research team. Coded data were grouped according to relevance to enlist categories. This helped us to create themes and sub-themes. The themes derived were discussed with the research team members and consistency between data and findings was established.\n\n\nResults\n\nThe demographic profile of the participants revealed that students were pursuing courses in engineering, architecture, medicine, dental, pharmacy and forensic medicine. Their age ranged between 18 to 24 years and most belonged to Mumbai, Kolkata, Ahmadabad, Karkala, Ghaziabad, Bangalore and Kochi. Figure 1 shows the conceptual model of the food choices of the students that emerged after data analysis.\n\nThe conceptual model was developed by applying the theory of planned behavior. It included the following components 1. Individual behavior beliefs 2. Normative beliefs 3. Control beliefs 4. Actual controls, and 5. Feedback. The continuous interdependency and relationship of beliefs about UDF food by participants led to attitude development towards healthy food which, in turn, initiated the transition in intentions to opt for UDF food followed by actual behavior. This cyclic process was observed throughout their stay at campus including the effect of feedback on behavior (food choice) and, accordingly, transition in food choices. Each component of the conceptual model is described using examples from data.\n\n\nIndividual behavioral beliefs\n\nIndividual behavior beliefs were developed based on participants’ experience with respect to their food consumption routines, knowledge about healthy food, views on nutrients requirements, perceptions about the after-effects of adopting unhealthy food choices and their observations of food choices of their peers. Individual beliefs motivated the development of attitude and intention to adopt healthy food choices.\n\nThe data analysis established that all the participants were aware of the need to consume healthy food and practiced healthy food consumption whenever possible. P10-“I eat almonds. I have a box of almonds in my room, so I eat that when I am hungry or when I am studying, like maybe 20 – 30 I eat” …. Data sample also showed that students made a conscious effort to add fruit and vegetable juices, almonds, boiled eggs or omelets, idly, and dosa (rice-based breakfast items) to their diet. P11, “I have tried to make sure I take juice, or I go to the market and buy an apple, grapes or pineapple. When I became really conscious about my health, then I used to have oats.”\n\nData also showed that UDF also served non-vegetarian food items (fish and chicken) as a protein source. Further, it also served vegetable juices, dals (pulses) based curries, and rice-based items in its main meals. P13-“The only reason I tolerate the mess dal is that I need proteins. And in the morning we get upma, bread/butter, dosa, idli and all these things. So carbs are there. And fibers, it’s mostly we get fibers when we eat fruits. And if I get a glass of milk I get my vitamins there.” Our data confirmed that the students were aware of the importance of consuming nutrient-rich food, and how important this was to keep healthy and achieve academic success. They also had a positive attitude towards UDF and the food it served because it included nuts, fruits, vegetables, and proteins.\n\nData analysis revealed that participants were well aware of the fact that the UDF served “balanced and wholesome meals”. P7-“I prefer fresh food, freshly cooked food”\n\nP8-“For daily nourishment, I prefer the mess (UDF) food. So I actually try to eat my meals in the mess (UDF), as much as possible, because they provide quite a wholesome diet”.\n\nOur interactions with the students revealed that they made a conscious attempt to consume fresh fruits and nuts along with meals, avoid food from restaurants, junk food/fast food, ready-to-eat food, and fried food. Besides, they also perceived rice to be healthier than noodles. However, they lacked knowledge about the nutritional value of the food items and this was a barrier in adopting healthy food practices.\n\nFood consumption habits of peers greatly affected individual food choices. Our data confirmed the belief that the peers made unhealthy food choices based more on taste than the actual nutritional value of the food. Peer influence had a great role to play in developing the food culture at the campus. P3-“In my friend circle, there are only 20 to 30% students who are really conscious, and about I would say 30 to 40% are at least a little conscious about healthy food.” Around 60% of the population was indifferent to nutrient rich food and mostly consumed food based on taste, accessibility and convenience (quick service food). P4-“They go more for the taste, they want more spicy gravies or more paneer or more of pasta. Something tastier, and they don’t care if the food is nutritional or not. It has to be tasty, this is a primary objective.” The campus population was categorized into different groups based on their food behavior. About 20-25% peers inconsistently practiced healthy food habits, followed a certain diet, exercised regularly but preferred cheat diets on weekends. About 10-12% peers practiced strict diets, regularly participated in physical activity followed fad diets, but were found to be consuming fewer nutrients than required. P 20-“My experience now people are becoming health conscious, some people are fitter and there are others who starve themselves, and take less nutrients. This generation doesn’t know, they don’t know how much the body needs, how much intake is required, how to take it, and they lack this information”. Our data confirmed that there was an unhealthy food culture in the campus, mainly attributable to lack of proper knowledge and guidance about healthy food, and partly because many believed it to be part and parcel of campus life. Our data also showed that athletes or students involved in sports activities consistently practiced nutritious diet irrespective of their surroundings.\n\nThe participants expressed that during their first and second year of college they preferred to dine at the UDF because it served healthy and nutrient-rich food. P11-“There was this stage when I was into healthy food. But then, exams come and one month before exams, I had to start studying, so I stopped caring for my diet.”\n\nThe participants expressed that their dietary habits took a turn for the worse as they progressed through they college life burdened with their increased academic responsibilities. Their lives became more disorderly leaving them little time to concentrate on their food habits and choices. P9- “I rarely get to sleep. My sleep schedule is … I sleep after 3 or 4 a.m. I eat some snacks like peanuts, or I eat noodles or a sandwich, or just have coffee”. The lifestyle changes were induced by academic stress, time devoted to extracurricular activities, and long working hours, among other factors. P15-“Once I started eating dry fruits in the morning, however, with such busy schedules, on most days I just forgot to take them. But as we got more classes, we started missing more lunch breaks and it got more messed up. So that is why I had to start eating outside at odd hours.”\n\nP3-“I would drink milk daily. But my breakfast pattern has changed a lot since the last year, because I am so heavily involved in so many activities. I really don’t have the time to think about food and what I am eating.” Our data, thus, confirmed that the food habits were greatly impacted by factors such as busy schedules, working at odd hours, skipping meals, high cost of healthy food, and accessibility to healthy food. On the other hand, cheap unhealthy food was easily available and so students gradually transitioned to adopting unhealthy food habits. P5-“Healthier options are more expensive and they are less tasty. So, I think students prefer food items that are both cheap and tasty.” P3-“The majority of the food I eat is for relaxation. That’s why I don’t bother about nutrition.”\n\nThe students also followed undisciplined sleeping and wakening patterns and as a result, they either missed having breakfast or ended up picking up RTE (Ready to Eat) food on the way to their classes or activities. P4-“Students usually skip breakfast because they wake up late. If they have to rush for class, they will pick up a roll, or a packet of biscuits or a packet of chips”. Thus, factors influencing their food choices included academic stress, examination stress, lack of disciplined lifestyle, desire to experience new foods, convenience, financial constraints, easily accessibility of unhealthy foods, inclination to consume non-vegetarian food, and lack of accessibility to outlets offering healthy foods in comparison to the unhealthy options.\n\n\nNormative beliefs\n\nParticipants’ normative beliefs of subjective norms to promote healthy food behavior on campus included university policy, parental influence, and environmental influence. The subjective norms were seen to have positive impact students’ favorable attitude towards the UDF.\n\nParticipants expressed that the university conducted awareness programs on adopting healthy food habits and culture. P2-“1 am gaining some knowledge about nutrient contents of various food items. 2. We gain knowledge about specific nutrients that we benefit from these foods, 3. We need to educate the people about the nutrients we should consume.”\n\nStudents expressed that it would help if the university made some changes to the food offered at the UDF based on their nutrient quality and taste. This would help to develop a positive attitude towards UDF.\n\nP15- “Then a little bit of motivation required from our side only, some motivation is required for us to eat fruits and take juices etc.”\n\nParticipants also expressed that they were aware of lifestyle diseases like diabetes and obesity that are now prevalent amongst young people and mostly caused by unhealthy dietary habits. P9-I think it’s the diseases, it’s the health problems that everyone is getting. I think it is quite visible in the young generation. People are getting diabetes, or obesity problems and many hormonal problems also. And I think it’s the eating habits. I think the only solution to this is to have at least the basic nutrition in our food. Students also expressed that it would greatly help if the university regularly sent out notifications to motivate students to adopt healthy food habits. P20-“How much nutrients body needs, some people take too much some people take less. The authorities must inform us that this is a requirement and this is the way to get it. Actually nobody knows, nobody calculates, how much intake is required. May be making charts, making dining at the mess (UDF) mandatory would help. Outside food we should not consider, this food has this much nutrition, your body needs this, make posters, charts, PPTs to create awareness.” Participants also believed enriching junk food with nutrients could help to kill two birds with one stone, that is, achieve nutrient value without compromising on taste. P17-“We have to increase nutrients in junk food (laugh), students will eat.” Further, improving taste and quality of the UDF food would motivate transition to healthy food.\n\nParental influence\n\nParticipants expressed that parents had a great role to play in influencing their food consumption habits. P9-“At home we can all get nutrition. Because when we are in the hostel, not everything is accessible. So while we were there, if we just have some biscuits that are sugary, like Milkbikis or something, at home we have an option to choose. My dad has turned me into a more nutritional-conscious person.” Parental influence from childhood to adulthood has a great role to play in inculcating healthy food habits for life.\n\nP6-“Because my mother has made sure I have almonds daily since I went to school so I have almonds in my hostel room. I eat regularly, Almonds or pistachio.”\n\nP4-“I mean, there are more different kinds of vegetables at home. At home there are more kinds of sabzis (vegetables) and so we don’t consume chips and such stuff.”\n\nEnvironmental influence\n\nParticipants further expressed that the university could leverage social media to promote healthy food culture in the campus environment. P9-“Some socially active programs or something can help. Maybe they should be attractive enough to draw attention. Some innovative messaging is required.”\n\nThey also felt that student clubs can play a more proactive role in this direction through education, awareness and listing facilities outside the campus where they could purchase healthy food at reasonable rates. P9-“I think, when I actually see that there is a place where we can access food, I think I would try it. I think young people would.”\n\nParticipants realized the importance of physical activity along with consuming healthy food.\n\n\nControl beliefs\n\nThe preconceived notions about food greatly influenced the students’ transitional journey towards healthy food irrespective of peer pressure and their social circle during their stay at the campus.\n\nIt was observed that some of the respondents were not distracted by their immediate environment and maintained steady food habits. P18-“Everyone is going for junk food, but I think there are still some people who are health conscious.” Several respondents were alive to the importance of adopting healthy food habits to improve their academic performance. P15-“We have full-days of classes and we need to maintain our energy levels. And when you tend to eat healthily, you fall less sick. So it is also very important to maintain good health.”\n\nCommenting on why some students were indifferent to eating healthy, P3 said, “It depends on their interests. If they think that their fitness is a priority, then automatically they will be conscious.”\n\nP5-“I participate in events and competitions, I do ultra-running, like 60 km. So, I trained as an athlete, long distance. I never skipped vegetables.”\n\nAccording to the participants, sports people and athletes were more prone to make healthy eating choices because for them winning was at stake. Their determination to win was a motivation to exhibit disciplined food consumption behavior.\n\nStudents were aware that their university campus offered several food outlets comprising of university dining facilities and other food joints or canteens selling both freshly cooked food and ready to-eat food (RTE), along with confectionary. P15-“When you are under stress you tend to binge eat. You buy whatever you get, the available packet food or whatever you are craving for.” Participants also admitted that they were dependent on the other food joints when they were unable to dine at UDF. Usually, for late-night snacks participants frequently visited retail outlets as they were closer to their hostels.\n\nMost participants expressed that they were pressed for time due to their over busy schedules. As a result, they consumed whatever they could easily lay their hands on rather than go out of the way to hunt for high nutrient food. P19-“College timings, how far is college, if we have immediate class after lunch, then we cannot go out, these factors affect what we eat, and so we end up eating some egg roll, that should happen only once a while actually.”\n\nPost-data analysis showed that students were hard-pressed for time because they were far too focused on their studies, preparing for exams, and late night study to better their performance. Further, all these factors together affected their sleeping and waking habits. As a result, they had little time to prioritize their health and healthy eating habits.\n\nActual controls include means to accomplish behavior. Our data analysis showed that students were faced with budget constraints and lack of easy accessibility to healthy food outlets. Actual controls influenced their intentions to practice healthy food habits.\n\nThe students also expressed that budget was a constraint and so they didn’t have adequate funds to purchase high quality, nutrient-rich food. So they preferred to dine at the UDF during the last week of the month and explore other food options around the campus for rest of the month. P12-“When out of money, I eat over there (UDF).”\n\nP5-“Healthier options are more expensive or less tasty. So, I think students focus on taste rather than nutritive value.”\n\nOur data analysis showed that students believed that nutritious food was heavy on their pockets and so they preferred to buy the unhealthy options available. Second, taste was another deciding factor motivating purchase of non-healthy food.\n\nParticipants also expressed that unhealthy options were more readily available near he campus than the healthy ones. P9-“If there is shop having healthy snacks nearby the place of residence, I think I would try it.” P15-UDF provides a proper balanced diet, but people opt out of the mess (UDF) because the food is not that tasty.” For them, UDF was the only facility offering healthy food within their budget. They opined that if the UDF improved the taste and quality of the food it served, they would gladly transition to healthy eating.\n\n\nFeedback on UDF (post-behavior)\n\nThe Theory of Planned Behavior (Ajzen, 1991) describes “Feedback” as the post-behavior understanding of the actions taken (Behavior). Studying the current problem from the lens of the theory of planned behavior, it was found that the students displayed their intention choose UDF over other sources to access healthy food based on feedback.\n\nExamination of data testified that the UDF served nutrition-rich food, a fact that was confirmed by the respondents. P21-“Because they have divided nutrition of everything, they are performing their duties well.” While the UDF offered a balanced diet, the respondents expressed their concerns about the small portions of protein-rich food items that were served and the fact that the facility did not disclose the nutritive value of the foods that could add to their awareness. P24-“Whatever they provide in mess (UDF) is nutritive. They provide dals and lentils which are nutritive. It’s completely fine, the food is nutritive.”\n\nA few participants doubted the credibility of the UDF perceiving it as more business-oriented and comprising quality for cost. P7- “What they are mainly trying to do is to cut costs wherever they can. So it is not exactly for the students benefit.”\n\nThe students expressed their dissatisfaction with the UDF for not disclosing the nutritive values of the food it served the preparation methods it followed, and the absence of a nutritionist who could provide the necessary advice. As a result, these students preferred to dine out than in the facility. However, on the whole, a majority of the respondents were satisfied by the food and services provided by the UDF.\n\nSensory beliefs of food from UDF\n\nParticipants expressed their dissatisfaction with the sensory experience the UDF food provided, expressing that it lacked taste. P15-“The mess people provide properly balanced diet, but people opt out of the mess because of the taste. So if the taste factor is improved, people might stay with the mess and get some nutritious food.”\n\nMost participants agreed that UDF food needs improvement. They found the curries to be too oily, the food lacked spices, the quality of chapattis was poor, and there were too many potatoes and less greens in the menu.\n\n\nDiscussion\n\nThe conceptual model developed for this study is in line with the theory of planned behavior (Ajzen, 1991), and grounded in the students’ perspectives about the UDF food and their own food choices. The model represents a comprehensive process of transition in food choices as they progressed through their stay at the campus. On an average, the students stay in the campus for two to four years and during this time their food habits undergo a change. Their behavioral beliefs, subjective norms and preconceived control beliefs impact their attitude towards UDF and their perceptions about the quality of the food it serves. In the first year, the students are required to dine at the UDF, post which they begin to explore outside options driven by several factors. This is substantiated by the respondents who expressed that they dined at the UDF during the first two years of their study after which many of them explored other options. Most respondents expressed their dissatisfaction with the taste, and this was one of the primary causes for their exploring other avenues even though they served unhealthy food.21 While the food lacked in nutrition it served as a source of relaxation. This finding was in line with another study.22 It was also found that taste was a major factor driving transitions in food habits. Further, the study also found that taste as a sensory experience varied from one person to another.22 Thus, taste is unique to each person and so it is difficult to identify which food has higher sensory attributes. Hence, sensory appreciation cannot be a means to predict acceptance of a certain food item.23\n\nIn line with past studies, the current study also found that the factors that impacted food choices were taste,27,28 price,16 time availability,17,18 convenience, academic stress,18 lack of knowledge about nutrition,19,30 absence of display boards notifying nutrient content of each meal,31 and cheap cost of unhealthy food17 compared to healthy foods.6 However, the study adds new factors to the literature, namely, the concern expressed by the respondents in terms of lack of nutritionist at the UDF to guide and advice about the food served at the UDF, and their lack of knowledge on how the food was actually prepared at the facility. The students also expressed their concerns on the lack of other outlets selling healthy food at the campus. The reasons for deviation from healthy food choices were uniform irrespective of their year of study, education stream, and gender.6 Further, the study also finds that the UDF needs to evolve its services, guided by the administration, and develop a healthy food culture on the campus that is appreciated by the students.20 This recommendation is in line with past research, which emphasized the role of UDF as, “responding to young adult’s food preferences, food service cost-effectiveness, efficiency, and student’s health considerations”.32\n\nThe participants expressed their concerns about the UDF which prompted them to explore other eating options. The theory of planned behavior (Ajzen 1991) states that feedback is necessary to bring about the necessary behavioral changes based on current behavior.11 The conceptual model aptly illustrates the transition in food choices. According to this theory, “background factors,” such as age, education, religion, income, general attitude and emotions etc. indirectly influence a person’s intentions and behavior by effecting behavioral, normative and control beliefs. The data analysis draws insights on study program duration as one of the background factors which stimulated participants’ intentions and behavior towards food choices. The study finds that the respondents were positively disposed toward changing their attitudes and adopting healthy food habits. This is in line with other studies that have found that intentions are a precursor for accomplishing a particular behavior. Success in accomplishing behavior will not be impacted by the will or intention to perform the behavior but also by other control factors, such as requisite chances and means. These requisite chances, means and intention to perform behavior influence a successful transition towards the desired behavior.27 This is well-illustrated in the conceptual model in which these controls are in the form of volitional controls and budgetary constraints affecting students’ intentions and behavior.\n\nThe study establishes a relationship between a healthy environment and healthy food choices24 in which the environment facilitates the accessibility and consumption of fruits, vegetables and nutrient-rich food.25 Students could be made aware of the need to consume healthy foods and display the nutritive value chart of the foods served in the UDF in the facility itself. Further, affirmative messages can be shared regularly in the form of posters, charts, digital boards flashing PPTs through social media and other messaging platforms, and other outreach activities.26 Similar findings were noted in other studies also.33\n\nThe model was conceptualized developed based on the in-depth understanding achieved through the study and not the scale of sample. To achieve this, specific university students from diverse regions and studying at same university campus were invited to share their food experiences. The sample did not aim to represent the students’ population; rather, it was aimed to identify the factors that motivated them to change their food choices over the period of their stay at the campus. Our study sample included students from varied social backgrounds and exposed to different food cultures, with the aim to understand their food transition journeys. The model components display food events held throughout the duration of their stay and the role of feedback in developing an attitude. Future works can consider participants belonging to different universities, geographical locations, and educational streams. An insight on significance of UDF and its role in a students’ transitional food journey was not exclusively objective-oriented but emerged through food events or actions experienced by participants. However, the role of UDF may vary depending on the geographical location of the university.\n\n\nConclusion\n\nThe conceptual model developed to understand food choices focuses on food actions undertaken by individual participants, the interaction of actions with one another and their impact on formation of an individual’s attitude towards healthy food consumption. The developed model offers insights to decision-makers in universities on how they can motivate students towards healthy foods, thereby improving their academic performance. Further, the UDF also needs to evolve its services in tune with the nutritional needs of the students without compromising on taste or adding to their costs. Past studies have shown that a conducive environment promotes healthy food habits. The universities can ensure an ideal environment by ensuring easy availability and accessibility to healthy foods.6,25 The conceptualized model projected in the paper is a first of its kind attempt to understand what governs students’ food choices. Further, research can consider diverse participants in diverse settings.\n\nFood habits studies are multidimensional, individualistic and circumstances-oriented4 for which specific theory or perspective may not be possible. The participants in the present study were students from technical and health science programs representing a small cross-section of the actual student population in the university. As students’ progress to final years of graduation program they tend to live in off-campus apartments.34 These students too were not considered in the study and can be subject to future research. Another limitation of the study was that the interviews were carried out online, and we may have missed the opportunities provided by face-to-face interactions.\n\n\nData availability\n\nFigshare. DataPerceptions.docx. DOI: https://doi.org/10.6084/m9.figshare.20766088.v135\n\nThis project contains the following underlying data:\n\n- Data is transcribed interviews.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).",
"appendix": "Acknowledgement\n\nThe authors would like to thank PhD Doctoral committee members for their constant support and suggestions. We thank Mr. Chirag Kirpalani for his support in transcribing the interviews. We also wish to thank the students for participating in the study.\n\n\nReferences\n\nHawkes C, Fox E, Downs SM, et al.: Child-centered food systems: Reorienting food systems towards healthy diets for children. Glob. Food Sec. April 2021; 27(27): 100414. Publisher Full Text\n\nSadia A, Strodl E, Khawaja NG, et al.: Understanding eating and drinking behaviours in Pakistani university students: A conceptual model through qualitative enquiry. Appetite. July 2020; 161(161): 105133. PubMed Abstract | Publisher Full Text\n\nHuang TTK, Harris KJ, Lee RE, et al.: Assessing overweight, obesity, diet, and physical activity in college students. J. Am. Coll. Health Assoc. 2003; 52(2): 83–86. PubMed Abstract | Publisher Full Text\n\nSobal J, Bisogni CA: Constructing food choice decisions. Ann. Behav. Med. 2009; 38: 37–46. PubMed Abstract | Publisher Full Text\n\nBrunt AR, Rhee YS: Obesity and lifestyle in U.S. college students related to living arrangemeents. Appetite. 2008; 51(3): 615–621. PubMed Abstract | Publisher Full Text\n\nGreaney ML, Less FD, White AA, et al.: College Students’ Barriers and Enablers for Healthful Weight Management: A Qualitative Study. J. Nutr. Educ. Behav. 2009; 41(4): 281–286. PubMed Abstract | Publisher Full Text\n\nGeorgiou CC, Betts NM, Hoerr SL, et al.: Among young adults, college students and graduates practiced more healthful habits and made more healthful food choices than did nonstudents. J. Am. Diet. Assoc. 1997; 97: 754–759. PubMed Abstract | Publisher Full Text\n\nOlson A, Vieyra K, Polasky A, et al.: Nutritional Quality of Undergraduate Student Meals in an All-You-Care-to-Eat Campus Dining Facility (P04-156-19). Curr. Dev. Nutr. 2019; 3(Supplement_1): 367. Publisher Full Text\n\nMcDermott MS, Oliver M, Svenson A, et al.: The theory of planned behaviour and discrete food choices: A systematic review and meta-analysis. Int. J. Behav. Nutr. Phys. Act. 2015; 12: 162. PubMed Abstract | Publisher Full Text\n\nSunitha S, Gururaj G: Health behaviours & problems among young people in India: Cause for concern & call for action. Indian J. Med. Res. 2014; 140: 185–208. PubMed Abstract\n\nConsumer attitudes and behavior: the theory of planned behavior applied to food consumption decisions. Riv. Econ. Agrar. 2015.\n\nArmitage CJ, Conner M: The theory of planned behaviour: Assessment of predictive validity and “perceived control”. Br. J. Soc. Psychol. 1999; 38(1): 35–54. Publisher Full Text\n\nTerry DJ, O’Leary JE: The Theory of Planned Behaviour: The Effects of Perceived Behavioural Control and Self-Differences Personality and Social Efficacy. Br. J. Soc. Psychol. 1995; 34: 199–220. Publisher Full Text\n\nZoellner J, Krzeski E, Harden S, et al.: Qualitative Application of the Theory of Planned Behavior to Understand Beverage Consumption Behaviors among Adults. J. Acad. Nutr. Diet. 2012; 112(11): 1774–1784. PubMed Abstract | Publisher Full Text\n\nBasit TN: Manual or electronic? The role of coding in qualitative data analysis. Educ. Res. 2003; 45(2): 143–154. Publisher Full Text\n\nGrossiey ML, Khan SN: Motives underlying food choice: Dentists, porters and dietary health promotion. Br. Dent. J. 2001; 191(4): 198–202.\n\nChambers S, Lobb A, Butler LT, et al.: The influence of age and gender on food choice: A focus group exploration. Int. J. Consum. Stud. 2008; 32(4): 356–365. Publisher Full Text\n\nPapier K, Ahmed F, Lee P, et al.: Stress and dietary behaviour among first-year university students in Australia: Sex differences. Nutrition. 2015; 31(2): 324–330. PubMed Abstract | Publisher Full Text\n\nKeith JF, Stastny S, Brunt A, et al.: Barriers and Strategies for Healthy Food Choices among American Indian Tribal College Students: A Qualitative Analysis. J. Acad. Nutr. Diet. 2018; 118(6): 1017–1026. PubMed Abstract | Publisher Full Text\n\nRoy R, Soo D, Conroy D, et al.: Exploring University Food Environment and On-Campus Food Purchasing Behaviors, Preferences, and Opinions. J. Nutr. Educ. Behav. 2019; 51(7): 865–875. PubMed Abstract | Publisher Full Text\n\nHuang YL, Song WO, Schemmel RA, et al.: What do college students eat? Food selection and meal pattern. Nutr. Res. 1994; 14(8): 1143–1153. Publisher Full Text\n\nFurst T, Connors M, Bisogni CA, et al.: Food choice: A conceptual model of the process. Appetite. 1996; 26(3): 247–266. PubMed Abstract | Publisher Full Text\n\nPollard TM, Steptoe A, Wardle J: Motives underlying healthy eating: Using the food choice questionnaire to explain variation in dietary intake. J. Biosoc. Sci. 1998; 30(2): 165–179. PubMed Abstract | Publisher Full Text\n\nLiberato SC, Bailie R, Brimblecombe J: Nutrition interventions at point-of-sale to encourage healthier food purchasing: A systematic review. BMC Public Health. 2014; 14(1): 1. PubMed Abstract | Publisher Full Text\n\nDavis Hearn M, Baranowski T, Baranowski J, et al.: Environmental influences on dietary behavior among children: Availability and accessibility of fruits and vegetables enable consumption. J. Health Educ. 1998; 29(1): 26–32. Publisher Full Text\n\nGreene GW, Schembre SM, White AA, et al.: Identifying Clusters of College Students at Elevated Health Risk Based on Eating and Exercise Behaviors and Psychosocial Determinants of Body Weight. J. Am. Diet. Assoc. 2011; 111(3): 394–400. PubMed Abstract | Publisher Full Text\n\nSchifter DE, Ajzen I: Intention, Perceived Control, and Weight Loss. An Application of the Theory of Planned Behavior. J. Pers. Soc. Psychol. 1985; 49(3): 843–851. PubMed Abstract | Publisher Full Text\n\nBoek S, Bianco-Simeral S, Chan K, et al.: Gender and Race are Significant Determinants of Students’ Food Choices on a College Campus. J. Nutr. Educ. Behav. 2012; 44(4): 372–378. PubMed Abstract | Publisher Full Text\n\nTam R, Yassa B, Parker H, et al.: University students’ on-campus food purchasing behaviors, preferences, and opinions on food availability. Nutrition. 2017; 37: 7–13. PubMed Abstract | Publisher Full Text\n\nNavia B, Ortega RM, Requejo AM, et al.: No Title. Eur. J. Clin. Nutr. 2003; 57(1): S90–S93. Publisher Full Text Reference Source\n\nCioffi CE, Levitsky DA, Pacanowski CR, et al.: A nudge in a healthy direction. The effect of nutrition labels on food purchasing behaviors in university dining facilities. Appetite. 2015; 92: 7–14. PubMed Abstract | Publisher Full Text\n\nHoracek TM, Yildirim ED, Kelly E, et al.: Development and validation of a simple convenience store SHELF audit. Int. J. Environ. Res. Public Health. 2018; 15(12): 1–16.\n\nLowry R, Galuska DA, Fulton JE, et al.: Physical activity, food choice, and weight management goals and practices among U.S. college students. Am. J. Prev. Med. 2000; 18(1): 18–27. PubMed Abstract | Publisher Full Text\n\nSmall M, Bailey-Davis L, Morgan N, et al.: Changes in Eating and Physical Activity Behaviors Across Seven Semesters of College: Living On or Off Campus Matters. Health Educ. Behav. 2013; 40(4): 435–441. PubMed Abstract | Publisher Full Text\n\nVishwakarma K, Patwardhan V, Sekaran VC, Kamath A: DataPerceptions.docx. figshare. Dataset.2022. Publisher Full Text"
}
|
[
{
"id": "225157",
"date": "28 Nov 2023",
"name": "Rajshri Roy",
"expertise": [
"Reviewer Expertise Public Health Nutrition - Obesity - Diet - Food Environment Interventions - Dietary Behaviour Change - Young Adults - Health Promotion - Social Marketing - Implementation Science - Nutrition Assessment - Nutritional Epidemiology - Dietary Patterns - eHealth/mHealth - Qualitative Research - Translational 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\nStudy Design and Setting: The choice of a private university in Udupi with four University Dining Facilities as the study setting is rational given its diverse student population and the compulsory dining policy for first-year students. This allows for a broad range of data on food choices over time.\nParticipants: The study focuses on a specific age group (18-24 years) and academic years (II-IV for undergraduates, I-II for postgraduates), which provides a clear scope. However, the exclusion of first-year undergraduates raises questions since their experiences with UDFs in their compulsory dining year could provide valuable insights into initial food choice behaviors.\nSampling Method: Using snowball sampling for participant recruitment is common in qualitative studies, particularly when exploring specific behaviors within a defined community. The use of purposive sampling to initiate the snowball sampling process is appropriate, though there is a potential for bias as the initial subjects could influence the sample's homogeneity.\nData Collection: The in-depth interview method is suitable for exploring the subjective aspects of food choice. The assurance that the interviewer did not have a prior relationship with the participants helps mitigate bias. However, the study would benefit from clarifying the interview questions or providing an appendix or supplementary file with the interview guide to assess the relevance and comprehensiveness of the questions.\nData Saturation: The article should state if the data reached saturation, meaning no new themes were emerging from the interviews.\nQuantitative Data: If any quantitative measures were used to supplement the qualitative data, these should be presented to strengthen the findings. Analytical Rigor: While thematic analysis is mentioned, more information on how themes were derived and validated would add to the credibility of the results.\nThe discussion and conclusion are well-aligned with the results, contribute to the academic conversation with new insights, and are presented clearly and accurately with appropriate citations. The authors are candid about the limitations of their work and suggest avenues for future research, which adds to the credibility of 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? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNot applicable\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "10968",
"date": "21 Oct 2024",
"name": "Varalakshmi Chandra Sekaran",
"role": "Author Response",
"response": "Dear Reviewer, thank you for the suggestions to improve our article. Study Design and Setting: The choice of a private university in Udupi with four University Dining Facilities as the study setting is rational given its diverse student population and the compulsory dining policy for first-year students. This allows for a broad range of data on food choices over time. Thank you for this observation. Participants: The study focuses on a specific age group (18-24 years) and academic years (II-IV for undergraduates, I-II for postgraduates), which provides a clear scope. However, the exclusion of first-year undergraduates raises questions since their experiences with UDFs in their compulsory dining year could provide valuable insights into initial food choice behaviors. First year students were excluded from study- At the time of conduct of the study, newly enrolled students were not yet 18 years of age and did not fit the inclusion criteria. They begin with experiencing food at campus and need few months to develop their feedback. Sampling Method: Using snowball sampling for participant recruitment is common in qualitative studies, particularly when exploring specific behaviors within a defined community. The use of purposive sampling to initiate the snowball sampling process is appropriate, though there is a potential for bias as the initial subjects could influence the sample's homogeneity. Thank you for this observation. The study employed purposive sampling initially followed by snowball sampling. Data Collection: The in-depth interview method is suitable for exploring the subjective aspects of food choice. The assurance that the interviewer did not have a prior relationship with the participants helps mitigate bias. Thank you for this observation. An additional statement is made in the revised manuscript by declaring no relationship was present with participants prior to the study. Data Saturation: Data saturation statement is added in the methodology Analytical Rigor: While thematic analysis is mentioned, more information on how themes were derived and validated would add to the credibility of the results. This is included in the last paragraph of the methodology. The development of themes was by an iterative process, with coding followed by categorization into sub-themes and finally into themes."
}
]
},
{
"id": "218221",
"date": "28 Nov 2023",
"name": "Dimitris Skalkos",
"expertise": [
"Reviewer Expertise Food business management of innovation"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nThe manuscript is badly written even though the research work can be considered as interesting.\n\nThe manuscript should be rewritten with the following remarks:\n1. Introduction: Recent citations should be use and not old since 2000! As two examples: . FOR REVIEW OF FOOD CHOICE MOTIVES: “Exploring the Impact of COVID‐19 Pandemic on Food Choice Motives: A Systematic Review” D.Skalkos, Z.C. Kalyva, Sustainability, 15, 1606, 1-16, https://doi.org/10.3390/su15021606\n\n2023\n. FOR STUDENTS' FOOD CHOICES: “The impact of the COVID-19 pandemic on college Students’ food choice motives in Greece” D.Skalkos, Z.C. Kalyva, I.S. Kosma, Sustainability, 15, 9865, 1-11, https://doi.org/10.3390/su15139865\n\n2023 Literature is full of related publications the last 3 years!!\n2. Results: The answers of the participants should be presented in a numerical form and table(s) in order for the results to be presented correctly The questionnaire itself should be presented in an appendix form\n3. Discussion: As with the introduction recent references of related work should be used and not such as 16 (2001), 17 (2008), 27 (1985), 28 (2012) etc.\nMy recommendation is: ACCEPTED AFTER MAJOR REVISIONS\n\nIs the work clearly and accurately presented and does it cite the current literature? No\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nNo\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "10967",
"date": "21 Oct 2024",
"name": "Varalakshmi Chandra Sekaran",
"role": "Author Response",
"response": "Dear Reviewer, thank you for the suggestions to improve our article. Introduction: Recent citations should be used and not old since 2000! The mentioned changes are done in the manuscript and highlighted. Results: 1. The answers of the participants should be presented in a numerical form and table(s) for the results to be presented correctly 2. The questionnaire itself should be presented in an appendix form A qualitative method was applied for the study hence numerical tables were not added in the paper. The questionnaire is included in the revised transcript. Earlier questionnaire was submitted with a separate DOI Discussion: As with the introduction recent references of related work should be used and not such as 16 (2001), 17 (2008), 27 (1985), 28 (2012), etc. Changes are made in revised draft."
}
]
}
] | 1
|
https://f1000research.com/articles/11-1192
|
https://f1000research.com/articles/13-339/v1
|
23 Apr 24
|
{
"type": "Research Article",
"title": "Prevalence of psychological distress: a scientific approach towards the mental health and wellbeing of population during the SARS-COV-2 outbreak",
"authors": [
"Saman Tauqir",
"Inayat Shah",
"Ahmed Alsubaie",
"Sara Noreen",
"Shazia Sadaf",
"Saqib Ali",
"Saman Tauqir",
"Inayat Shah",
"Ahmed Alsubaie",
"Sara Noreen",
"Shazia Sadaf"
],
"abstract": "Background The global challenge of the novel coronavirus has led to an unprecedented downturn, adversely affecting the health and mental wellbeing of communities worldwide. The objective of this study is to assess mental health and psychological distress levels within the general population of Peshawar, Pakistan amidst the ongoing COVID-19 pandemic.\n\nMethod A cross-sectional online study was conducted among 715 individuals residing in Peshawar city, Pakistan. A questionnaire containing details about demographics, socioeconomic status, and residential area was employed. To assess the mental wellbeing of participants a Modified K10, Kesslers psychological distress Scale was used. Descriptive statistics, including mean and standard deviations, were utilized for data analysis. Statistical analyses were performed using Statistical Package for Social Science (SPSS, IBM USA,version 22).\n\nResults A total of 715 responses were collected. The comprehensive psychological distress score was identified as 25.55, signifying moderate stress levels. Among the respondents, 53.3% were females, 46.7% had completed a bachelor’s degree, 41% were employed, 78.7% were single, 93.1% were non-smokers, and 69.4% resided in urban areas. The study revealed that both gender (p=0.001) employment status (p=0.018) were linked to a more pronounced psychological impact of the outbreak.\n\nConclusions The present study indicates that age, gender, employment status, and urbanization are influential factors contributing to psychological distress during the outbreak. As we confront the challenges of the new normal, it is crucial for policymakers to acknowledge and tackle the growing mental health concerns within the population.",
"keywords": [
"COVID-19",
"Kesseler scale",
"SARS-CoV-2",
"Mental health",
"Pandemic",
"Pakistan"
],
"content": "Inroduction\n\nThe emergence of Coronavirus Disease 2019 (COVID-19) in Wuhan, China, in December 2019 swiftly escalated into a global pandemic within months.1 The consequences of this public health crisis have significantly impacted the mental well-being of the population, giving rise to a surge in psychological crises.2,3 Identifying populations experiencing early-stage psychological crises is crucial for the effective implementation of intervention strategies. Despite a widespread increase in mental distress reported among both the general public and frontline medical personnel, the specific determinants of psychological distress remain unidentified across the diverse populations affected by the COVID-19 pandemic.2,3,4\n\nTraumatic public health emergencies can induce feelings of insecurity, driven by the fear of infection and mortality. Symptoms such as anxiety, stress, insomnia, and fear are frequently observed during pandemics.5 Various studies conducted during the pandemic have reported increased psychological distress in the general population and a significant proportion of healthcare professionals.6,7 The fear of infection, economic downturn, job losses, vaccination and reduced income due to prolonged lockdowns are collectively contributing to mental health disorders in society, ultimately leading to depression and suicidal thoughts.3,8,9\n\nThe mental health implications of the COVID-19 pandemic are of paramount importance, affecting the general population on multiple fronts.10,11 Our frontline heroes, including all medical professionals directly engaged with COVID-19-infected and quarantined patients, endure constant and substantial psychological trauma.10 Stress predictors for these individuals include persistent fears of contracting the virus, overwhelming workloads, and the emotional toll of witnessing COVID-19 patients passing away in isolation.11\n\nIt is crucial to acknowledge and address the psychological traumas and mental health challenges faced by individuals in the wake of the pandemic. Implementing measures like lockdowns, while necessary for control, can induce anxiety responses and contribute to increased fear and prejudice against those infected or affected.12 Studies examining the impact of COVID-19 on mental well-being not only shed light on critical areas of concern but also offer insights into how healthcare services can be equipped with essential information and support to provide mental health treatment to those in need.13 Consequently, prioritizing public mental health is paramount, necessitating the adaptation of policies to support individuals in navigating the challenges posed by the “new normal.” The primary objective of this study is to assess mental health and psychological distress levels within the general population of Peshawar, Pakistan amidst the ongoing COVID-19 pandemic.\n\n\nMethods\n\nThe research design employed for this study was cross-sectional, conducted among the population of Peshawar city Pakistan using an online survey. The survey was distributed to the public through diverse social platforms, including WhatsApp, Twitter, emails, and Facebook messengers.\n\nApproval for ethical considerations was granted by the Ethics Review Committee of the Khyber Medical University (approval number: DIR/KMU-EB/PS/000109, granted on 02-02-2022). This study was conducted conferring to declaration of Helsinki. Written informed consent was obtained from participants via a consent statement for participation incorporated before the survey, stating, “Your involvement in this study is entirely voluntary. There are no anticipated risks associated with this project. However, if you find any questions uncomfortable, you have the option to withdraw from the survey at any point.” Thus, participation in the survey was considered as implicit consent to participate.\n\nSurvey participants encompassed individuals of both genders, aged between 15 and 60, and representing various educational backgrounds. The study targeted individuals with internet access, encompassing a diverse group, including undergraduate students, engineers, medical professionals, government employees, retirees, lawyers, business professionals, and individuals from various other professions. Prior to survey completion, informed consent was obtained from all participants, and their responses were kept confidential and anonymous. The survey took approximately five to seven minutes to finish.\n\nData collection for this study utilized an online survey conducted through Google Forms. The questionnaire for this study was structured into sections, covering demographic characteristics (gender, education level, marital status, job status and area of residing whether urban or rural).\n\nFor assessing distress, K10 was used which serves as a concise screening method to assess various levels of distress. The Kessler Psychological Distress Scale (K10) is a straightforward tool for gauging psychological distress.14 Comprising 10 questions regarding emotional states, each with a five-level response scale.\n\nScoring for each item ranges from one, indicating ‘none of the time,’ to five, indicating ‘all of the time.’ The scores for the 10 items are then totaled, resulting in a minimum score of 10 and a maximum score of 50. Lower scores suggest minimal psychological distress, while higher scores indicate elevated levels of psychological distress.\n\nIn terms of score interpretation, cut-off scores as a reference for screening psychological distress are as follows:15\n\nK10 Score: Likelihood of having a mental disorder (psychological distress)\n\n10-19: Likely to be well\n\n20-24: Likely to have a mild disorder\n\n25-29: Likely to have a moderate disorder\n\n30-50: Likely to have a severe disorder.\n\nDescriptive statistics, including mean and standard deviations, were utilized for data analysis. Statistical analyses were performed using Statistical Package for Social Science (SPSS, IBM USA,version 22), applying one-way ANOVA based on the number of groups and items to be compared. Results were presented as means and ± Standard Deviation SD, and differences were deemed statistically significant if p≤0.05. This comprehensive methodology ensured a rigorous and systematic approach to understanding the mental health dynamics in the specified population during the challenging times of the COVID-19 pandemic.\n\n\nResults\n\nThe study included 715 respondents, reflecting a diverse participant profile (Table 1). The overall psychological distress score averaged 25.55, indicating a moderate level of stress. Key sociodemographic characteristics revealed that the majority of participants were female (53.3%), held a bachelor's degree (46.7%), were employed (41%), single (78.7%), non-smokers (93.1%), and resided in urban areas (69.4%).\n\nTable 2 presents the psychological responses of the respondents to the Kessler scale during the lockdown in Peshawar, Pakistan. Analyzing the data from Table 2, it is observed that 22.7% (162 respondents) reported feeling tired most of the time in the last month, with 7% (50 respondents) expressing constant fatigue over the 30-day period. Approximately 15.9% (114 respondents) noted feeling nervous most of the time during the pandemic, while 30.3% (217 respondents) experienced occasional nervousness. Conversely, 2.7% (19 respondents) reported constant nervousness throughout the pandemic. Furthermore, 10.1% (72 respondents) felt uncalmable during the past month, whereas 41.4% (296 respondents) indicated a sense of calmness, suggesting adaptation to the new normal. Unfortunately, 6.6% (47 respondents) felt hopeless about the ongoing situation, while 35.5% (254 respondents) remained hopeful for improvement. Additionally, 31% (222 respondents) experienced restlessness at times, and 25.9% (185 respondents) felt so restless that they could not stand still. Finally, 19.6% (140 respondents) reported feeling depressed most of the time, and 7.7% (55 respondents) expressed constant depression due to the outbreak of the viral disease. These findings provide a comprehensive understanding of the psychological responses of the participants during the specified period, shedding light on the multifaceted impact of the COVID-19 pandemic on mental well-being.\n\nTable 3 presents the mean values and corresponding standard deviations of each question on the Kessler Scale 10, which measures psychological distress. The data provides insights into the frequency and intensity of various stress-related parameters among the surveyed individuals in Peshawar, Pakistan during the COVID-19 pandemic. Additionally, the table includes the 95% confidence intervals of the mean differences, offering a statistical perspective on the reliability of the reported values.\n\nA comparison of Kessler Scores across different demographic factors, exploring the determinants of stress among the surveyed individuals is presented in Table 4. It shows the mean values, standard deviations, and p-values for various demographic categories. The Kessler scores of females were found to be significantly higher than those of male participants (27.36 vs. 23.48, p = 0.001). Similarly, employed participants exhibited higher scores compared to their non-employed counterparts (25.72 vs. 22.47, p = 0.018), suggesting potential variations in stress levels based on gender and employment status Table 4.\n\nThis table provides an overview of the demographic distribution of survey participants, including percentages and frequencies. The categories encompass age groups, gender, location, smoking habits, marital status, and profession. The legend offers a comprehensive understanding of the respondents' diverse characteristics and backgrounds.\n\nThis table presents the detailed responses of participants to Kessler’s questions, each assessed on a 5-point Likert scale ranging from “None of the time” to “All of the time.” The parameters tested include feelings of tiredness, nervousness, hopelessness, restlessness, depression, and worthlessness. The legend provides a breakdown of participant responses across various levels of frequency for each parameter, offering insights into the mental well-being of the surveyed individuals.\n\nThis table displays the mean values and standard deviations of each question in the K10 assessment. The parameters tested include feelings of tiredness, nervousness, hopelessness, restlessness, depression, and worthlessness. Additionally, the 95% confidence intervals of the differences are provided, offering insights into the variability of responses and the overall mental health assessment based on the participants' mean scores for each parameter.\n\nTable 4 reveals that females Kessler score was significantly higher than male participants (27.36 vs 23.48, p – 0.001). Similarly, the score was higher in employed participants (25.72 vs 22.47, p – 0.018). However, living in Urban and Rural site (25.84 vs 24.81, p – 0.127).\n\n\nDiscussion\n\nIn our cross-sectional study, we sought to dissect the effects of the COVID-19 pandemic on the mental health of the population in Peshawar Pakistan. The study's results reveal a significant impact of the COVID-19 pandemic on the mental health of individuals in Peshawar, Pakistan. The detailed psychological responses during the lockdown underscore the multifaceted nature of the pandemic's impact, encompassing fatigue, nervousness, feelings of hopelessness, and varied experiences of restlessness and depression.\n\nThe study reports an overall psychological distress score of 25.55 suggesting moderate level of stress among the diverse group of 715 respondents. Notable gender disparities were observed, with females exhibiting significantly higher distress scores than males (27.36 vs 23.48, p=0.001) (Table 4). Employed individuals demonstrated higher distress scores (p =0.018) (Table 4). In line with our results a studies in Nepalian populations and population of the United Kingdom reports high stress during the pandemic suggesting that there is a crucial need to carry out psychological interventional programs to cope with the situation effectively.16,17\n\nOur study reports the stress score of 27.36 in females indicating moderate stress levels. These findings are in line with the findings of a study conducted by Farooq et al.18, revealing that females exhibited 2.5 times higher levels of stress compared to males (39.4% vs. 23.3%, respectively) (Table 4). Another investigation found that the prevalence of depressive symptoms were 66% among women, contrasting 33% among men.19 Globally conducted studies, including those in China,1 India,20 and Spain,21 support these findings by reporting elevated stress symptoms among females. Recently Qiu et al., reported from China that the female gender and younger population were at a higher risk for different mental health outcomes and suffered from anxiety and stress.22,23 These findings are also in line with another cross-sectional study carried out in Turkey which also reported that the group most affected psychologically by the pandemic were females, and the urban population. Priority might therefore be attached to these in future psychiatric planning.5 Similarly, an Iranian study also reported the high prevalence of stress and depression among the females (95%) of Iranian during the pandemic.24 Plausible explanations for the heightened prevalence of stress in women include biological factors, socioeconomic disadvantages, a loss of social status, maladapted coping strategies, and a lack of support systems in the country.25 Additionally, socio-cultural norms in Pakistani households often lead women to juggle both household and professional responsibilities, while men are typically less involved in domestic activities. The ‘stay home, stay safe’ policy during the pandemic has intensified the workload for women as men spend more time at home.\n\nThese findings could be of great use in proposing new policies for global mental health related problems during the new normal.\n\nEmployment status also played a role, as employed individuals demonstrated higher distress scores compared to their unemployed counterparts (25.72 vs 22.47, p =0.018) (Table 4). Anticipated salary cuts and a decline in job opportunities, coupled with heightened uncertainty and potential fear, may contribute to an increase in stress.12 Furthermore, the closure of offices due to travel restrictions has resulted in a shift to remote work for most employees. The lack of in-person interaction with colleagues could impact workers' motivation, job satisfaction, and overall productivity.12,26 The inability to meet deadlines and achieve targets, compounded by the added responsibilities of managing household affairs, may elevate anxiety levels among employees.12\n\nThe SARSCoV-2 2019 is a highly contagious virus spreading via droplets or direct contact. Such viruses are transmitted easily in urban areas compared to rural areas with thick populations.27 Therefore, a higher prevalence of mental distress is evident in both urban and semi-urban settings. This may be attributed to the increased incidence of COVID-19 in urban areas, where the lockdown has significantly impacted densely populated cities throughout Pakistan, effectively putting the lives of their residents at risk.28,29 Our study reports a greater psychological impact of the virus on the individuals living in urban areas 25.8 (Table 4) having access to communication and latest chaos caused by pandemic reporting. The results are corroborated by a Chinese investigation that demonstrated a higher occurrence of psychological health issues among individuals residing in urban areas. This trend is attributed to the substantial number of COVID-19 cases concentrated in cities, with urban areas serving as epicenters of the disease.30\n\nDeveloping countries face different challenges providing e-mental health care services due to lack of useful online interventions.31 Responsible organizations of the country should design and enforce a gender-sensitive psychosocial protocol in form of videos or phone calls to ensure mental wellbeing in the nation. NGOs are efficient and effective mode to be used in this regard because of their close relation with communities, therefore they should be brought to proper use in this area.\n\n\nConclusion\n\nIn conclusion, our cross-sectional study in Peshawar, Pakistan, reports a moderate overall psychological distress score of 25.55 indicates a noteworthy level of stress among the diverse group of 715 respondents. Notable gender disparities highlight that females exhibit significantly higher distress scores than males. Employment status also plays a role, with employed individuals demonstrating higher distress scores. Urban areas, acting as epicenters of the disease, experience a higher prevalence of mental distress, emphasizing the urban-rural divide in the impact of the virus. Our study provides a platform for the policy health care policy makers of our country to prioritize mental health issues in the time of new normal.\n\nWhile our study provides valuable insights into the psychological state during the “new normal,” it is essential to acknowledge its limitations. The survey's cross-sectional nature limits our ability to make conclusions regarding the long-term effects of the pandemic, representing a notable study limitation. Additionally, potential selection bias exists as the survey relied on an online questionnaire, excluding individuals without Internet access or those unable or unwilling to use smartphones and emails.\n\nFuture research, particularly among healthcare workers and their families, is recommended to further explore the profound mental health impact within this high-risk group. Measures therefore should be taken to psychologically support these citizens of the state. There is a need to carry out psychological interventional activities through various mediums like web videos, e-massages, advertisements, and mental helpline services to help people become more resilient during the COVID-19 pandemic. The government should take time sensitive decisions and steps to introduce e-mental health to reduce mental stress in the time of pandemic.",
"appendix": "Data availability\n\nFigshare: Prevalence of psychological distress: A Scientific approach towards the mental health and wellbeing of population during the SARS-COV-2 outbreak. https://doi.org/10.6084/m9.figshare.24638121.v1. 32\n\nThis project contains the following underlying data:\n\n• data (2).xlsx\n\nFigshare: Prevalence of psychological distress: A Scientific approach towards the mental health and wellbeing of population during the SARS-COV-2 outbreak. https://doi.org/10.6084/m9.figshare.24638121.v1. 32\n\nThis project contains the following extended data:\n\n• kessler.pdf (copy of questionnaire)\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 extend their thanks to the participants.\n\n\nReferences\n\nZhang J, Lu H, Zeng H, et al.: The differential psychological distress of populations affected by the COVID-19 pandemic. Brain Behav. Immun. 2020; 87: 49–50. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlam BF, Almojaibel AA, Ansari KA, et al.: General public awareness, knowledge and attitude toward COVID-19 infection and prevention: A cross-sectional study from Pakistan. F1000Res. 2021; 10: 10. Publisher Full Text\n\nAlqarawi FK, Alam BF, Nayab T, et al.: Impact of COVID-19 on the self-esteem, psychological and dental esthetics of dental students. Work. 2023; (Preprint): 1–10.\n\nKhan SQ, Moheet IA, Farooqi FA, et al.: Will Physical Distancing Be the New Perceived Way of Life in the Post-Covid-19 Pandemic Era? J. Med. Sci. 2023; 31(01): 55–61. Publisher Full Text\n\nÖzdin S, Bayrak ÖŞ: Levels and predictors of anxiety, depression and health anxiety during COVID-19 pandemic in Turkish society: The importance of gender. Int. J. Soc. Psychiatry. 2020; 66: 504–511. Publisher Full Text\n\nTan W, Hao F, McIntyre RS, et al.: Is returning to work during the COVID-19 pandemic stressful? A study on immediate mental health status and psychoneuroimmunity prevention measures of Chinese workforce. Brain Behav. Immun. 2020; 87: 84–92. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang C, Pan R, Wan X, et al.: A longitudinal study on the mental health of general population during the COVID-19 epidemic in China. Brain Behav. Immun. 2020; 87: 40–48. Publisher Full Text\n\nMcIntyre RS, Lee Y: Projected increases in suicide in Canada as a consequence of COVID-19. Psychiatry Res. 2020; 290: 113104. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAli S, Khan U, Iqbal K, et al.: Acceptance of Covid-19 Vaccine among the Residents of Karachi, Pakistan. J. Med. Sci. 2022; 30(04): 311–319. Publisher Full Text\n\nThakur V, Jain A: COVID 2019-suicides: A global psychological pandemic. Brain Behav. Immun. 2020; 88: 952–953. Publisher Full Text\n\nReger MA, Stanley IH, Joiner TE: Suicide mortality and coronavirus disease 2019—a perfect storm? JAMA Psychiatry. 2020; 77: 1093–1094. PubMed Abstract | Publisher Full Text\n\nUllah I, Ali S, Ashraf F, et al.: Prevalence of depression and anxiety among general population in Pakistan during COVID-19 lockdown: An online-survey. Curr. Psychol. 2022; 43: 8338–8345. Publisher Full Text\n\nÖzdin S, Bayrak ÖŞ: Levels and predictors of anxiety, depression and health anxiety during COVID-19 pandemic in Turkish society: The importance of gender. Int. J. Soc. Psychiatry. 2020; 66(5): 504–511. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAndrews G, Slade T: Interpreting scores on the Kessler psychological distress scale (K10). Aust. N. Z. J. Public Health. 2001; 25(6): 494–497. PubMed Abstract | Publisher Full Text\n\nKessler RC, Green JG, Gruber MJ, et al.: Screening for serious mental illness in the general population with the K6 screening scale: results from the WHO World Mental Health (WMH) survey initiative. Int. J. Methods Psychiatr. Res. 2010; 19(S1): 4–22. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSamadarshi SCA, Sharma S, Bhatta J: An online survey of factors associated with self-perceived stress during the initial stage of the COVID-19 outbreak in Nepal. Ethiop. J. Health Dev. 2020; 34(2).\n\nChelidoni O, Berry C, Easterbrook MJ, et al.: Predictors of COVID-19 anxiety in UK university students. J. Furth. High. Educ. 2023; 47(3): 421–434. Publisher Full Text\n\nFarooq S, Khan T, Zaheer S, et al.: Prevalence of anxiety and depressive symptoms and their association with multimorbidity and demographic factors: a community-based, cross-sectional survey in Karachi, Pakistan. BMJ Open. 2019; 9(11): e029315. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZahidie A, Jamali T: An overview of the predictors of depression among adult Pakistani women. Journal of the College of Physicians and Surgeons Pakistan. 2013; 23(8): 574–580. PubMed Abstract\n\nVarshney M, Parel JT, Raizada N, et al.: Initial psychological impact of COVID-19 and its correlates in Indian Community: An online (FEEL-COVID) survey. PLoS One. 2020; 15(5): e0233874. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGonzález-Sanguino C, Ausín B, Castellanos MÁ, et al.: Mental health consequences during the initial stage of the 2020 Coronavirus pandemic (COVID-19) in Spain. Brain Behav. Immun. 2020; 87: 172–176. PubMed Abstract | Publisher Full Text | Free Full Text\n\nQiu J, Shen B, Zhao M, et al.: A nationwide survey of psychological distress among Chinese people in the COVID-19 epidemic: implications and policy recommendations. General psychiatry. 2020; 33(2): e100213. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang C, Pan R, Wan X, et al.: Immediate psychological responses and associated factors during the initial stage of the 2019 coronavirus disease (COVID-19) epidemic among the general population in China. Int. J. Environ. Res. Public Health. 2020; 17(5): 1729. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMoghanibashi-Mansourieh A: Assessing the anxiety level of Iranian general population during COVID-19 outbreak. Asian J. Psychiatr. 2020; 51: 102076. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFisher J, Mello MC, Patel V, et al.: Prevalence and determinants of common perinatal mental disorders in women in low-and lower-middle-income countries: a systematic review. Bull. World Health Organ. 2012; 90: 139–149H. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKarobari MI, Marya A, Ali S, et al.: A multicultural demographic study to evaluate the impact of the SARS-CoV-2 pandemic on the job satisfaction across the dental industry. Pesqui. Bras. Odontopediatria. Clin. Integr. 2022; 21: e210137. Publisher Full Text\n\nChoi J, Taylor S: The psychology of pandemics: Preparing for the next global outbreak of infectious disease. Newcastle upon Tyne, UK: Cambridge Scholars Publishing. Asian Communication Research; 2020; 17(2): 98–103.\n\nChen Y, Jin Y, Zhu L, et al.: The network investigation on knowledge, attitude and practice about COVID-19 of the residents in Anhui Province. Zhonghua yu Fang yi xue za zhi [Chinese Journal of Preventive Medicine]. 2020; 54(4): 367–373. PubMed Abstract | Publisher Full Text\n\nAli S, Tauqir S, Alam BF, et al.: COVID-19 knowledge, attitude and awareness among preclinical and clinical dental students: An online-based cross-sectional survey. Journal of Oral Research. 2021; 10(3): 1–9. Publisher Full Text\n\nLiu L, Xue P, Li SX, et al.: Urban-rural disparities in mental health problems related to COVID-19 in China. Gen. Hosp. Psychiatry. 2021; 69: 119–120. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYao H, Chen J-H, Xu Y-F: Rethinking online mental health services in China during the COVID-19 epidemic. Asian J. Psychiatr. 2020; 50: 102015. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAli S: Prevalence of psychological distress: A Scientific approach towards the mental health and wellbeing of population during the SARS-COV-2 outbreak. Dataset. figshare. 2023. Publisher Full Text"
}
|
[
{
"id": "272714",
"date": "31 May 2024",
"name": "Niaz Ali",
"expertise": [
"Reviewer Expertise Social Science",
"Pharmacology",
"Medical Education",
"Dental Education",
"Psychological"
],
"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 is done extensively and is of interest but it needs major revisions so it can be of greater benefit for the community. Please find my detailed comments below. All the very best. 1. Please check the manuscript for grammatical errors and typos. Some sentences are too long to follow. 2. Consider refining the use of passive voice where possible, to active voice, which can make the abstract more engaging and easier to read. 3. Ensure consistency in statistical reporting, for example, always use the same number format for p-values (e.g., p < 0.001 or p = 0.001). 4. If space allows in the body of the article, it would be valuable to include more detailed analysis or discussion about the impact of COVID-19 on different age groups or between genders. This can provide deeper insights into which sub-groups are most vulnerable. 5. In the recommendations, besides general calls for policy action, suggest specific mental health resources or programs that have been effective in similar contexts. 6. Ensure all references are up to date and correctly formatted, and check if the latest statistics or studies might provide more recent insights into the COVID-19 impact on mental health globally and locally. 7. The abstract provides a solid overview of your research and its importance to public health discourse in Pakistan. By tightening the focus a bit more on specific actionable insights and perhaps providing a bit more context about the tools and demographic influences, it can serve as a robust entry point for readers into the study's full 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? 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": "12606",
"date": "21 Oct 2024",
"name": "Saqib Ali",
"role": "Author Response",
"response": "Dear Reviewer Many thanks for the constructive feedback. We have addressed all the comments suggested and improved the manuscript per your suggestions which are as below: The study is done extensively and is of interest but it needs major revisions so it can be of greater benefit for the community. Please find my detailed comments below. All the very best. 1. Please check the manuscript for grammatical errors and typos. Some sentences are too long to follow. Response: Thank you for your feedback regarding grammatical errors and sentence structure. We will thoroughly review the manuscript for any typos and grammatical mistakes to ensure clarity and accuracy. Additionally, we will revise overly long sentences to improve readability and ensure that the flow of ideas is smooth and easy to follow. In particular, we will focus on breaking down complex or lengthy sentences into shorter, more concise ones where possible. This will help make the content more accessible to readers and improve the overall presentation of the manuscript. 2. Consider refining the use of passive voice where possible, to active voice, which can make the abstract more engaging and easier to read. Response: We will review the abstract carefully and rephrase sentences in active voice wherever appropriate. For example, rather than saying, \"Data was collected from participants,\" we can change it to, \"We collected data from participants.\" This adjustment will help create a more direct and dynamic tone, making the content easier to follow and more compelling. 3. Ensure consistency in statistical reporting, for example, always use the same number format for p-values (e.g., p < 0.001 or p = 0.001). Response: Thank you for pointing out the need for consistency in statistical reporting. We will review the manuscript to ensure that all statistical values, particularly p-values, follow a uniform format throughout (e.g., consistently using \"p < 0.001\" or \"p = 0.001\"). This will improve the clarity and professionalism of the presentation. 4. If space allows in the body of the article, it would be valuable to include more detailed analysis or discussion about the impact of COVID-19 on different age groups or between genders. This can provide deeper insights into which sub-groups are most vulnerable. Response: Thank you for your suggestion to expand the analysis on the impact of COVID-19 across different age groups and genders. We agree that a more detailed examination of how various demographic sub-groups are affected could provide valuable insights into which populations may be more vulnerable to psychological distress. If space permits in the body of the article, we will include an analysis that breaks down the mental health impacts of COVID-19 by age and gender. This could involve examining whether certain age groups, such as older adults or young adults, experience higher levels of anxiety or depression. Additionally, we can explore any gender-based differences in psychological responses, which may help identify specific needs for targeted intervention strategies. 5. In the recommendations, besides general calls for policy action, suggest specific mental health resources or programs that have been effective in similar contexts. Response: Thank you for your suggestion to include specific mental health resources and programs in our recommendations. We agree that mentioning effective programs from similar contexts can provide actionable insights for policymakers and healthcare providers. We will update it. 6. Ensure all references are up to date and correctly formatted, and check if the latest statistics or studies might provide more recent insights into the COVID-19 impact on mental health globally and locally. Response: Thank you for your feedback on ensuring reference accuracy and currency. We will review all references to confirm they are up-to-date and correctly formatted. Additionally, we will search for the latest studies and statistics on COVID-19's global and local mental health impact to provide the most current insights in our discussion. 7. The abstract provides a solid overview of your research and its importance to public health discourse in Pakistan. By tightening the focus a bit more on specific actionable insights and perhaps providing a bit more context about the tools and demographic influences, it can serve as a robust entry point for readers into the study's full findings. Response: Thank you for your feedback. We will tighten the abstract’s focus on specific actionable insights and add brief context about the tools used and demographic influences. These updates will create a clearer and more engaging entry point for readers into our study's findings."
}
]
},
{
"id": "272711",
"date": "11 Jun 2024",
"name": "Aziza Alam",
"expertise": [
"Reviewer Expertise Public Health",
"maternal and Child Health",
"Nutrition",
"Research designs",
"environmental 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 presented study briefly encapsulates the essence of your study on the assessment of mental health and psychological distress within the general population of Peshawar, Pakistan, during the COVID-19 pandemic. Here are some suggestions and comments for potential refinement and further consideration: 1.\n\nIntroduction: It's concise and effectively sets the stage for the study's relevance. You might want to add a brief note on why Peshawar specifically was chosen, if there's a unique context that makes this study particularly important for the region. 2.\n\nExpand Background Context: Provide more background on the mental health impacts of pandemics historically or from recent events prior to COVID-19. This could help frame the significance of your study within a broader context. 3.\n\nMethod: This section is clear about the study's design and tools used for data collection. It could be enhanced by briefly mentioning the rationale behind using the Kessler Psychological Distress Scale specifically, which could help non-specialist readers understand its relevance and validity in this context. 4.\n\nThe conclusion rightly emphasizes the implications for policy. It could be strengthened by explicitly recommending specific policy measures or interventions that could be implemented based on the study findings. 5.\n\nAddress Bias and Generalizability in your limitations. More thoroughly discuss how the method of survey distribution (online) might limit the generalizability of the findings. For instance, does this method potentially exclude older populations or those without internet access?\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": "12607",
"date": "21 Oct 2024",
"name": "Saqib Ali",
"role": "Author Response",
"response": "Dear Reviewer Many thanks for the constructive feedback. We have addressed all the comments and did the modifications accordingly. Please find below the responses to all your comments. Reviewer comment: The presented study briefly encapsulates the essence of your study on the assessment of mental health and psychological distress within the general population of Peshawar, Pakistan, during the COVID-19 pandemic. Here are some suggestions and comments for potential refinement and further consideration: 1. Introduction: It's concise and effectively sets the stage for the study's relevance. You might want to add a brief note on why Peshawar specifically was chosen, if there's a unique context that makes this study particularly important for the region. Author response: Thank you for your positive feedback on the introduction. We appreciate your suggestion to provide more context on why Peshawar was specifically chosen for this study. Peshawar was selected due to its status as a major healthcare hub in Pakistan, hosting several tertiary care hospitals that serve a large and diverse population. The city’s healthcare institutions train a substantial number of dental professionals, including interns and postgraduates, who experience unique challenges and stressors related to their demanding schedules and high patient load. Additionally, factors such as cultural attitudes, lifestyle, and socioeconomic conditions in Peshawar may contribute to sleep disorders in ways that differ from other regions, making it a valuable location for this study. We will incorporate these points into the introduction to highlight the significance of studying sleep disorders among dental professionals specifically in Peshawar, providing a stronger rationale for the study’s relevance to the region. Thank you for this helpful suggestion. Reviewer comment: 2. Expand Background Context: Provide more background on the mental health impacts of pandemics historically or from recent events prior to COVID-19. This could help frame the significance of your study within a broader context. Author response: Thank you for the suggestion to expand the background context by exploring the mental health impacts of pandemics from a historical perspective. This is a valuable idea, as it can help frame the significance of our study within a broader context. Historically, pandemics have had profound impacts on mental health, as observed in past events such as the Spanish Flu of 1918, which led to widespread anxiety, grief, and psychological distress due to high mortality rates and societal disruption. Similarly, during the SARS outbreak in 2003, studies reported increased levels of depression, anxiety, and post-traumatic stress symptoms among healthcare workers and the general population. Research from the Ebola outbreak in West Africa in 2014 also highlighted severe psychological consequences, including stigma, isolation, and an increase in mental health disorders among survivors and healthcare professionals. These historical events demonstrate that pandemics often lead to substantial mental health challenges, including heightened stress, anxiety, and depression, due to factors such as fear of infection, prolonged isolation, and socioeconomic strain. By framing the COVID-19 pandemic within this broader historical context, we can underscore the importance of addressing mental health impacts as an integral part of pandemic response and recovery efforts. We will incorporate this background into the study to emphasize the relevance of examining mental health impacts during pandemics and provide a richer context for our research. Thank you for this insightful recommendation. Reviewer comment: 3. Method: This section is clear about the study's design and tools used for data collection. It could be enhanced by briefly mentioning the rationale behind using the Kessler Psychological Distress Scale specifically, which could help non-specialist readers understand its relevance and validity in this context. Author response: Thank you for your feedback on the methods section. We appreciate your suggestion to include a brief rationale for using the Kessler Psychological Distress Scale (K10) in this study. The K10 scale was selected due to its strong validity and reliability in measuring psychological distress across diverse populations and its sensitivity to detecting symptoms of anxiety and depression. It consists of 10 questions that assess the frequency of emotional states associated with psychological distress, making it an efficient tool for identifying individuals at risk for mental health disorders. The scale is widely used in public health research due to its ease of administration and its ability to provide a quick, standardized measure of distress levels, which is particularly useful in large-scale studies like ours. Including the K10 allows us to accurately quantify levels of psychological distress among participants, enabling comparisons across different groups. This choice is especially relevant for our study, as it provides a validated measure to assess mental health impacts in the context of the pandemic, making the findings more robust and generalizable. We will incorporate this explanation into the methods section to clarify the rationale behind choosing the Kessler Psychological Distress Scale, especially for readers who may not be familiar with the tool. Thank you for the valuable suggestion. Reviewer comment: 4. The conclusion rightly emphasizes the implications for policy. It could be strengthened by explicitly recommending specific policy measures or interventions that could be implemented based on the study findings. Author response: Thank you for your feedback on the conclusion. We appreciate your suggestion to strengthen it by providing specific policy recommendations based on the study’s findings. To make the implications for policy more actionable, we propose to include recommendations for targeted interventions. For example, based on our findings, we can recommend implementing mental health support programs specifically tailored for healthcare professionals, such as stress management workshops, counseling services, and peer support networks within hospitals. Additionally, policies that promote regular screening for psychological distress using tools like the Kessler Psychological Distress Scale could be introduced as part of routine health check-ups for healthcare workers, especially during periods of heightened stress, such as pandemics. Further, workplace policies that encourage reasonable work hours, regular breaks, and sufficient leave days can help mitigate stress and improve overall well-being among healthcare staff. These measures, supported by healthcare institutions and policymakers, could help address and prevent psychological distress more effectively, promoting a healthier, more resilient workforce. We will incorporate these specific policy recommendations into the conclusion to provide a more concrete foundation for translating our findings into practical interventions. Thank you for your helpful suggestion to enhance this section. Reviewer comment: 5. Address Bias and Generalizability in your limitations. More thoroughly discuss how the method of survey distribution (online) might limit the generalizability of the findings. For instance, does this method potentially exclude older populations or those without internet access? Author response: Thank you for highlighting the importance of addressing potential biases and limitations related to survey distribution. We agree that discussing how the online survey method may impact the generalizability of our findings is essential. In the limitations section, we will expand on the potential biases introduced by using an online survey format. Specifically, we recognize that relying on online distribution may exclude certain demographics, such as older individuals who may not be as comfortable with digital technology or those without consistent internet access. This limitation could lead to an underrepresentation of these groups, potentially skewing our findings towards younger, more tech-savvy participants. Additionally, the online format may introduce selection bias, as those experiencing higher levels of psychological distress may be more inclined to participate in a survey on this topic. To improve generalizability in future studies, we recommend complementing online surveys with alternative distribution methods, such as paper surveys or in-person interviews, especially in settings where internet access is limited. By acknowledging these limitations, we aim to provide a balanced interpretation of our findings and offer suggestions for future research to mitigate these biases. Thank you for your valuable suggestion to enhance this aspect of our discussion on study limitations."
}
]
}
] | 1
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https://f1000research.com/articles/13-339
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https://f1000research.com/articles/13-1257/v1
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21 Oct 24
|
{
"type": "Software Tool Article",
"title": "AnVILWorkflow: A runnable workflow package for Cloud-implemented bioinformatics analysis pipelines",
"authors": [
"Sehyun Oh",
"Kai Gravel-Pucillo",
"Marcel Ramos",
"Michael C. Schatz",
"Sean Davis",
"Vincent Carey",
"Martin Morgan",
"Levi Waldron",
"Kai Gravel-Pucillo",
"Marcel Ramos",
"Michael C. Schatz",
"Sean Davis",
"Vincent Carey",
"Martin Morgan",
"Levi Waldron"
],
"abstract": "Advancements in sequencing technologies and the development of new data collection methods produce large volumes of biological data. The Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) provides a cloud-based platform for democratizing access to large-scale genomics data and analysis tools. However, utilizing the full capabilities of AnVIL can be challenging for researchers without extensive bioinformatics expertise, especially for executing complex workflows. We present the AnVILWorkflow R package, which enables the convenient execution of bioinformatics workflows hosted on AnVIL directly from an R environment. AnVILWorkflow simplifies the setup of the cloud computing environment, input data formatting, workflow submission, and retrieval of results through intuitive functions. We demonstrate the utility of AnVILWorkflow for three use cases: bulk RNA-seq analysis with Salmon, metagenomics analysis with bioBakery, and digital pathology image processing with PathML. The key features of AnVILWorkflow include user-friendly browsing of available data and workflows, seamless integration of R and non-R tools within a reproducible analysis pipeline, and accessibility to scalable computing resources without direct management overhead. AnVILWorkflow lowers the barrier to utilizing AnVIL’s resources, especially for exploratory analyses or bulk processing with established workflows. This empowers a broader community of researchers to leverage the latest genomics tools and datasets using familiar R syntax. This package is distributed through the Bioconductor project (https://bioconductor.org/packages/AnVILWorkflow), and the source code is available through GitHub (https://github.com/shbrief/AnVILWorkflow).",
"keywords": [
"Cloud computing",
"Genomics",
"Workflows",
"R/Bioconductor",
"AnVIL"
],
"content": "Introduction\n\nThe NHGRI’s Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL) consortium was launched in 2018, aiming to democratize genomics data.1 AnVIL enables easy sharing of genomics data by organizing databases, bioinformatics pipelines for large-scale data processing, and interactive downstream analysis in one Cloud-based platform. AnVIL,2 also the name of the platform from the AnVIL project, implements the FAIR data-sharing philosophy and provides a graphical user interface (GUI, supported by Terra3), making it more accessible for researchers without programming backgrounds. However, a GUI tends to be less efficient and slower than a command line interface (CLI), especially for bulk analyses, still requires learning a new platform, and does not support version control and text-based workflows, often included as best practices for reproducible computational research.4\n\nBioconductor’s AnVIL package is an AnVIL API wrapper that provides R-friendly, programming-based functionalities to leverage flexible and scalable cloud-based resources implemented in the AnVIL platform. With the AnVIL package, users can easily access workflows, data, and Cloud-based computing resources managed by AnVIL. However, the AnVIL package is not customized for workflow execution tasks. Instead, AnVIL covers all the resources related to the AnVIL platform, such as interaction with the repository for Docker-based genomic analysis tools and workflows (Dockstore5), leveraging cloud resources (Leonardo6), and data search and digestion (Gen37). Many AnVIL functions also expose API commands directly, requiring a deep understanding of the underlying AnVIL workspace structures and data models to use for workflow execution. Also, it is a general package without individual support on any workspace and provides no metadata curation. Because most Bioconductor users focus on data analysis, a convenient R-friendly way of accessing and utilizing AnVIL resources is needed. Here, we present the AnVILWorkflow package to meet this need. AnVILWorkflow package is a convenient, fit-for-purpose wrapper around the AnVIL package with the following features optimized for workflow execution:\n\n• Intuitive function names and returned values\n\n• Support workflow-specific documentations\n\n• Enable to set up a Cloud environment with a single function call\n\n• Return error messages that are easy to interpret and actionable\n\n• Essential metadata curation for more efficient data browsing\n\nUsers can apply AnVILWorkflow on any workspace they can access, including 347 public workspaces (snapshot on 8.28.23) available to anyone with an AnVIL account. We present three use cases where we ran non-R-based bioinformatics analysis tools using conventional R syntax: Salmon,8 bioBakery,9 and PathML.10 Salmon is a widely used RNA sequencing analysis tool for quantifying the expression of transcripts and is based on the command-line interface. Its downstream analysis involves many R/Bioconductor packages, such as DESeq2, edgeR, and limma. bioBakery is a widely used whole metagenomic shotgun (WMS) sequencing data analysis environment, mainly relying on Python. PathML is a general-purpose research toolkit for computational pathology, including many functionalities in digital pathology data analysis, such as strain normalization, nucleus segmentation, and tissue detection. PathML takes raw image files and returns the processed image data in an hdf5 format for further downstream analysis, including machine learning methods.\n\nAnVIL provides comprehensive resources for biomedical data analysis, including data (e.g., genomics), workflows for bulk analysis, and interactive analysis apps (i.e., Galaxy, Jupyter Notebooks, and RStudio) under the workspace. Workflows are often a limiting factor in bioinformatics analysis due to computing demands and the bioinformatics expertise required. Thus, the AnVILWorkflow package makes the workflow-related resources from AnVIL more accessible and easier to use, especially for R users (Figure 1).\n\nAnVIL’s workflow description language (WDL) specified the runtime environment, which includes proper docker containers for existing analysis tools and computing resources. Cromwell, a scientific workflow execution and management system, runs WDL workflows on the cloud. AnVILWorkflow users can easily run established workflows developed by experts and utilize the cloud resources without configuring or taking maintenance responsibilities.\n\nWhile AnVIL manages workflow orchestration and workspace metadata and provides default setups that simplify decision-making for users, users still need to manage their data storage and cloud costs. Genomics data, especially their raw and intermediate forms, are very large, so data storage can be costly if the sample size increases. Storage costs incur and can be managed in two ways - storage itself and transfer. For example, using regional storage instead of multi-region, cleaning up intermediate results, and storing infrequently accessed data in low-cost storage (e.g., nearline or coldline storage from Google Cloud) can reduce per-sample costs. Analyzing data stored in one region using Virtual Machine (VM) compute resources in a different region incurs data transfer charges, so centralizing all storage and computing in a single region can be more cost-efficient by not only reducing the storage cost but also avoiding data transfer charges. Currently, the AnVIL workspaces use the us-central1 as a default region, and any artifacts generated from the workflow execution, unless specified, are saved in the same-region bucket linked to the workspace. If users use the default region configured by AnVIL, bringing their data stored in the default region, us-central1, will save the data transfer charge. Additionally, open and controlled access genomic datasets hosted in AnVIL are stored in the us-multi-region, so there are no storage and transfer charges for users using the default workspace configuration. Downloading data to the user’s workstation or laptop is subject to charges, currently $0.08 to $0.12 per GB, depending on the amount of data11 and geography of the transfer, and transfer from the US to another continent is more expensive than within the US transfer.\n\nWhile browsing existing resources through AnVILWorkflow is free, running workflows charge computing costs. AnVILWorkflow is designed to use existing workflows, which usually predefine computing resources optimized for the types of analyses, simplifying computing-related cost management. You can further reduce the run cost using call caching and preemptive instances. For example, if your workflow runs in fewer than 24 hours since a preemptible VM lasts 24 hours at most, you can save up to 80% by using preemptible VMs.\n\nThe cost management for a group of users can be efficiently managed through the AnVIL billing project. One billing account can be shared by adding email addresses under the billing project. The billing project offers details on each workspace, including workspace owner and spent reports, so we can easily identify ‘who’ uses ‘how much’ for ‘what’. In addition to the workspace-level expense reports, users can further enhance cost monitoring by configuring spending reporting.12 This allows users to closely monitor the expenditure associated with each workflow execution.\n\n\nMethods\n\nAnVILWorkflow package provides all the functionalities required to run workflows available in AnVIL from the local R session - from the environment setup to the output download. One prerequisite is to create an AnVIL account from the AnVIL web portal. AnVIL account provides two required inputs to run workflows remotely: 1) the email address associated with the user’s account and 2) the billing project name to cover the computing cost.\n\nAnVIL-hosted workflows can be run using four main functions: setCloudEnv, cloneWorkspace, runWorkflow, and getOutput. The setCloudEnv function accepts the AnVIL account email and billing project name and sets up your local R environment so you can access AnVIL and Cloud-computing resources. The cloneWorkspace function creates the user’s copy of a ‘template’ workspace, and the runWorkflow executes the workflow. The getOutput function can check the outputs from successfully executed workflows and download user-specified files to a local computer.\n\nUser input can be provided through the updateInput function, which accepts two different forms of tables depending on the workflows - AnVIL’s data model or URLs pointing to data files stored in Google Cloud buckets. The input data formats are already specified in the workflow scripts (Workflow Description Language, WDL13). Other accessory functions are available to monitor submission progress (monitorWorkflow), stop submitted workflow (stopWorkflow), and get Dashboard content (getDashboard).\n\nThe AnVILBrowse function allows users to browse AnVIL resources using keywords. This function runs instantaneously because the AnVILWorkflow package includes the metadata snapshot on all the publicly accessible AnVIL workspaces and their workflows and data. It performs basic metadata harmonization, allowing more efficient browsing and filtering, such as selecting workspaces based on the study size or participants’ ages. Users can also browse non-public workspaces they have access to using the getMetaTables function; however, this process can take a while, depending on the number of workspaces a user has access to.\n\nThe use cases demonstrated below include demo input data in the template workspaces, so the R scripts below can run the listed use cases from the local computer. Ready-to-run examples that can be used to test the process on the user’s own AnVIL account are available in the AnVILWorkflow package vignette. Genome Analysis Toolkit Variant Discovery (GATK) best-practice pipelines14 are not demonstrated here but are also available as AnVIL workspaces.\n\nThe main features of the demo workspaces and their workflow-specific input data preparation process are described below.\n\n\nResults\n\nBulk RNA sequencing data analysis\n\nSalmon workflow uses AnVIL’s data model and requires four essential inputs - fastq1, fastq2, fasta, and transcriptome index name. This workflow can be easily applied to the consortium data hosted in AnVIL, which follows AnVIL’s data model. With the default runtime environment configured for this workflow (1 CPU, 2GB memory, and 10GB SSD disk), processing 16 demo samples (32 fastq files, ~1 GB per file) took about 30 minutes and cost $0.12.\n\nWhole metagenomic shotgun data analysis\n\nbioBakery is a metagenome analysis environment composed of Python-based tools, reference databases, and command-line-based workflows. It processes raw shotgun sequencing data into microbial community feature profiles, summary reports, and figures.9 bioBakery’s whole metagenome shotgun (wmgx) and visualization (wmgx_vis) workflows are implemented as an AnVIL workspace. The current version of the AnVILWorkflow supports bioBakery version 3.15 While users can customize this workflow to a great degree, only six inputs are sufficient to run a standard, optimized version of this workflow. Those six inputs are:\n\n- Name of the Trimmomatic adaptor type (for demo data, NexteraPE)\n\n- Your project name\n\n- Extension of input files (for demo data, .fastq.gz)\n\n- A table of your sequencing file (fastq) names stored in the Google Cloud Storage bucket\n\n- Input file identifier for paired-end sequencing (for demo data, _R1 and _R2)\n\nThe seven required databases are already linked to this workflow, and nine additional optional inputs are available for further customization. Optional inputs are for workflow customization, such as bypassing functional profiling (default is false) and maximum memory usage for different tasks (default is 32GB for functional profiling by HUMAnN, 8GB for quality control by Kneaddata, and 24GB for taxonomic profiling by MetaPhlAn). This workflow uses call caching and preemptive instances by default for cost efficiency. Processing six paired-end demo samples (mean file size ~380MB) with the optimized default setting without using preemptive instances took about 5 hours and cost around $6.50. With the preemptive instances, it can take longer but cost less. Compared to the existing options, such as Nephele,16 AnVILWorkflow allows a programmatic approach and more flexible customization options.\n\nHistopathology image processing using PathML\n\nWe implemented the hematoxylin-eosin (HE) stain normalization process of PathML as an AnVIL workspace. This workflow accepts an SVS file as input and returns original and normalized images as PNG files. There are two required inputs - Google Cloud Storage URI, where the input SVS image file is stored, and the sample name. Processing one publicly available image (CMU-1_Small_Region.svs, 1.8MB)17 with the default runtime (4 CPU, 16GB memory) took about 8 minutes and cost $0.01. This simple but robust analysis setup can support clinical use cases, such as pathologists who process a large number of images in a short time, by offering guidance and cross-validation options.\n\n\nDiscussion\n\nThe AnVILWorkflow package enables users to conduct complex and computationally intense analyses with minimal bioinformatics expertise through well-established workflows within AnVIL and versatile cloud resources directly from standard laptops using the familiar R syntax. The major advantages AnVILWorkflow provides over the existing approaches include 1) a minimal entry barrier, negating the need for software installations, preparation of properly versioned reference data, or construction and oversight of workflows, 2) leveraging flexible cloud computing resources without the need to learn or handle them directly, 3) user-friendly functions that provide enhanced information, and 4) improved reproducibility and interoperability by seamlessly linking multiple analysis steps, conducted in both R and non-R based tools, within a single R vignette. However, there are still some limitations. For instance, certain customizations of the workflows are limited or require a more profound understanding of the workflows. Despite not being inherently more costly than an in-house server, the pay-per-use structure requires careful planning and management. The absence of an integrated versioning system in AnVIL workspaces requires users to manually monitor new versions. In conclusion, AnVILWorkflow proves most advantages for analyzing a bulk of samples on relatively simple workflows (i.e., single-stage workflow procedure) or for exploratory data analysis for non-technical users, particularly when employing well-established analysis workflows.\n\nEthical approval and consent were not required.\n\n\nAuthors’ contributions\n\nSO, LW, and VC conceived the research idea. SO, KG, MR, and MM developed the software. SO and KG performed the benchmarking analyses. SO, LW, and KG wrote the manuscript. LW, SD, MS, and MR reviewed the manuscript.",
"appendix": "Data availability\n\n\n\n• Figshare: Test datasets for bioBakery and PathML workflows; https://doi.org/10.6084/m9.figshare.27018421.v3 18\n\nThe project contains the following underlying data:\n\n- IBDMDB: six pairs of WMS sequencing files and their sample-level metadata\n\n- PathML_data: one input and two output files\n\n• The test datasets for bulk RNAseq analysis workflow have been deposited in the European Nucleotide Archive (ENA); accession numbers are DRR016125-DRR016140; https://www.ebi.ac.uk/ena/browser/view/PRJDB2508 19\n\n• License: Creative Commons Attribution 4.0 International (CC BY 4.0)\n\n\nAcknowledgments\n\nNot applicable.\n\n\nReferences\n\nSchatz MC, et al.: Inverting the model of genomics data sharing with the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-space. Cell Genom. 2022; 2.\n\nTerra. Reference Source\n\nTerra. Reference Source\n\nSandve GK, Nekrutenko A, Taylor J, et al.: simple rules for reproducible computational research. PLoS Comput. Biol. 2013; 9: e1003285. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYuen D, et al.: The Dockstore: enhancing a community platform for sharing reproducible and accessible computational protocols. Nucleic Acids Res. 2021; 49: W624–W632. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLeonardo: Notebook Service: (Github).\n\nHughes L, et al.: Harmonization of clinical data across Gen3 data commons. J. Clin. Orthod. 2019; 37: e18094–e18094.\n\nPatro R, Duggal G, Love MI, et al.: Salmon provides fast and bias-aware quantification of transcript expression. Nat. Methods. 2017; 14: 417–419. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMcIver LJ, et al.: bioBakery: a meta’omic analysis environment. Bioinformatics. 2018; 34: 1235–1237. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRosenthal J, et al.: Building Tools for Machine Learning and Artificial Intelligence in Cancer Research: Best Practices and a Case Study with the PathML Toolkit for Computational Pathology. Mol. Cancer Res. 2022; 20: 202–206. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPricing: Google Cloud.Reference Source\n\nHow much did my workflow cost? Terra Support. http\n\nVoss K, Gentry J, Van der Auwera G: Full-stack genomics pipelining with GATK4 + WDL + Cromwell.2017. Preprint at Publisher Full Text\n\nVan Der Auwera GO, Connor BD: Genomics in the Cloud: Using Docker, GATK, and WDL in Terra. O’Reilly Media; 2020.\n\nBeghini F, et al.: Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3. elife. 2021; 10. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWeber N, et al.: Nephele: a cloud platform for simplified, standardized and reproducible microbiome data analysis. Bioinformatics. 2018; 34: 1411–1413. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAperio SVS. Reference Source\n\nOh S: Test datasets for the AnVILWorkflow package. figshare. 2024. Publisher Full Text\n\nEMBL-EBI: ENA Browser.Reference Source\n\nOh S: AnVILWorkflow. Zenodo. 2024. Publisher Full Text"
}
|
[
{
"id": "342032",
"date": "04 Dec 2024",
"name": "Fabricio Almeida-Silva",
"expertise": [
"Reviewer Expertise Bioinformatics"
],
"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 manuscript, Oh et al present AnVILWorkflow, an R package that allows running and managing AnVIL workflows directly from an R session. This package is a valuable resource for the bioinformatics community, especially to novice bioinformaticians or researchers who are not familiar with the details of AnVIL. AnVILWorkflow has the potential of making AnVIL more widely used and known, simplifying the analysis of biological data and helping decelerate the unnecessary growth of lab-specific bioinformatics pipelines that do (roughly) the same thing. The manuscript is well written, and it nicely describes what AnVIL is, positive and negative aspects, and how to use AnVIL workflows in R. Overall, I believe the manuscript is in great shape in its current format. I have only a few minor points that I believe could help readers:\n(1) Authors mention some approaches to reduce costs, such as using call caching and pre-emptive instances. I believe it would be useful if authors could expand on that, giving clear examples (maybe using one of the three example workflows in the manuscript) on how such cost reductions can be achieved.\n(2) For people who have never used AnVIL before and want to consider using it after reading this paper, I think authors could add a few sentences in the Discussion describing how to set up AnVIL in a lab. For instance, since it works on a pay-per-use basis, should a lab have a single account or should each member of the lab have its own? How should accounts be managed to reduce redundancy and costs?\n(3) The whole idea of AnVIL seems very similar to Galaxy. I know the purpose of this manuscript is to describe AnVILWorkflow, not AnVIL itself, but maybe mentioning Galaxy in the Introduction and how AnVIL differs from Galaxy (highlighting advantages and disadvantages) would be useful to readers.\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": "342030",
"date": "11 Dec 2024",
"name": "Zachary S.L Foster",
"expertise": [
"Reviewer Expertise I am primary a bioinformatic software developer with experience in pathogen diagnostics",
"metabarcoding",
"and developing pipelines. Of relevance to this article",
"I have developed R packages and pipelines that run on commercial cloud services."
],
"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 describe an R package for submitting and interacting with pipelines hosted on the Genomic Data Science Analysis, Visualization, and Informatics Lab-space (AnVIL). The goal of this package is to make it easier for people primarily familiar with R to use AnVIL resources without learning other systems. This is primarily beneficial for those inexperienced in bioinformatics and that need to run large analyses using linux-based tools. The paper is succinct and written well. I appreciate the factual and unbiased tone of the writing. In particular, the lack of exaggeration of the significance of the work is refreshing. The tools itself seems fairly simple and is primarily consists of “quality of life” wrappers for the AnVIL R packages, which seem to more closely follow the implementation of the underlying API. AnVILWorkflow has about 10 commands, each 50-100 lines of R code. The code is well documented and seems tidy, but there are a few minor improvements that could be made, which I mention below. I installed the package from Bioconductor and the few function I tried seemed to work, but I did not run any analyses, since this would require an account or Terra and would cost money. Overall, this article is a nice and succinct description of a tool meant to make running analyses on Terra/AnVIL more user-friendly. Below are specific comments for each section.\nIntroduction\nDefine acronym NHGRI “Enable to set up a Cloud environment with a single function call” sounds off. Maybe “Cloud environment initialization with a single function call.” Should “spent reports” be “spending reports” or “expense reports”? “However, the AnVIL package is not customized for workflow execution tasks.”: The source code for AnVILWorkflow::runWorkflow calls AnVIL::Terra()$createSubmission, so it seems that the AnVIL package does allow for workflow execution. Are you trying to say that it is not as convenient for workflow execution? Might want to rephrase this to make it more clear/accurate.\n\nResults\n“Name of the Trimmomatic adaptor type”: Is this the right phrasing? Trimmomatic is the program used to remove adapters, but is not a type of adaptor. Perhaps something like “Sequencing adaptor type”?\n\nDiscussion\n“Despite not being inherently more costly than an in-house server, the pay-per-use structure requires careful planning and management.”: I like that this comparison is brought up. Cloud based analysis sounds very tempting at first, but I have used it for genomics data analysis and I am not convinced its a way to save money. In fact, I expect that in-house computing is actually cheaper in the long run. A powerful desktop can run the vast majority of bioinformatic workflows. Scaling and massive one-off analyses are the main benefits of cloud computing. Surprise costs are a big problem, especially to those that have little experience in commercial cloud computing, which is the target audience of this article. It might be a good idea to add a stronger warning about surprise costs. I also like that data egress fees were brought up earlier. “In conclusion, AnVILWorkflow proves most advantages for analyzing a bulk of samples on relatively simple workflows”: Is the “most advantages” phrased right? “most advantageous”? Also, the lack of exaggeration when describing the significance of the work is refreshing.\n\nGithub.io documentation\nThe image on the home page does not load. Looks like a broken link. There are some errors that look like they came from chunks with echo = FALSE (e.g. “Error : ‘avworkspace_clone’ failed:” and “Error in mget(arg_names, environment): object ‘billingProjectName’ not found”). Perhaps the Rmd/Qmd needs to be fixed and rerun or make errors not printed? Typically there are installation instruction on the README, especially in combination with a quick start guide. I know there are instructions on Bioconductor, but the first place many people look is the Github repository README, so they should be there too. Consider adding the command to install the development version too using devtools::install_github().\n\nThe source code\nThe code is documented well using roxygen2 and seems tidy Overall The jsonlite package is used for JSON parser, but a much faster package is available called RcppSimdJson. This should be a simple drop in replacement for the most part and will make json parsing 100s of times faster and more RAM efficient. However, this might not matter if only small JSON files are being parsed. There are some dependencies that could be replaced with base R code, which would make maintaining the code easier: dplyr, plyr, stringr, and tidyr. Some of these might not be worth the effort to replace, but stringr for example is only used in one place to convert something to title case. The only non-trivial thing dplyr and plyr are doing are table joins and the merge function can do this in base R. dplyr::filter could easily be replaced with standard R subsetting. I think the tidyverse packages are great for interactive use and data analysis scripts, but not ideal as dependencies since they are large, complex, and frequently break backwards compatibility. However, there is always a balance between dependencies and development time/effort, so this should be considered on a case-by-case basis. Consider adding a LICENSE file to the repository. I know its in the DESCRIPTION file, but that is specific to R, and LICENSE is the standard for most software and then Github will be able to read it and display the license, which is important information for many users.\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? 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/13-1257
|
https://f1000research.com/articles/13-1256/v1
|
21 Oct 24
|
{
"type": "Software Tool Article",
"title": "SCUBA implements a storage format-agnostic API for single-cell data access in R",
"authors": [
"William M. Showers",
"Jairav Desai",
"Krysta L. Engel",
"Clayton Smith",
"Craig T. Jordan",
"Austin E. Gillen",
"William M. Showers",
"Jairav Desai",
"Krysta L. Engel",
"Clayton Smith",
"Craig T. Jordan"
],
"abstract": "While robust tools exist for the analysis of single-cell datasets in both Python and R, interoperability is limited, and analysis tools generally only accept one object class. Considerable programming expertise is required to integrate tools across package ecosystems into a comprehensive analysis, due to their differing languages and internal data structures. This complicates validation of results and leads to inconsistent visualizations between analysis suites. Conversion between object formats is the most common solution, but this is difficult and error-prone due to the rapid pace of development of the analysis suites and their underlying data structures. To address this, we created SCUBA (Single-Cell Unified Backend API), an R package that implements a unified data access API for all common R and Python single-cell object formats. SCUBA extends the data access approach from the widely used Seurat package to SingleCellExperiment and anndata objects. SCUBA also implements new data-specific access functions for all supported object types. Performance scales well across all SCUBA-supported formats. In addition to performance, SCUBA offers several advantages over object conversion for the visualization and further analysis of pre-processed single-cell data. First, SCUBA extracts only data required for the operation at hand, leaving the original object unmodified. This process is simpler, less error prone, and less memory intensive than object conversion, which operates on the entire dataset. Second, code written with SCUBA can use any supported object class as input, with simple and consistent syntax across object formats. This allows a single analysis script or package (like our interactive single-cell browser, scExploreR) to work seamlessly with multiple object types, reducing the complexity of the code and improving both readability and reproducibility. Adoption of SCUBA will ultimately improve collaboration and reproducible research in single-cell analysis by lowering the barriers between package ecosystems.",
"keywords": [
"single-cell sequencing",
"multimodal",
"software tools",
"R package",
"Python",
"visualization"
],
"content": "Introduction\n\nThe rapidly evolving landscape of single-cell sequencing methods has led to the production of increasingly large and diverse single-cell datasets, greatly improving our knowledge of both inter- and intra-patient heterogeneity in a wide range of diseases and normal tissues.1,2 While there are many excellent tools available for analyzing single-cell datasets in both the Python and R ecosystems, interoperability is hindered by the use of incompatible object classes (Figure 1A). Analysis tools generally only accept one object class, forcing users to commit to a suite of packages at the beginning of an analysis. This restriction limits access to tools outside that suite, creating “walled gardens” that pose several challenges for single-cell analysis. Single-cell analysis can be inaccessible to bench scientists due to the programming experience required, and different object formats make it even more difficult for biologists to analyze data. The implementation of popular object formats in both Python and R requires users to be fluent in both programming languages, and it is difficult and time consuming to learn both without formal education in data structures and syntax in each language. The widespread use of multiple object formats also makes it difficult to validate results produced by one analysis suite with another, and visualizations produced with different analysis suites are not consistent. Additionally, the practical analysis of objects with large numbers of cells requires a way to interact with on-disk matrices rather than loading all data in memory. On-disk matrix implementations are analysis suite-specific, which introduces additional barriers to effective analysis. For example, anndata objects are natively stored in the memory-efficient HDF5 format, but anndata objects are not compatible with the Bioconductor’s single-cell tools or Seurat. If a user converts an anndata object to Seurat or SingleCellExperiment format, they must use a different on-disk matrix implementation specific to that format, which further restricts the analyses that can be performed. If single-cell object formats were interoperable, it would be easy for researchers to analyze data from any single-cell dataset, regardless of the object format used when the dataset was generated, but unfortunately this is not the case.\n\nA) Raw single-cell sequencing data is stored in defined object classes, and processed downstream by packages that only accept one object class. This creates “walled garden” analysis suites of incompatible packages that complicate single-cell analysis. When a specific downstream package is desired, the user will need to convert between object formats prior to use. This is possible, but the process is difficult and error-prone. B) SCUBA returns feature expression data, metadata, and reduction coordinates from Seurat, SingleCellExperiment, and Anndata objects in a consistent output format. An overview of each object structure is shown, with rectangles indicating data matrices stored in each object. Dimensions of the matrices are labeled with “cells” or “genes” (features), and matrices placed adjacent to one another indicate requirements that matrices have the same number of values in the dimension indicated (i.e. for Seurat objects, the “reduction coordinates” and “gene expression” matrices must have the same number of cells, but may have varying number of genes (or in the case of reduction coordinates, dimensions). Next to the description of each matrix, object-specific code to retrieve the matrix is given. If additional modalities are supported by an object type, the structure of matrices specific to modalities are shown, along with code to retrieve data on alternate modalities. The output format for SCUBA is shown at the bottom of the panel. The output is a single R data.frame with values for each variable requested for each cell. The S3 methods added by SCUBA to yield the output format are shown in blue, and are based on the existing FetchData generic and method from Seurat.\n\nCurrently, the most effective solution is to manually convert between object classes. All major single-cell analysis packages implement conversion functions, and third-party packages such as sceasy3 are specifically designed for these conversions. However, inconsistencies in approaches to object structure across implementations often result in data loss upon conversion, which is difficult to overcome. Additionally, the rapid development of these packages means that conversion functions are difficult to maintain and frequently break due to changes in other packages. This is especially true when converting to and from the anndata format, since this format is implemented in the Python programming language, and the Seurat and SingleCellExperiment objects are implemented in the R programming language. Even if conversion is successfully achieved without loss of data quality, it has recently been demonstrated that results from Seurat differ from those of Scanpy,4 despite the fact the two packages implement ostensibly identical processing steps. Addressing interoperability and consistency issues between analysis suites is crucial to ensuring the fidelity and reproducibility of single-cell analysis results, making consistent visualizations across suites essential.\n\nRather than conversion between objects, we propose a more sustainable approach to the visualization and further analysis of pre-processed single-cell data by implementing a unified API for all common single-cell object formats. Here, we present Single-Cell Unified Backend API (SCUBA), an R package based on the data accession function in the widely used Seurat5 package that returns data from Seurat, SingleCellExperiment, and annadata objects in a common format for downstream visualization and analysis (Figure 1B). SCUBA also implements new data-specific access functions for all supported object types. Data is returned in a single R data.frame, with requested variables as columns, and cells as rows. The functions in this package allow users to plot data in a consistent manner from these object types in R, without requiring conversion. SCUBA can also be used in functional programming applications as the basis for single-cell plotting packages, or in the development of Shiny apps. For objects with very large numbers of cells, it is now possible to choose the object class based on on-disk storage performance and produce visually consistent plots without having to downsample the object. Packages and scripts created with SCUBA are flexible with regard to input type, greatly improving the consistency of results between objects and increasing accessibility of these analyses for non-programmers.\n\n\nMethods\n\nSCUBA provides a unified framework for data access by leveraging R’s S3 object-oriented programming.6 The workflow for data access in SCUBA is based on Seurat’s FetchData method. We implemented a new generic that uses the Seurat FetchData method for Seurat objects, and novel methods for SingleCellExperiment and anndata objects. The generic was chosen as a basis due to its ease of use, and its implementation in Seurat’s plotting functions, which are widely used.\n\nS3 methods were created in SCUBA to extend the existing FetchData generic to SingleCellExperiment and anndata objects. Access to the anndata objects is accomplished using reticulate7 and performing as many operations in python as possible before returning data to R. The workflow from the existing method for Seurat objects is largely unchanged upon re-implementation for these object formats. We used code from the Seurat package under the terms of the package’s MIT license.\n\nIn addition to replicating the behavior of FetchData in SingleCellExperiment and anndata objects, SCUBA includes S3 generics and methods specific to the retrieval of metadata and reduction coordinates from each object format. These methods offer improvements in performance relative to retrieving the same data via FetchData for large objects.\n\nSCUBA can be installed as an R package via GitHub using the devtools8 R package, and can be used on all common operating systems. To ensure compatibility across operating systems, SCUBA is maintained using Continuous Integration (CI), with Github Actions and the testthat9 R package. The Github Actions workflow performs 100+ tests on recent Linux R and Python versions whenever a pull request is created. Tests are additionally run on Mac OS and Windows for releases. The dataset used for testing is a downsampled version of the acute myeloid leukemia reference dataset10 from Triana et al. 2021.11\n\nIf using SCUBA with Seurat or SingleCellExperiment objects, no further installation is necessary beyond the R dependencies. For anndata objects, the reticulate7 R package and a Python installation are required. The following python packages must be manually installed: pandas,12 numpy,13 scipy,14 and anndata.15 We recommend installing these packages in an anaconda16 environment and loading the environment in R with reticulate::use_condaenv(), but this is not required. Detailed installation instructions are available on the SCUBA GitHub Page.\n\n\nUse cases\n\nThe features of SCUBA fall broadly into three categories; data access, data visualization, and data exploration. The functions provided in these categories can be used independently or in a stepwise pipeline. Generally speaking, SCUBA works best for objects that have been filtered and clustered, though SCUBA can work on objects in any state as long as the data being requested exists. Here we highlight independent use cases using a downsampled version of the acute myeloid leukemia reference dataset10 generated by Triana et al.11 Additional vignettes are provided on the SCUBA GitHub page.\n\nExample usage of SCUBA’s FetchData methods is given Figure 2. The existing Seurat method (first column) is compared to the methods added by SCUBA. There are only minor variations in input syntax across the three supported object types, and the required parameters are few, making the methods easy to use. All data requested is specified using the vars parameter. The methods infer whether the data requested is metadata, reduction coordinates, or feature expression by parsing the character vector passed to this parameter. To retrieve feature expression or reduction coordinates, the user adds a “key” with an underscore giving the name of the reduction, or the modality to pull feature expression data from. If using an object with only one modality, the modality key is not needed, and the key is also not needed to retrieve metadata. Minor variations in the key exist between object types, due to object-specific conventions for naming modalities (which are called “assays” in Seurat objects, and “Experiments” in SingleCellExperiment objects). Variations in the layer parameter are based on variations in conventions for naming layers (in SingleCellExperiment objects, “assays”, and in Seurat v4 and earlier, “slots”). The consistency in parameters between the three object types, and the presence of only minor differences in inputs to each parameter, facilitates the writing of scripts for any object type.\n\nThe existing seurat method (first column), is compared to the methods added by SCUBA for SingleCellExperiment and anndata objects (second and third columns). The methods use consistent syntax across object classes, and involve the use of only a few parameters. Pseudocode is used in the examples. object represents a single-cell object. features represents one or more features, from any modality in the object. metadata represents one or more metadata variables, for example, cell type classifications. reduction_dims represents a set of dimensions in a reduction included with the object, with the number of the dimension separated from the reduction with an underscore. For example, to fetch the first and second dimensions of the UMAP projection, reduction_dims would be c(“UMAP_1”, “UMAP_2”).\n\nThe output of FetchData is identical across the three object classes. The output is an R data.frame with values for each requested feature in vars per cell. Columns represent each feature, and rows represent cells.\n\nSCUBA also includes S3 generics and methods specific to the retrieval of metadata and reduction coordinates, which are faster than retrieving the same data via FetchData for R object types. An overview of the fetch_metadata and fetch_reduction functions is given in Figure 3A. As with FetchData, the output of fetch_metadata and fetch_reduction is an R data.frame with data for the requested metadata variables or reduction coordinates, respectively, as columns, and rows for each cell. Figure 3B compares the usage of fetch_reduction and fetch_metadata between supported object types. We implement these methods in anndata objects for consistency in syntax, but their performance is roughly equivalent to FetchData. The functions are easy to use, and the inputs to each function do not vary based on object type. To set defaults for the reduction and cells parameters of fetch_reduction, SCUBA provides several utility methods. default_reduction will search for UMAP, t-SNE, and PCA reductions, and will return them in that order if they exist. get_all_cells will return the IDs of all cells in the object.\n\nA) Overview of outputs of fetch_metadata, for metadata variables, and fetch_reduction, for reduction coordinates. The output is an R data.frame with the metadata or reduction coordinates as columns, and the cells as rows. B) Comparison of the usage of fetch_metadata and fetch_reduction across each object type. For fetch_metadata, the metadata variable or variables to retrieve (which are represented as metadata in this pseudocode example) are specified via a character vector input to vars. For fetch_reduction, the dimensions to return from the reduction coordinate matrix is passed to dims, and the reduction to pull from is specified via reduction. The cells parameter allows the user to specify which cells to fetch reduction coordinates for. For ease of use and flexibility, there is no difference in inputs between object types; only the object itself varies.\n\nFigure 4A-B compares the performance of fetch_metadata and fetch_reduction with the performance of FetchData to pull one metadata variable, and the first and second dimensions of UMAP coordinates, respectively. Run time was tested for each function on random subsets of varying numbers of cells, with five subsets created for each size. The fetch_metadata and fetch_reduction methods were more performant than FetchData in Seurat and SingleCellExperiment objects for all subsets tested. In anndata objects, the runtime of these functions was comparable to that of FetchData. Performance testing for the FetchData methods added by SCUBA was also performed (Figure 4C). Performance of the method for anndata objects exceeds the performance for the existing Seurat method in most cases, and the performance of the SingleCellExperiement method exceeds performance of the Seurat method for the largest subset tested (500k cells).\n\nFive random subsets of the indicated numbers of cells were created from the Human Brain Atlas object downloaded from CellXGene.21 The subsets were saved in the following object formats: Seurat, via saveRDS(), SingleCellExperiment, via HDF5Array::saveHDF5SummarizedExperiment(), and anndata, via write_h5ad. For all tests, the indicated operations were run on each of the five subsets, and the run time was measured using the tictoc22 package. A) Comparison of FetchData methods vs. fetch_metadata for the retrieval of data for a single metadata variable. In most cases, using fetch_metadata to pull metadata was more performant than using FetchData. B) Comparison of FetchData methods vs. fetch_reduction for the retrieval of data for a pair of reduction coordinates. fetch_reduction was more performant than FetchData for the retrieval of reduction coordinates in most cases. C) Performance of the FetchData methods developed for SingleCellExperiment and anndata objects, compared to the existing FetchData method for Seurat objects. A single feature was pulled via FetchData for each of the random subsets for the indicated object and number of cells.\n\nFigure 5 gives an example usage of SCUBA methods to create plots with consistent visuals across object types. Figure 5A shows the scripts to create a density plot showing expression by cell type from each of the three supported object types, showing regions of the script that vary between object types, and regions that are conserved. Figure 5B shows the output of the example script. The script demonstrates the ease at which expression data can be visualized from each object format, and the ease at which plot visuals can be harmonized across object formats.\n\nA) Example script for visualizing expression of a gene by cluster in a density plot for each of the three supported object types. The three boxes for FetchData indicate slight variations in the script for each object type. All downstream code is the same across object formats. B) Output of the plotting script in (A). Output does not vary by object type.\n\nAny plot visualizing a combination expression data, metadata, and reduction coordinates can be created by generating a table from FetchData, fetch_metadata, or fetch_reduction, and passing the output table to downstream plotting code. Plotting is performed via ggplot217 in this example, but any other plotting package that accepts a data.frame or a tibble as input may be used. If desired, it is also possible to convert to a pandas12 dataframe via Reticulate,7 and perform plotting operations in python. The flexibility of SCUBA’s data access methods facilitate the creation of a broad variety of plots from single-cell data.\n\nFigure 6 shows an example script that simplifies the printing of unique values of a metadata variable represented in an object, which is a commonly used basic operation in analysis. With SCUBA, this operation can simply be performed by calling fetch_metadata on the object and piping the results to unique(). The language used is the same for all supported object classes, which negates the need to memorize and use the most efficient function calls for each respective object type.\n\nThis figure compares the usage of SCUBA with the most efficient equivalent operations for viewing the unique values of a metadata variable represented in an object. The operation with SCUBA is shown in the first column, and the most efficient equivalents are shown in the second column. SCUBA simplifies this operation, allowing for the development of scripts that are generalized for multiple object types.\n\n\nConclusions\n\nSCUBA addresses issues with interoperability between single-cell object formats by providing a flexible backend that returns data in a consistent format, via a consistent interface. The consistent output format of SCUBA facilitates downstream use in functional programming applications (plotting scripts, packages, etc.) and allows for consistent visualizations across object types. Packages and scripts using SCUBA will not require object conversion prior to use, conferring several advantages for end users. Users will not have to risk data loss upon object conversion, and analysis will be more straightforward without conversion, requiring less programming experience. Packages made with SCUBA will also allow users to choose object classes based on storage and performance characteristics that are best for the specific dataset, rather than being constrained to a class based on downstream packages. SCUBA does not allow users to use any analysis package with any object format, however. The aforementioned benefits only apply to packages and scripts created using SCUBA. SCUBA also only performs data access operations, and is not for object assembly, clustering, or filtering. Because of this, SCUBA is not a replacement for analysis packages such as Seurat and Scanpy. Instead, SCUBA allows users to visualize objects that have been prepared with these analysis packages in the same manner, regardless of object class.\n\nSupport for MuData18,19 will be added in the future, as this Python object class is especially useful for storing data from multimodal single-cell sequencing experiments. SCUBA is particularly well suited for interactive use, such as in Shiny apps, where multiple object formats may be used as inputs. We developed a single-cell browser, scExploreR,20 that allows users to create consistent Seurat-style visualizations from either Seurat, SingleCellExperiment, or anndata objects. SCUBA can also be used to create a plotting package that produces visuals from any supported object class for reports and shiny apps, and a QC package reporting the results of preprocessing steps such as filtering, clustering, and batch correction could also be created using SCUBA. The flexibility of SCUBA is envisioned to facilitate analysis and visualization of preprocessed data, unifying disparate object-based package ecosystems.\n\n\nEthics and consent\n\nEthical approval and consent were not required.",
"appendix": "Data and software availability\n\nSCUBA uses two third-party datasets for performance benchmarking, testing, and demonstration in the manuscript. The datasets are described below.\n\nFigshare: Expression of 197 surface markers and 462 mRNAs in 15281 cells from blood and bone marrow from a young healthy donor. https://doi.org/10.6084/m9.figshare.13398065.v4. 10\n\nThis project contains the following underlying data:\n\n• 200AB_projected.rds. (Seurat object with 15821 cells, showing the expression of 197 surface markers and 462 mRNAs in bone marrow from a young healthy donor).\n\nThe dataset is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nCELLxGENE: Human Brain Cell Atlas v1.0. https://cellxgene.cziscience.com/collections/283d65eb-dd53-496d-adb7-7570c7caa443.\n\nThis project contains the following underlying data:\n\n• cc9bfb86-96ed-4ecd-bcc9-464120fc8628.rds. (Seurat object with 800k non-neuronal cells used for performance benchmarking in the manuscript. The file is accessed by selecting “All non-neuronal cells” and then the.rds radio button).\n\nThe dataset is available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nThe Velten et al. dataset 10 was processed to yield a format suitable for testing and demonstration of SCUBA, downsampled, and stored in the inst/extdata/ and data/directories of the SCUBA repo. Scripts used in these operations and performance benchmarking are available at the manuscript GitHub repo: https://github.com/amc-heme/SCUBA_Manuscript. Working examples of code shown in figures 2, 3, 5, and 6 are also stored in this repo.\n\nSoftware, up to date source code, and tutorials are available from: https://github.com/amc-heme/scuba\n\nArchived source code at time of publication: https://zenodo.org/doi/10.5281/zenodo.13776167\n\nLicense: MIT\n\n\nAcknowledgements\n\nThe authors would like to acknowledge Monica Ransom, Sarah E. Staggs, Stephanie R. Gipson, Abbigayl Burtis, and Devin Burke for their thoughtful comments and suggestions during the development of this package and the writing of this manuscript.\n\n\nReferences\n\nSchäfer PSL, Dimitrov D, Villablanca EJ, et al.: Integrating single-cell multi-omics and prior biological knowledge for a functional characterization of the immune system. Nat. Immunol. 2024; 25: 405–417. PubMed Abstract | Publisher Full Text\n\nZeng AGX, et al.: A cellular hierarchy framework for understanding heterogeneity and predicting drug response in acute myeloid leukemia. Nat. Med. 2022; 28: 1212–1223. PubMed Abstract | Publisher Full Text\n\nKiselev V, Huang N: sceasy.2022.\n\nWolf FA, Angerer P, Theis FJ: SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 2018; 19: 15. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHao Y, et al.: Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 2024; 42: 293–304. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWickham H: S3. Advanced R. Chapman and Hall/CRC; 2019. Publisher Full Text\n\nUshey K, Allaire J, Tang Y: reticulate: Interface to ‘Python’.2023.\n\nWickham H, Hester J, Chang W, et al.: devtools: Tools to Make Developing R Packages Easier.2022.\n\nWickham H: testthat: Get Started with Testing. The R Journal. 2011; 3: 5. Publisher Full Text\n\nVelten L, Triana S, Haas S, et al.: Expression of 197 surface markers and 462 mRNAs in 15281 cells from blood and bone marrow from a young healthy donor. [Dataset]. Figshare. 2021. Publisher Full Text\n\nTriana S, et al.: Single-cell proteo-genomic reference maps of the hematopoietic system enable the purification and massive profiling of precisely defined cell states. Nat. Immunol. 2021; 22: 1577–1589. PubMed Abstract | Publisher Full Text | Free Full Text\n\nThe pandas development team: Pandas.2023. Publisher Full Text\n\nHarris CR, et al.: Array programming with NumPy. Nature. 2020; 585: 357–362. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVirtanen P, et al.: Author Correction: SciPy 1.0: fundamental algorithms for scientific computing in Python (Nature Methods, (2020), 10.1038/s41592-019-0686-2). Nat. Methods. 2020; 17: 352–352. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVirshup I, Rybakov S, Theis FJ, et al.: anndata: Annotated data.2021. 2021.12.16.473007. Publisher Full Text\n\nConda contributors: Conda: A system-level, binary package and environment manager running on all major operating systems and platforms.2024.\n\nWickham H: Ggplot2: Elegant Graphics for Data Analysis. Switzerland: Springer; 2016. Publisher Full Text\n\nBredikhin D, Kats I, Stegle O: MUON: multimodal omics analysis framework. Genome Biol. 2022; 23: 42. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVirshup I, et al.: The scverse project provides a computational ecosystem for single-cell omics data analysis. Nat. Biotechnol. 2023; 41: 604–606. PubMed Abstract | Publisher Full Text\n\nShowers W, Desai J, Gipson S, et al.: scExploreR: a Flexible Shiny App for Democratized Analysis of Multimodal single-cell RNA-seq Data.2024.\n\nSiletti K, et al.: Human Brain Cell Atlas v1.0. [Dataset]. CELLxGENE. Reference Source2023.\n\nIzrailev S: tictoc: Functions for Timing R Scripts, as Well as Implementations of ‘Stack’ and ‘StackList’ Structures.2023."
}
|
[
{
"id": "346283",
"date": "17 Dec 2024",
"name": "Huamei Li",
"expertise": [
"Reviewer Expertise Bioinformatics",
"Immunogenetics",
"Single-cell and spatial technologies"
],
"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\nShowers et al. developed the SCUBA R package as a unified API for single-cell data analysis. In single-cell and spatial transcriptomics studies, data format conversion between Seurat, SingleCellExperiment, and AnnData often presents challenges, leading to obstacles in downstream analyses. While several tools have been developed to address data format conversion issues, SCUBA provides a unified and user-friendly interface for handling multiple formats and simplifies single-cell data processing workflows, making it a promising tool for practical applications. However, several concerns regarding SCUBA require further clarification:\n1) The README file available at https://github.com/amc-heme/SCUBA/tree/main does not include examples demonstrating how SCUBA reads Seurat, SingleCellExperiment, and AnnData formats from local files. Additionally, it is unclear whether SCUBA addresses compatibility issues arising from different versions of these formats, such as Seurat 4.0+ versus Seurat 5.0+. Can SCUBA facilitate seamless data format conversion and overcome challenges posed by version discrepancies?\n2) While SCUBA provides application examples for single-cell datasets, it remains unclear whether the tool can be effectively extended to spatial transcriptomics datasets generated by different platforms. Clarification on its applicability to spatial datasets would be beneficial.\n3) To enhance visualization capabilities, it is recommended that SCUBA include optional smoothing methods for displaying the expression distribution of feature genes. This would allow for better identification of regions with concentrated expression of specific features.\n4) The SCUBA documentation could be further improved by providing more detailed explanations of the functions, their usage, and intended purposes. Additionally, including a comprehensive analysis example that integrates both single-cell and spatial transcriptomics data would help illustrate the full workflow and practical utility of SCUBA.\n\nIs the rationale for developing the new software tool clearly explained? Yes\n\nIs the description of the software tool technically sound? Yes\n\nAre sufficient details of the code, methods and analysis (if applicable) provided to allow replication of the software development and its use by others? Partly\n\nIs sufficient information provided to allow interpretation of the expected output datasets and any results generated using the tool? Yes\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": []
},
{
"id": "334007",
"date": "15 Jan 2025",
"name": "Kristian Ullrich",
"expertise": [
"Reviewer Expertise Comparative Genomics",
"Bioinformatics",
"R Programming"
],
"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 provide a valuable R package that implements a unified data access API for single-cell object formats like `anndata` objects (Python) and `Seurat/SingleCellExperiment` objects (R). The SCUBA API (implemented in R) keeps the original single-cell objects unmodified and use three data accession methods, namely `FetchData`, `fetch_metdata` and `fetch_reduction`. To more easily compare pre-processed data stored in common single-cell data formats, like `AnnData`, `SingleCellExperiment` (SCE) and `Seurat`, the authors fetch metadata from cells and genes from the original object and create a `data.frame` R object with the requested features. Using the `data.frame` object, downstream plotting function are provided to create plots in the `ggplot2` R package grammar.\nCode review Given the dependency issues related to R-base version and Python version, I would encourage the authors to submit their package to either CRAN or Bioconductor R repository so that R package community standards are tested in a continious integration setup. The authors should try to alter their code to pass at least the R-CMD-check without warnings and errors.\nIn the \"Use cases\" section, the authors claim that \"Additional vignettes are provided on the SCUBA GitHub page\", which is not true time of writing this review. Please add the mentioned vignettes to the GitHub page.\nThe provided R functions should contain runnable examples. Building a vignette would help the community to present the basic functions from the R package and provide more background information, if needed. I would suggest the authors to include a github workflow to create the R package documentation, vignettes and convert it into a website e.g. with the `pkgdown` package or similar workflow.\nSoftware\nI was able to install the software and run the examples given on the main github page, despite the need to pre-load the `Seurat` R package. As indicated in the Minor comments part, the three functions `reduction_names()`, `assay_names()` and `features_in_assay()` have been removed from the repository and the given example code block should be also removed from the github page. The Rmarkdown files on the github page https://github.com/amc-heme/SCUBA_Manuscript has been inspected and partially run. I have not re-created the subset data sets, however the code base seems to be fine.\nMajor comments\nIf many genes are requested by the `FetchData` function, creating a single `data.frame` has the offsite to not benefit from sparse data structures leading to high memory footprints. Please implement some checks to prevent a user given the local resources to request too many gene features. Please remove \"manually\" from the sentence: \"Currently, the most efective solution is to manually convert between object classes.\" Here, manually implies a programatically high efford to do so, which in my opinion is not true, given the existing converting tools like `SeuratWrapper`, `zellkonverter`, `SCEasy Converter` `scDIOR`. Please add the corresponding literature for the mentioned tools. In your R DESCRIPTION file you set the `reticulate` and `anndata` R packages as suggests, however for your API to be fully functional these packages needs to be imported. Please change accordingly.\nMinor comments\nPlease change the DESCRIPTION and add the corresponding author/creators in the github repository. Please alter the examples from your initial github page so that they work as expected. E.g. the `FetchData` function for Seurat objects is not pre-loaded, one need to first import Seurat `library(Seurat)`. Please remove the following example part from your github pages, sicne the functions have been removed and are not working anymore `reduction_names()`, `assay_names()` and `features_in_assay()`. Please update the corresponding `fetch_...` function main description and param field about what object types are supported, since the `AnnDataR6` class in most cases is supported but not mentioned. Please rephrase \"Single-cell analysis can be inaccessible to bench scientists due to programming experience required, ...\", in my opinion this sentence is formulated too harshly, as it is possible e.g. to convert and analyze single-cell objects with GUI-based solutions such as usegalaxy.eu and the SCEasy Converter plugin. Please provide a working example for a default user without admin priviliges how to setup and use `reticulate` in R for the usecase described here to access an `AnnData` object and how to install the prerequisite Python packages. The authors refer to the main `reticulate` documentation, however, showing a working code snippet example would be beneficial for scientists not fluent in both programming languages. Please remove \"for all three object types\" from Figure 5A \"Common plotting script for all three object types\", since the plotting function applies on the constructed intermediate `data.frame` object. Figure 6, please change the code example to use the R default pipe operator `|>` instead of the `magrittr` pipe operator `%>%` so that one would not need to pre-load the corresponding libraries.\n\nIs the rationale for developing the new software tool clearly explained? Yes\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? 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? Partly",
"responses": []
},
{
"id": "350233",
"date": "29 Jan 2025",
"name": "Damian Panas",
"expertise": [
"Reviewer Expertise Single-cell Genomics",
"Bioinformatics"
],
"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 study, William M. Showers and colleagues developed SCUBA, an R package designed to facilitate the access to single-cell data stored in various formats commonly utilized by single-cell data analysis software in R (Seurat, Scran) or Python (Scanpy). These single-cell data storage formats include SeuratObject (Seurat), SingleCellExperiment (Scran, Bioconductor’s single-cell tools), Anndata (Scanpy). Interoperability between R-based and Python-based tools and data types is a real problem in bioinformatics. Several tools are typically used in this case, such as zellkonverter, anndataR, sceasy, or SeuratDisk. However, these tools rely on data type conversion, which can be computationally expensive. SCUBA implements a unified API for single-cell object formats to efficiently access data for exploratory analysis and visualization. It extracts from storage objects using FetchData methods a table with requested features, metadata, and reduction coordinates for each cell. The manuscript is clearly written, with a logical structure that effectively conveys the study's objective and organized in the following structure: 1) Introduction; 2) Methods including subsection Implementation and Operation; 3) Use cases; and 4) Conclusions. The “Use cases” section involve examples of Scuba usage: 1) application of FetchData function to retrieve features, metadata, and dimensionality reduction coordinates; 2) S3 generics and methods for similar tasks as in (1) including functions fetch_metadata and fetch_reduction; 3) speed tests of the functions for SeuratObjects stored in RDS format, SingleCellExperiment and Anndata in h5 formats; 3) presentation of example scripts for single-cell data exploration and visualization. While the issue of single-cell data interoperability is a well-recognized and pervasive challenge in the field, the manuscript in the current form does not appear to present a significant advancement or novel solution to address this problem comprehensively. It represents rather a set of functions that allows accessing data from various single-cell data objects needed for visualization purposes and should be a part of their scExploreR package rather than the standalone package.\nOther comments:\n1) The authors justify the need for SCUBA development by the fact that conversion between different data storage formats results in data loss upon conversion or this process is error-prone. Additionally, the rapid development of single-cell packages means that conversion functions are difficult to maintain and frequently break due to changes in other packages. I don’t understand why data is lost during conversion or why it is error-prone and how their approach overcome these limitations. For me, Scuba has exactly the same problems. In case of mentioned updates in single-cell third-party software and storage formats, Authors’ SCUBA code will require updates in the same way.\n\n2) Authors should explain how different visualization software like CellxGene and many others retrieve features or cell metadata and benchmark them against SCUBA.\n3) One of the most common features of exploratory analysis is retrieval of feature values such as gene expression or chromatin accessibility from raw count or processed feature matrices. While this function is presented in Figure 2, it is omitted in the performance testing in Figure 4. Why? Can SCUBA extract, for example, gene expression values for a specified gene from huge matrices (500k cells) from SeuratObjects, SingleCellExperiments, Anndata objects in efficient manner? Authors show only retrieval of cell coordinates and cell metadata which are stored in smaller data structures.\n\n4) It is not clear if Authors developed also a new faster version of FetchData for SeuratObject.\n5) The speed tests in Figure 4 are confusing. It’s not clear when Authors use native “FetchData” functions from Seurat/Scanpy and when from SCUBA. For example, Figure 4: fetch_metadata is slower than “FetchData” from Scanpy for anndata?\n6) All the differences in run times in A-C are of the order of 0.5-2 seconds, so negligible for users analyzing the single-cell data.\n7) Authors state: “Analysis tools generally only accept one object class, forcing users to commit to a suite of packages at the beginning of an analysis. This restriction limits access to tools outside that suite, creating “walled gardens” that pose several challenges for single-cell analysis.” How Scuba overcomes this problem?\n8) The package lacks robust and well-organized documentation, such as that provided by the aforementioned zellkoverter, anndataR, or SeuratDisk. The use of the FetchData function is also unclear. The name exceptionally follows the Pascal case naming convention, unlike all other functions which follow the Camel case. If this is done deliberately, e.g., to highlight the use of the Seurat or SeuratObject packages, please consider including a namespace so that the user is aware of the external packages being employed. Alternatively, consider adding the fetch_data function to make the SCUBA package appear more like a closed, independent toolkit.\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? Yes\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? No",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1256
|
https://f1000research.com/articles/12-304/v1
|
20 Mar 23
|
{
"type": "Research Article",
"title": "Influence of leftover antibiotics on self-medication in Saudi Arabia: a cross-sectional study",
"authors": [
"Bader Al-Mehmadi",
"Saad Alsubaie",
"Omar Al-Morikhi",
"Fawaz Alqahtani",
"Waad Almutairi",
"Maryam Al-Mutairi",
"Mohammed Alotaibi",
"Saud Alenazi",
"Khalid Alanazi",
"Saad Alsubaie",
"Omar Al-Morikhi",
"Fawaz Alqahtani",
"Waad Almutairi",
"Maryam Al-Mutairi",
"Mohammed Alotaibi",
"Saud Alenazi",
"Khalid Alanazi"
],
"abstract": "Background: Antimicrobial resistance is increasing at an alarming rate. The use of antibiotics without a prescription by a patient or other family members and their inappropriate storage have caused serious health issues as it would lead to antibiotic resistance and exposure to risk of harmful adverse effects unnecessarily. Exploring causes behind their storage in homes and reuse will help us identify the problem in depth and help in recommending effective solutions. Methods: This is a cross-sectional study. Our target study population was the residents of Saudi Arabia. Data were collected by an online questionnaire and analysed by SPSS. Results: A total of 738 participants answered the online questionnaire, from all ages, genders, nationalities, and different socioeconomic backgrounds residing in different regions across the kingdom of Saudi Arabia. 76.42% knew that an antibiotic is a chemical substance used to treat infections. The participants were questioned about when do they start using antibiotics, to which 95.66% (n=706) responded, after consulting a physician, 3.25% (n=24) said when they felt ill for any reason, and 1.08% (n=8) replied after first attempting herbal medicine. 147 participants admitted that they store excess pills of antibiotics after being prescribed for an infection and re-use them later on for symptoms like sore throat and fever. Conclusions: Although strict measures have been put into effect from the Saudi Ministry of Health to reduce antimicrobial resistance caused by misuse of antibiotics by restricting the dispense of antibiotics from pharmacies without a medical prescription, a large portion of the population regardless of age, level of education, or professional background, have continued to store excess pills of antibiotics after an infection treatment and re-use them once they think they need them for new symptoms. This advises for further revision of the current measures to fill those gaps and reduce this habit.",
"keywords": [
"Leftover antibiotics",
"self-medication",
"antimicrobial resistance"
],
"content": "Introduction\n\nRecently, an alarming issue in human health has come to light: the misuse of unused antibiotics. Antibiotics are potent drugs used to treat bacterial infections, but improper administration or storage can cause bacteria to develop resistance. This is why it is essential to complete the entire course of any prescribed antibiotic. Inadequate use of antibiotics can eventually lead to the development of antibiotic-resistant bacteria, so it is also important to be aware of the risks associated with stockpiling antibiotics.1 The primary risk associated with the misuse of unused antibiotics is the development of drug-resistant bacteria. If bacteria are repeatedly exposed to a particular antibiotic, they will develop resistance over time. In addition, if left untreated, this could lead to additional, more difficult diseases that may also be resistant to other drugs, ultimately leaving the infected significantly worse off than before they took the antibiotics.2\n\nAntibiotic resistance can frequently be traced directly to leftover or unfinished medications that have been hidden in homes or sold illegally online without a valid prescription. To combat this issue, it is crucial that governments around the world implement appropriate regulation systems so that appropriate safety precautions are taken whenever possible.1 In a study on the knowledge, attitude, and practice of antibiotic use and misuse among adults attending Primary Healthcare Centres (PHCs) in Arar, several factors have been proposed to explain the increase in antibiotic resistance, including self-medication, cultural factors, behavioral factors, lack of health education, socioeconomic status, education level, and patients‘/parents' pressure on physicians and pharmacists. In this study, 479 applicants participated, and the knowledge score (62.6±25.6) regarding the safe use of antibiotics was relatively high.3\n\nA similar study involving 141 participants in the city of Buraidah and the use of antibiotics found that 75.2% of the participants believe that antibiotics can be used to treat influenza and the common cold, 46.1% believe it is beneficial for fever, and 22.2% believe it is beneficial for headache. Additionally, 30% of participants believed that antibiotics should be kept at home and used when a family member becomes ill. In addition, 67% of study participants stated that antibiotic resistance is only an issue for those who take it and has no bearing on others.4 A second study conducted in Kuwait with 680 participants revealed that 187 (27.5%) of the study population had taken antibiotics without a doctor's prescription within the past year. The majority of them, 166 (88.8%), were also prescribed antibiotics during this period. Ninety-seven (51.9%) of the self-medicated respondents indicated that they had given an antibiotic to another person without a doctor's prescription. 119 (63.6%) reported using antibiotics that were initially prescribed for an infection that recurred, and 21 (11.2%) for a different type of infection. In Kuwait, 59 (31.6% of respondents who self-medicated) purchased antibiotics directly from private pharmacies. Family members (n=50; 26.7%) and friends (n=7; 3.5%) were also sources of antibiotics.5 A study was conducted to determine the prevalence of antibiotic self-medication in Saudi Arabia. More than one-third of respondents (43.4%) indicated that they sometimes self-medicate with antibiotics. Tonsillitis and pharyngitis (76.7%) are the most frequently reported conditions for which antibiotics were self-prescribed. They also discovered that the most common source of antibiotic self-medication was a previous prescription (36.6%).6 Likewise, a study was conducted to evaluate the knowledge and attitudes of Saudi citizens regarding antibiotic use and self-medication. 63.6% of participants reported purchasing antibiotics from pharmacies without a prescription, and 71.1% reported not finishing the antibiotic course because they felt better. In addition, 44.7% of those who used antibiotics (prescribed or non-prescribed) reported keeping antibiotics from incomplete courses of treatment for future use.7 Another study evaluates the general population's knowledge and attitudes regarding antibiotic use in Jeddah, Saudi Arabia. Almost half of those who used antibiotics did so without a prescription, obtaining them from a retail pharmacy (63.9%), a private clinic (15.3%), or someone else's supply (20%). In addition, they discovered that the majority of antibiotic prescriptions were for fever, pain, and/or inflammation (58.2%), followed by respiratory illnesses (21.2%).8 According to a study conducted in China, 48.1% of participants kept antibiotics at home for their children. Regarding the origins of antibiotics, 63.1% of participants who kept antibiotics at home obtained them through a previous prescription, whereas 35.3% reported purchasing their antibiotics from pharmacies.9 For the factors associated with keeping antibiotics at home, the study found that those with a higher level of education were more likely to do so, while those with a medical background were more likely to do so.9\n\nIn a study conducted in Saudi Arabia measuring the knowledge of health-related students about antibiotics, 50.0% of participants believed antibiotics could be used safely without consulting a physician.10 The majority of participants in the same study believed that antibiotics can be used instead of anti-inflammatory drugs to treat pain and inflammation.10 In the previous study, the majority of participants believed that antibiotics could be used to treat viral infections,10 and a similar study conducted in Qatar found that nearly half of participants believed antibiotics could be used to treat viral illness.11 This study also found that 82% of participants used antibiotics without a prescription, 37% used antibiotics prescribed for another family member, and 27% used antibiotics prescribed to them for a similar condition.11\n\nAccording to research conducted in Saudi Arabia, certain risk factors may be more prevalent in Saudi Arabia than in other countries. As presented by a Riyadh hospital, one of the risk factors is the misuse of antibiotics. Unoptimized antibiotic dosage is another risk factor for the development of bacterial resistance. In addition, one of the most significant risk factors is travel to Saudi Arabia's holy cities, which presents an opportunity for the spread of infectious diseases.12 Another study that examined the use of antibiotics in tertiary hospital settings found that factors such as bed occupancy rate, average length of stay, and number of admissions had no bearing on the development of antimicrobial resistance (AMR), and the same was true for the number of bacteria and percentage of isolates in the group.13 In a study examining participants' knowledge and attitudes regarding antibiotics, it was discovered that between 20 and 50% of the study population shared leftover antibiotics with family members.14 In a separate study, the researchers discovered that a relative's leftover antibiotics, the use of leftover antibiotics from a similar episode of disease, and the presence of a runny nose, sore throat, and fever were all examples of situations in which leftover antibiotics were administered.15\n\nIn 2022, 231 parents participated in a cross-sectional study conducted in six rural primary health centers in Peru to investigate the causes of limited awareness and self-medication of children with antibiotics. The largest knowledge gap was observed among 183 parents (79%) who were unaware that antibiotics are ineffective against viral infections. More than half of the parents (n=120, 52%) admitted giving their children antibiotics without a doctor's prescription.16\n\nFrom September to December of 2018, a cross-sectional survey of medical students from three universities in Colombia was conducted. 532 medical students participated in the study. In the past year, 49.1% of individuals utilized antibiotics. Only 18.2% of those surveyed were familiar with the term “antimicrobial stewardship,” and only 69.3% knew that empiric antibiotic therapy contributes to antibiotic resistance. 11.6% believe that antibiotics should be discontinued as soon as the patient's symptoms improve, while 24.6% believe that prescribing broad-spectrum antibiotics is the most effective way to ensure that the patient is treated. In terms of their actions, 28.5% of respondents are aware that resistance is a multifaceted problem, but they take no action because they believe that individual actions will have little impact.17\n\nSimilarly, another cross-sectional study was conducted to investigate rural population knowledge, attitudes, and practices regarding self-medication in south-western Saudi Arabia in 2019. 58% of the 500 responses were from women, while 42% were from men. Pain (38.1%), influenza (26.3%), cough (24%), and allergies (24%) were treated with self-medication. 85% of patients did not consult a physician, were unaware of medicine information inserts, and did not check the expiration date.18\n\n\nMethods\n\nThe study design was a cross-sectional online survey,22 and was distributed through social media platforms to the residents of Saudi Arabia in different regions. A total of 738 participants were included in the study.\n\nThe study was conducted after the ethical approval was taken. The data collection was started on 29 July 2022 and completed on 31 December 2022.\n\nThe study included participants that were currently residing in Saudi Arabia; male and female both were included, and those who were ≥18 years of age. All others who were not willing to participate, did not give consent or <18 years of age were excluded.\n\nInformed consent was the part of online questionnaire and only participants who were voluntarily willing to participate filled the questionnaire.\n\nAs this electronic survey will be conducted in all regions of Saudi Arabia, a cluster sampling technique was used to collect the data from 738 participants. The minimum required sample size of 700 was calculated using the level of precision formula by placing the following values\n\nA self-prepared questionnaire was used to collect data from the participants. The questionnaire had three sections. Section one contained questions about the demographic data, section two contained questions about the knowledge of antibiotics, and section three contained questions about solutions.\n\nThe data was entered and analyzed using SPSS 26.0 (v.26.0, IBM Corporation, New York, USA) (RRID:SCR_002865). Mean and standard deviation will be given for quantitative variables. Frequencies and percentages were given for qualitative variables. Knowledge scores were calculated by counting the correct answers, which were then converted to percentage to see whether the participants had poor, good or excellent knowledge. Pearson-Chi-Squared/Fisher Exact tests were applied to observe associations between qualitative variables. A p-value of <0.05 will be considered as statistically significant.\n\n\nResults\n\n738 participants of all ages, genders, nationalities, and socioeconomic backgrounds, residing in various regions of the kingdom of Saudi Arabia, responded to the online questionnaire (see Table 1).21 76.42% (n=564) knew what an antibiotic was a chemical substance used to treat infections, 14.09% (n=104) thought it was used to relieve pain, 3.25% (n=24) thought it was used to reduce fever, and 6.23% (n=46) had no idea. When asked when they begin using antibiotics, 95.66% (n=706) of the participants responded, after consulting a physician, 3.25 % (n=24) said when they felt ill for any reason, and 1.08% (n=8) replied after first attempting herbal medicine. When asked for which symptoms people most frequently use antibiotics, the following responses were provided: 38.08% (n=281) reported a sore throat, 32.11 (n=237) a fever, 27.10% (n=200) a cold, and 2.71% (n=20) a cough. 28.32% (n=209) of participants selected allergy as the most common side effect of antibiotics, followed by 21.82% (n=161) who selected stomachache, 7.87% (n=58) who selected rash, and 5.01% (n=37) who selected difficulty breathing. The remaining participants chose multiple adverse effects. When asked to define antibiotic resistance, 68.43% (n=505) of respondents said it is a microorganism's adaptability against antibiotics, 3.6% (n=27) said it is a decrease in antibiotic efficacy due to manufacturing errors, and 27.19% (n=206) said they had no idea.\n\nWhen asked if they take antibiotics when experiencing any new non-specific symptom, the following responses were given by the participants: 46.07% (n=340) strongly disagreed, 29.95% (n=221) disagreed, 12.47% (n=92) were neutral, 7.32% (n=54) agreed, and 4.2% (n=31) strongly agreed. 71.54% (n=528) of the participants strongly agreed, 20% (n=149) agreed, 4.61% (n=34) were neutral, 1.76% (n=13) disagreed, and 1.90% (n=14) strongly disagreed when asked if they only use antibiotics with a prescription. 71.41% (n=527) of participants responded with strong agreement to the question, 21% (n=155) with agreement, 4.61% (n=34) with a neutral response, 2.44% (n=18) with disagreement, and 0.54% (n=4) with strong disagreement. When asked if they stored the antibiotics according to the label's instructions, 91.19% (n=673) said yes, while 8.8% (n=65%) said no.\n\nWhen asked if limiting antibiotic prescriptions was a good idea, 91.33% (674 of 674) of participants agreed, while 8.67% (n=64) disagreed. When asked whether prescribing antibiotics encourages their misuse, 82.79% of the respondents (n=611) said “yes,” while 17.21% said “no.” When asked what they believed could be done to reduce antibiotic resistance, 35.64 % (n=263) said antibiotics should only be taken when prescribed by a doctor, 18.56% (n=137) said living a healthy lifestyle would increase immunity, lower the risk of infection, and reduce the need for antibiotics, and 11.92% (n=88) said antibiotics should only be used in life-threatening situations. Only 20.05% (n=148) of the respondents have participated in an antibiotics campaign, but 88.08% (n=650) believe that antibiotics campaigns can alter community habits.\n\nThere is no correlation between average household income and the storage and reuse of antibiotics (p>0.30). A statistically significant correlation existed between age and the use of unused antibiotics (p=0.0019). The remaining 311 participants did not use any leftover antibiotics: 33 (22.4%) were under 20 years of age, 77 (52.38%) were 20—29 years of age, 18 (12.24%) were 30—40 years of age, and 19 (12.93%) were older than 40 years of age. There was no statistically significant correlation between gender and the use of leftover antibiotics (p>0.05); among the 147 participants who used leftover antibiotics, 79 were male (53.74%) and 68 were female (46.26%). There was a statistically significant correlation between having children and reusing antibiotics; among the 147 participants who reused antibiotics, 30 (20.41%) had children, while 117 (79.59%) did not. There was no statistically significant correlation between the number of children and the use of leftover antibiotics. Eight (26.67%) of the 30 participants who used leftover antibiotics and had one or two children, nine (30%) had three or four children, and 13 (43.33%) had more than four children. There was no statistically significant correlation between the level of education and the use of unused antibiotics. Among the 147 participants who used leftover antibiotics, 102 (69.39%) had a college degree or higher, while 45 (30.61%) did not complete high school. There was no statistically significant correlation between occupation and the use of leftover antibiotics; 45 (30.61%) of the 147 participants who used leftover antibiotics were healthcare workers, while 102 (69.39%) were non-healthcare workers. We also found no statistical significance between chronic illness and knowledge of antibiotics or attitude toward unused antibiotics. Additional answers are depicted in Figure 1.\n\n\nDiscussion\n\nWhen asking what antibiotics are and when they should be used, having 738 participants from all regions of Saudi Arabia helped us gain a deeper understanding of the various backgrounds and educational levels of the participants. Providing an analysis of the impact of media and awareness campaigns, when asked when they typically begin using antibiotics, 95.66% (n=706) of respondents said after consulting with a physician. This majority may indicate a high level of awareness, but it may also indicate that the health ministry is effectively implementing and monitoring the restrictive system. Another study conducted in Saudi Arabia in 2021 revealed that 82% of participants who were able to obtain antibiotics did so without a prescription.10\n\nAnother study conducted in Kuwait with 680 participants revealed that 27.5% of the study population had taken antibiotics without a prescription in the previous year. 97 (51.9%) of the self-medicated respondents reported giving an antibiotic to another individual without a prescription. 119 (63.6%) reported using antibiotics initially prescribed for a recurrent infection, while 21 (11.2%) reported using antibiotics for a different type of infection. Family members (n=50; 26.7%) and friends (n=7; 3.5%) were also sources of antibiotics. In Kuwait, 59 (31.6%) of respondents who self-medicated purchased antibiotics directly from private pharmacies (3). When asked when they first used antibiotics, 95.66% (n=706) of the participants in our study said after consulting a doctor, 3.25% (n=24) when they felt ill for any reason, and 1.08% (n=8) after trying herbal medicine for the first time.1\n\nA study revealed that 81.4% of the respondents believed that antibiotic resistance occurs when the body develops a resistance to antibiotics and ceases to function properly.19 When asked what they believe could be done to decrease antibiotic resistance, 88.08% (n=650) of respondents believe that antibiotics campaigns can alter community habits. Community-wide attitude shifts can be easily implemented with the aid of campaigns, resulting in a decline in antibiotic resistance. There was a statistically significant correlation between participant age and the use of unused antibiotics (p=0.0019). 33 (22.4%) of the 147 participants who used unused antibiotics were younger than 20 years old, 77 (52.38%) were 20—29 years old, 18 (12.24%) were 30—40 years old, and 19 (12.93%) were older than 40 years old. We can attribute the increase in the use of leftover antibiotics in the 20—29 age group to multiple factors, including the high proportion of participants in this age group (51.08%). There were numerous perspectives on antibiotic use (n=377), resulting in unregulated use.\n\nThere was a statistically significant relationship between having children and reusing antibiotics; of the 147 participants who reused antibiotics, 30 (20.41%) had children, while 117 (79.59%) did not. This statistic indicates that participants with children were more hesitant than those not having any, either because they feared the side effects of reusing antibiotics or because they were more cautious when it came to their children. There was no statistically significant correlation between occupation and the use of leftover antibiotics; 45 (30.61%) of the 147 participants who used leftover antibiotics worked in healthcare, while 102 (69.39%) did not. This statistic indicates that although healthcare professionals have greater access to information about antibiotics, they continue to use unused antibiotics, which may contribute to an increase in antimicrobial resistance.\n\nA 2022 cross-sectional study revealed that 79% of 183 parents were unaware that antibiotics are ineffective against viral illnesses.16 76.42% (n=564) of those surveyed in our study were aware that antibiotics are chemical substances used to treat bacterial infections; 14.09% (n=104) believed it was used to relieve pain; 3.25 % (n=24) believed it was used to reduce fever; and 6.23% (n=46) had no idea. A similar study involving 141 participants in the city of Buraidah and the use of antibiotics found that 75.2% of participants believed that antibiotics can be used to treat influenza and the common cold, 46.1% believed that antibiotics are beneficial for fever, and 22.2% believed that antibiotics are beneficial for headache. In addition, 30% of participants believed that antibiotics should be kept at home and administered to sick family members. In addition, 67% of study participants stated that antibiotic resistance is only a concern for those who take it and has no effect on others.15 Antibiotics were used to treat pain (38.3%) and cough (24%) in another cross-sectional study conducted in south-western Saudi Arabia in 2019. According to our study, participants used antibiotics for the following reasons: 38.08% (n=281) reported a sore throat, 32.11 (n=237) reported a fever, 27.10% (n=200) reported a cold, and 2.71 (n=20) reported a cough.\n\nWhen addressing the decision to stop antibiotics once the patient is symptom-free, studies have yielded variable results; however, 71.1% of patients did not complete their antibiotic treatment because they felt better.7 A 2018 survey revealed that 11.6% of respondents believed that antibiotics should be discontinued as soon as symptoms subside. While our research yielded similar results to the first study, with 71.41% (n=527) of respondents stating that they complete the course as instructed; the first study had a larger sample size.18 The presence of expired pharmaceuticals in the home can increase the risk of toxicity, suicide, and accidental poisoning of children,19 whereas the presence of unused antibiotics indicates antibiotic misuse and may increase the likelihood of antibiotic resistance.20\n\nStorage at an improper temperature could have negative consequences. Low-stability medications, such as penicillin and cephalosporin, are easily weakened or rendered ineffective by improper storage temperature conditions. They may hinder the recovery from infections. In our study, 91.19% (n=673) of the participants stored the antibiotics in accordance with the label's instructions, while 8.81% (n=65) did not. Our study demonstrates that participants with a higher level of education keep and utilize unused antibiotics, corroborating a Chinese study which found that individuals with a higher level of education are more likely to keep antibiotics at home. In contrast to their findings, our study reveals that medical personnel were less likely to retain unused antibiotics than non-medical personnel. Among the 147 participants who used leftover antibiotics, 102 (69.39%) had a bachelor's degree or higher and 45 (30.61%) did not. 45 (30.61%) of the 147 participants who used leftover antibiotics were healthcare professionals, while 102 (69.39%) were not.9\n\nIn a study, the prevalence of antibiotic self-medication in Saudi Arabia was determined. Over one-third of respondents, or 43.4% reported that they self-medicate with antibiotics on occasion.6 While our study demonstrates that the majority of participants (71.54%; n = 528) only used antibiotics when prescribed, there were a number of participants who used antibiotics off-label. Tonsillitis and pharyngitis account for 76.7% of all instances of antibiotic self-medication.6 Our study reveals that 38.08 percent (n=281) of individuals who self-medicate with leftover antibiotics do so for sore throat, 32.11% (n=237) for fever, 27.10% (n=200) for the common cold, and 2.71% (n=20) for cough. Another study assessed the knowledge and attitudes of the general population in Jeddah, Saudi Arabia, regarding the use of antibiotics. Nearly half of antibiotic users obtained them without a prescription from a retail pharmacy (63.9%), a private clinic (15.3%), or someone else's supply (20%). This study was published in 2018, prior to the 2019 announcement of penalties for violating Saudi Arabia's restrictive regulations. The regulations, which were announced for the first time in 2015, stipulated that pharmacists who sell antibiotics without a written prescription will be subject to a 100,000 SAR fine, license revocation, or six months in jail. In addition, they discovered that fever, pain, or inflammation were the most common reasons for taking antibiotics (58.2%), followed by respiratory illnesses (21.2%).8 In a study conducted in Saudi Arabia to evaluate the knowledge of health science students regarding antibiotics, 50% of participants believed antibiotics could be used without consulting a doctor (8). 71.54% (n=528) of the participants in our study believed antibiotics should only be used when prescribed, with 48% (n=204) of these respondents being healthcare professionals.\n\n\nConclusions\n\nWhile it is understandable that people may believe storing unused antibiotics will be useful in the event of an emergency, there are numerous risks associated with doing so. Although the Saudi Ministry of Health has implemented stringent measures to reduce antimicrobial resistance caused by antibiotic misuse by restricting the dispensing of antibiotics from pharmacies without a prescription, a sizeable proportion (20%) of our sample participants, regardless of age, level of education, or profession, have continued to store excess antibiotic pills after an infection treatment and re-use them. This calls for further revision of the current measures to fill those gaps and reduce this practice, such as selling/distributing the exact number of pills required to treat the current infection per prescription and increasing awareness of the consequences of using antibiotics excessively without consulting a doctor. This may also have an economic benefit, as more antibiotic pills will be available for additional prescriptions.\n\n\nEthical considerations\n\nEthical approval was received from the institutional review board of The Majmaah University for research committee (MUREC) (HA-01-R-088) with the ethical number MUREC-f uly.28/COM-2022/1O-2. Information from the questionnaire will be kept confidential and only used for statistical purposes.",
"appendix": "Data availability\n\nDue to confidentiality of our participants and our university ethical consideration, our data cannot be shared widely/openly. The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request after an Ethical Committee approval (Name: Bader Almehmadi, Assistant professor of medicine, rheumatology consultant; email: b.almehmadi@mu.edu.sa; Article type Research article). The access to the data can be shared/granted for research process only and after the approval involving ethics committee and corresponding author.\n\nFigshare: Influence of leftover antibiotics on self-medication in Saudi Arabia أثر بقايا المضادات الحيوية في المنازل على سلوك المعالجة الذاتية في المملكة العربية السعودية .pdf. https://doi.org/10.6084/m9.figshare.22001894.v1 21\n\nThis project contains the following extended data:\n\n• Influence of leftover antibiotics on self-medication in Saudi Arabia أثر بقايا المضادات الحيوية في المنازل على سلوك المعالجة الذاتية في المملكة العربية السعودية .pdf (Questionnaire).\n\nFigshare: STROBE checklist for ‘Influence of leftover antibiotics on self-medication in Saudi Arabia: a cross-sectional study’. https://doi.org/10.6084/m9.figshare.22001603.v1. 22\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAwadh AM, Raja AK, Mahdi AI: Assessment of knowledge, attitude and practice regarding antibiotics misuse among the public in Saudi Arabia. Egypt. J. Hosp. Med. 2017; 69(5): 2405–2411. Publisher Full Text\n\nYosra A-AS, Al-Hindi.: Investigating the appropriateness of antibiotic usage and misuse for uncomplicated urinary tract infections (UTIs) in the clinics at King Abdul-Aziz Hospital (KAH) in Makkah, Kingdom of Saudi Arabia. Med. Sci. 2020; 24(105): 3485–3493.\n\nAlanazi AM, Alenezi FSG, Alanazi TDM, et al.: Knowledge, attitude and practice of antibiotic use and misuse among adults attending Primary health care in Arar city, Saudi Arabia. Arabia. 2021; 25(111): 1173–1182.\n\nAlhomaidan HT, Shariq A, Almoziraei AM, et al.: Use of Antibiotics among general population of Buraidah, the capital of Qassim Region of Saudi Arabia: A cross-sectional study. Int. J. Med. Dev. Ctries. 2021; 5: 663–668. Publisher Full Text\n\nAwad AI, Aboud EA: Knowledge, attitude and practice towards antibiotic use among the public in Kuwait. PLoS One. 2015; 10(2): e0117910. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlghadeer S, Aljuaydi K, Babelghaith S, et al.: Self-medication with antibiotics in Saudi Arabia. Saudi Pharm. J. 2018; 26(5): 719–724. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEl Zowalaty ME, Belkina T, Bahashwan SA, et al.: Knowledge, awareness, and attitudes toward antibiotic use and antimicrobial resistance among Saudi population. Int. J. Clin. Pharm. 2016; 38(5): 1261–1268. PubMed Abstract | Publisher Full Text\n\nZaidi SF, Baroom MW, Ibrahim Hanbashi A, et al.: Cross-sectional survey among general population regarding knowledge and attitude toward antibiotic usage in Western Saudi Arabia. Pharmacy. 2021; 9(2): 98. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSun C, Hu YJ, Wang X, et al.: Influence of leftover antibiotics on self-medication with antibiotics for children: a cross-sectional study from three Chinese provinces. BMJ Open. 2019; 9(12): e033679. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkbar Z, Alquwez N, Alsolais A, et al.: Knowledge about antibiotics and antibiotic resistance among health-related students in a Saudi University. J. Infect. Dev. Ctries. 2021; 15(07): 925–933. Publisher Full Text\n\nAljayyousi GF, Abdel-Rahman ME, El-Heneidy A, et al.: Public practices on antibiotic use: A cross-sectional study among Qatar University students and their family members. PLoS One. 2019; 14(11): e0225499. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZowawi HM: Antimicrobial resistance in Saudi Arabia: An urgent call for an immediate action. Saudi Med. J. 2016; 37(9): 935–940. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAldawsari A, Tawfik K, Al-Zaagi I Sr: Antimicrobial-Resistant Bacteria and Prescription of Antibiotics at a Tertiary Care Hospital in Riyadh, Saudi Arabia. Cureus. 2020; 12(12). Publisher Full Text\n\nAziz S, Kamel F: Knowledge, attitude and practice toward the use of antibiotics without prescription in Jeddah, Saudi Arabia: a cross-sectional study. J. Med. Sci. 2019; 19(1): 45–50.\n\nAlnasser AHA, Al-Tawfiq JA, Ahmed HAA, et al.: Public knowledge, attitude and practice towards antibiotics use and antimicrobial resistance in Saudi Arabia: A web-based cross-sectional survey. J. Public Health Res. 2021; 10(4): jphr.2021.2276. Publisher Full Text\n\nParedes JL, Navarro R, Watanabe T, et al.: Knowledge, attitudes and practices of parents towards antibiotic use in rural communities in Peru: a cross-sectional multicentre study. BMC Public Health. 2022; 22(1): 1–9. Publisher Full Text\n\nHiguita-Gutiérrez LF, Roncancio Villamil GE, Jiménez Quiceno JN: Knowledge, attitude, and practice regarding antibiotic use and resistance among medical students in Colombia: a cross-sectional descriptive study. BMC Public Health. 2020; 20(1): 1–12. Publisher Full Text\n\nMakeen HA, Albarraq AA, Banji OJ, et al.: Knowledge, attitudes, and practices toward self-medication in a rural population in South-Western Saudi Arabia. Saudi Journal for Health Sciences. 2019; 8(1): 54. Publisher Full Text\n\nEltom EH, Alanazi AL, Alenezi JF, et al.: Self-medication with antibiotics and awareness of antibiotic resistance among population in Arar city, Saudi Arabia. J. Infect. Dev. Ctries. 2022; 16(11): 1762–1767. PubMed Abstract | Publisher Full Text\n\nAl-Shareef F, El-Asrar SA, Al-Bakr L, et al.: Investigating the disposal of expired and unused medication in Riyadh, Saudi Arabia: a cross-sectional study. Int. J. Clin. Pharm. 2016; 38(4): 822–828. PubMed Abstract | Publisher Full Text\n\nAlmehmadi B: Influence of leftover antibiotics on self-medication in Saudi Arabia أثر بقايا المضادات الحيوية في المنازل على سلوك المعالجة الذاتية في المملكة العربية السعودية.pdf. figshare. [Dataset]. Journal contribution. 2023. Publisher Full Text\n\nAlmehmadi B: STROBE checklist for ‘[Influence of leftover antibiotics on self-medication in Saudi Arabia: a cross-sectional study]. figshare. [Dataset]. Online resource. 2023. Publisher Full Text"
}
|
[
{
"id": "205470",
"date": "29 Sep 2023",
"name": "Juan Manuel Vazquez-Lago",
"expertise": [
"Reviewer Expertise Antibiotics"
],
"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 very much for allowing me to review this work. It is an interesting work, focused on a major public health problem, the use of antibiotics. However, the article, from my point of view, needs improvement to be published in this journal.\nFormal aspects: The text does not present line numbering, which makes it difficult to prepare a review report.\nAbstract:\nMethods: The methods reflected in the abstract are scarce. Is the questionnaire used a validated questionnaire?\n\nResults: Part of the results are methodology. \"from all ages...of Saudi Arabia\", since they are inclusion criteria (they do not contribute anything to the results section. The response rate to the questionnaire, the distribution of the sample in terms of sex and age (mean and SD). Where \"147 participants...\" is reported, it does not provide much information to the results (a relative value is better).\n\nConclusions: The conclusions expressed in the abstract are not supported by the results. It must be rewritten.\nIntroduction:\nIt must be reduced. It is difficult to read. The introduction should be structured in 3 paragraphs: (1) describe the topic within which the text is framed; (2) report the gap or lack of knowledge that the text attempts to resolve; (3) propose the questions or objectives that guide the text\nMethodology: this section is very brief. It should be improved.\nThe questionnaire is not provided. It should be contributed to be able to value it. Has this questionnaire been validated on the target population? If not validated, all results are largely compromised. This possible weakness should also be discussed.\n\nHas the questionnaire only been distributed through social networks? People who do not use social networks did not have the opportunity to complete the questionnaire? This is a very important selection bias, as well as an information bias, since access to social networks can be influenced, for example, by social class, educational level, etc., sex...\n\nIt is not necessary to include the sample size calculation formula in the text.\nResults:\nIt should be stated how many were sent the questionnaire and how many of them responded. At no time is the response rate reported.\n\nThe distribution by sex and age must always be reported in the text.\nDiscussion:\nPoorly structured. It should be reviewed.\n\nIn the first paragraph the most notable result of the investigation should always be reported. What does this research contribute new to the scientific world?\n\nThere are no references, or at least I have not been able to objectify them, to the limitations and strengths of the design.\n\nYou can discuss the results obtained with other recently published articles, in order to increase the external validity of your work. (Antibiotics (Basel). 2023 Mar 11;12(3):558. doi: 10.3390/antibiotics12030558.) (Antibiotics (Basel). 2023 Feb 24;12(3):457. doi: 10.3390/antibiotics12030457.)\nConclusions:\nThe paragraph that refers to the conclusions is more a part of the discussion. Conclusions should be written in 2-3 short sentences strongly supported by the results.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? No\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": []
},
{
"id": "209852",
"date": "27 Nov 2023",
"name": "Mohamad Al-Tannir",
"expertise": [
"Reviewer Expertise Public health",
"multidisciplinary clinical research and clinical trials."
],
"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 and objective do not perfectly align.\n\nThe Introduction is written as a literature review of a proposal rather than an introduction of a manuscript.\n\nMethods section lacks important information about the questionnaire and its validity, and the sample size seems underestimated. IRB name and Log should be provided.\n\nResults section is written inappropriately.\n\nDiscussion section should follow the rule of 7 paragraphs of a discussion of a scientific manuscript.\n\nEnglish proofreading is a must.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? No\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? No",
"responses": [
{
"c_id": "12575",
"date": "18 Oct 2024",
"name": "Bader Almehmadi",
"role": "Author Response",
"response": "Title and objective do not perfectly align. response: changes have been made The Introduction is written as a literature review of a proposal rather than an introduction of a manuscript. response: Introduction has been thoroughly edited as per the reviewer suggestions Methods section lacks important information about the questionnaire and its validity, and the sample size seems underestimated. IRB name and Log should be provided. response: changes have been made. IRB details and log is provided in the end of study. Results section is written inappropriately. response: changes have been made Discussion section should follow the rule of 7 paragraphs of a discussion of a scientific manuscript. response: changes have been made English proofreading is a must. response: changes have been made"
}
]
},
{
"id": "219360",
"date": "28 Nov 2023",
"name": "Vitus Silago",
"expertise": [
"Reviewer Expertise Antimicrobial Resistance and Molecular Epidemiology of Infectious 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\nAbstract The conclusion does not reflect what the authors investigated, for instance, the authors investigated individual behavior on how they use antibiotics they were prescribed and not that dispensers at community pharmacies are dispensing without prescriptions. I recommend rephrasing this section to reflect what was done and recommend based on specific findings. The interesting finding is people are not completing their doses, they are misusing antibiotics (one among main drivers of antimicrobial resistance). Therefore, authors may recommend something on proper antibiotics use at community levels.\nIntroduction The first paragraph: …..the misuse of unused antibiotics…., what did Authors mean by “unused” antibiotics? If they meant for “left-over” antibiotics then the term (unused antibiotics) is not proper and if the term (unused) antibiotics are not for “left-over” it is important that the Authors define what they mean by “unused antibiotics” “Left-over” antibiotic indicates that an individual did not complete the full course and the next individual, who may be the same or different person to use the “left-over” antibiotic, will not complete the full course as well. Therefore, from this general knowledge, Authors should add one or two sentences explaining how bacteria develops (or acquires) resistance from incomplete course or left-over I suggest that Authors shorten the Introduction section particularly by referring few and up-to-date studies on “left-over” and “self-medication” The last paragraph of Introduction section should cover gap, problem statement and main objective of the study.\nMethods What social media were used to distribute online questionnaires? How many questionnaires were returned and how many passed to final data analysis after quality check? What were the reasons (e.g., incompleteness, age limits, e.t.c) for dropping out some responses/questionnaires? The last sentence of “Target population” section is not important, it can be deleted “Patient consent” and “Instrument of data collection” section may be merged together because they present more similar information\nResults Authors should avoid starting a sentence with numerals When asked when they begin using antibiotics, ……95.66% (n=706) of the participants responded, after consulting a physician, 3.25 % (n=24) said when they felt ill for any reason, and 1.08% (n=8) replied after first attempting herbal medicine. This sentence is not clear, those 3.25% and 1.08% practiced self-medication with reasons of onset of illness and after failed herbal treatment? Refer to this sentence “71.41% (n=527) of participants responded with strong agreement to the question, 21% (n=155) with agreement, 4.61% (n=34) with a neutral response, 2.44% (n=18) with disagreement, and 0.54% (n=4) with strong disagreement”, which question did Authors referred to? Paragraph 4 (last paragraph of Results section): it is important to perform sub-analysis (if data is available) on the proportion of participants with left-over antibiotics at their homes. This will highlight on the burden of incomplete antibiotic use (and most important the risk of using left-overs) among studied population before reporting factors driving for incomplete antibiotic use\nDiscussion First paragraph, last sentence: a study from 2021 is contradicting with the findings of the current study and Authors should clearly state this. The previous study shows that 82% of participants obtained antibiotics without prescriptions indicating poor practice among community dispensers (most likely) while the current study shows that 95.66% of respondents obtained antibiotics after medical consultation hence with prescriptions. What could be the possible reason(s) if any for this significant change? Second paragraph, second sentence: Authors wrote that, “97 (51.9%) of the self-medicated respondents reported giving an antibiotic to another individual without a prescription”. For my opinion, if an individual self-medicate him/herself, use incomplete course, and then hand-over the left-over antibiotic to the next person it is obvious that no prescription will be required or provided. Therefore, it is not important to end the sentence with “without a prescription”. General comment on Discussion section: Authors kept on repeating their results instead of discussing them.\nConclusion It should be revised. For example, measures implemented by the Ministry of Health (Saudi Arabia) notably limiting community access to antibiotics from community pharmacies without prescription has nothing to do with people’s behavior of using incomplete antibiotic use and storing them for future use. Moreover, it should be noted that it is not “excess” antibiotics (excess sounds like they were prescribed extra antibiotics from actual course they were supposed to be prescribed), this needs correction.\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": [
{
"c_id": "12576",
"date": "09 Oct 2024",
"name": "Bader Almehmadi",
"role": "Author Response",
"response": "Dear Reviewer, Thank you for the suggestion, changes have been done accordingly throughout the manuscript."
}
]
}
] | 1
|
https://f1000research.com/articles/12-304
|
https://f1000research.com/articles/13-1244/v1
|
17 Oct 24
|
{
"type": "Study Protocol",
"title": "Carbapenem-resistant Enterobacterales/Enterobacteriaceae (CRE) in Indonesia: protocol for systematic review and meta-analysis",
"authors": [
"Ika N. Kadariswantiningsih",
"Maulana A. Empitu",
"Bulat Idrisov",
"Derren David Christian Homenta Rampengan",
"Roy Novri Ramadhan",
"Maulana A. Empitu",
"Bulat Idrisov",
"Derren David Christian Homenta Rampengan",
"Roy Novri Ramadhan"
],
"abstract": "Abstract\nBackground Carbapenem-resistant Enterobacterales (CRE) pose a significant global health threat, with increasing prevalence worldwide, including in Indonesia. Despite the public health impact, comprehensive data on the burden of CRE in Indonesia remains fragmented. This protocol outlines a systematic review and meta-analysis aiming to estimate the prevalence of CRE in Indonesia, summarize trends over time, and identify key resistance mechanisms.\n\nMethods We will conduct a systematic search across multiple electronic databases, including PubMed, Scopus, and local Indonesian databases, for studies reporting the prevalence of CRE in Indonesia from 2008 to 2024. Eligibility criteria include observational studies (cross-sectional, cohort, and case-control) and surveillance reports. Data extraction will focus on CRE prevalence, bacterial species, sample types, resistance mechanisms, and study settings (hospital vs. community). Quality assessment of studies will be performed using the Newcastle-Ottawa Scale (NOS). Meta-analysis will be conducted using a random-effects model to estimate pooled prevalence, and subgroup analysis will explore variations by geographical region, period, and healthcare setting.\n\nDiscussion This systematic review and meta-analysis will provide the first comprehensive overview of CRE prevalence in Indonesia, contributing to an improved understanding of the national burden and resistance patterns. The findings will guide public health policies and inform antimicrobial stewardship efforts in Indonesia.\n\nRegistration PROSPERO CRD42024580177",
"keywords": [
"Carbapenem-resistant Enterobacterales",
"CRE",
"antimicrobial resistance",
"prevalence",
"Indonesia",
"infectious disease"
],
"content": "Introduction\n\nThe emergence of carbapenem-resistant Enterobacterales (CRE) is a global health challenge, with Southeast Asia experiencing particularly high prevalence rates of these multidrug-resistant organisms. The widespread dissemination of carbapenemase-producing Enterobacteriaceae (CPE) has been well documented, driven by both clonal expansion and horizontal gene transfer.1,2 Within Southeast Asia, including Indonesia, carbapenem resistance rates are among the highest globally, with some healthcare settings reporting resistance rates exceeding 30%.3,4 This trend underscores the urgency of implementing targeted interventions to curtail the spread of CRE.\n\nCarbapenem resistance in Enterobacterales is mediated through complex mechanisms. The primary mechanism is the production of various carbapenemases such as Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), and oxacillinase-48 (OXA-48).5,6 These enzymes degrade carbapenems, rendering them ineffective against infections once treatable with these last-resort antibiotics. Furthermore, resistance is compounded by additional factors such as efflux pumps and modifications to porin channels, further complicating therapeutic options.7,8 A comprehensive understanding of these mechanisms is essential to developing effective surveillance and intervention strategies for CRE control in Indonesia.\n\nIn Indonesia, studies suggest that the prevalence of CRE varies across different regions. The variation is influenced by factors like antibiotic usage patterns, healthcare practices, and the presence of specific resistance genes.9,10 This systematic review and meta-analysis will critically assess the prevalence and mechanisms of CRE resistance in Indonesia, contributing to the global effort to combat this escalating health crisis. The findings aim to inform healthcare policy and improve the management of CRE infections both within Indonesia and on a broader scale.\n\n\nProtocol\n\nThis review seeks to answer the following question: What is the prevalence, antimicrobial resistance patterns, and clinical outcomes of Carbapenem-resistant Enterobacterales/Enterobacteriaceae (CRE) infections in Indonesia?\n\nThis systematic review and meta-analysis are designed to estimate the pooled prevalence of Carbapenem-resistant Enterobacterales (CRE) in Indonesia from 2004 to 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines.11 The PRISMA-P Checklist is detailed in the Extended data. The review will systematically identify and analyze published studies to provide a comprehensive assessment of CRE prevalence, trends, and resistance mechanisms across different settings in Indonesia. The review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42024580177.\n\nAn exhaustive database search was conducted to gather all pertinent articles on Carbapenem-resistant Enterobacterales (CRE) in Indonesia, covering the period from January 1, 2004, to the start of this study. Publications in both English and Indonesian were sought in databases including PubMed, Google Scholar, Scopus, and Southeast Asian Index Medicus between January 1, 2004 and the start of this study, 2024. Additionally, a manual search using Google was performed to screen the references of identified articles, ensuring comprehensiveness and the inclusion of potentially missed studies.\n\nThe search strategy was developed using the CoCoPop (Condition, Context, Population) framework to structure the search questions and terms. The search terms included: (“Carbapenem-resistant Enterobacterales”), (CRE), (“prevalence”), and (“Indonesia”). These terms were combined using Boolean operators “OR” and “AND” to optimize and refine the search, ensuring the retrieval of all relevant articles. The search strategy is detailed in Appendix 1 (Extended data), and the flowchart of this systematic review is depicted in Appendix 2 (Extended data).\n\nThis review includes studies involving patients or clinical isolates from all age groups (neonates, children, adults) that have been tested for Carbapenem-resistant Enterobacterales (CRE) in both community-acquired and hospital-acquired (nosocomial) infections. Only studies conducted in Indonesia will be included to ensure accurate representation of local epidemiology and CRE burden. The eligible study designs include observational studies (cohort, cross-sectional, case-control) and clinical trials that report on the prevalence, resistance patterns, clinical outcomes, or any measure of disease burden related to CRE. Both published and grey literature (e.g., theses, dissertations, conference proceedings) in English and Indonesian will be considered. Studies must report specific outcomes, such as prevalence rates, antimicrobial resistance profiles, morbidity, mortality, or length of hospital stay associated with CRE infections.\n\nExclusion criteria include studies conducted outside of Indonesia or those that do not provide relevant data to the Indonesian context. Review articles, meta-analyses, systematic reviews, editorials, and opinion pieces are excluded. Additionally, studies focusing on non-human subjects, including veterinary medicine, agriculture (e.g., livestock, aquaculture), or environmental sampling (e.g., water, soil) are excluded unless directly related to human health outcomes. Studies that fail to report specific data on CRE are also excluded, as well as case reports and case series due to potential bias and challenges in generalizing findings from individual cases or small samples.\n\nA structured data extraction approach will be employed for this systematic review and meta-analysis. Initially, two authors will independently screen studies based on their titles and abstracts. Subsequently, full-text articles will be thoroughly reviewed using the predetermined inclusion and exclusion criteria to identify relevant data. A predefined data extraction sheet will be used to systematically record all relevant details from selected studies. Key information to be extracted includes authors, publication year, title, study name, the year the study was conducted, study site (city, province, region), study design, study setting (hospital, community), population (age group), sampling site, comorbidities, CRE detection method, total sample/total isolates, CRE prevalence, upper-lower confidence intervals (CI), CRE prevalence from specific pathogens (e.g., Escherichia coli and Klebsiella pneumoniae), and clinical outcomes other than prevalence (e.g., mortality, survival). Data extraction will be conducted by two authors, and a third author will cross-verify the retrieved data during the analysis phase to ensure accuracy and consistency.\n\nThe quality of the included studies will be assessed by two authors using a modified version of the Newcastle-Ottawa Scale (NOS) for observational studies. Studies receiving 0-3 stars will be considered poor quality, those with 4-5 stars acceptable, and those with 6-9 stars high quality. In cases of disagreement between the reviewers, consensus will be reached through discussion.\n\nThe primary outcome of this systematic review and meta-analysis is to determine the pooled prevalence of CRE in Indonesia. Secondary outcomes include the pooled prevalence of CRE by region, the prevalence in adults versus children, and the prevalence in hospital versus community settings. The review will also examine the prevalence of the most common CRE pathogens.\n\nA random effects model will be applied to estimate the pooled prevalence and antimicrobial resistance patterns of CRE. Subgroup and meta-regression analyses will be conducted to explore potential sources of heterogeneity. Heterogeneity between studies will be quantified using Cochran’s Q test and I2 statistics, with a p-value of <0.05 indicating significant heterogeneity. The Der Simonian-Laird random effects model will account for this variability. Meta-Essentials, a tool compatible with Microsoft Excel, will be used for analysis. Subgroup analyses will focus on region, age group, hospital versus community settings, and specific pathogens. Results will be presented in tabular form and forest plots, and publication bias will be assessed using funnel plot symmetry.\n\nUpon completion, the systematic review will be sent for publication in a peer-reviewed journal.\n\nThis study has not been started yet.\n\n\nDiscussion\n\nThis systematic review and meta-analysis aim to provide a comprehensive overview of Carbapenem-resistant Enterobacterales (CRE) in Indonesia. The findings are expected to shed light on the growing prevalence of CRE, particularly in hospital settings, which mirrors global trends in antimicrobial resistance. This study’s results will be pivotal for shaping infection control policies and antimicrobial stewardship programs within Indonesia’s healthcare system, highlighting the need for enhanced surveillance and targeted interventions.\n\nRegional variations in CRE prevalence are likely to emerge, influenced by disparities in healthcare infrastructure, antimicrobial usage, and infection control practices. These variations may underscore the need for localized strategies in regions with a higher burden of CRE. Additionally, the study will assess the prevalence across different population groups and between hospital and community settings, which could reveal the spread of CRE beyond healthcare facilities, complicating containment efforts and necessitating broader public health interventions.\n\nWhile this review offers critical insights, it may face challenges such as heterogeneity in study designs, diagnostic methods, and the potential for publication bias. Subgroup and meta-regression analyses will be employed to address these limitations, but caution is warranted when interpreting the pooled data. Nevertheless, this analysis will provide crucial information for guiding national policies on antimicrobial resistance and informing future research and interventions to mitigate the threat posed by CRE in Indonesia.\n\n\nEthical considerations\n\nThis systematic review is based on the analysis of published articles (secondary data) and does not require approval by an ethics committee.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare: Extended dataset for: “Carbapenem-resistant Enterobacterales/Enterobacteriaceae (CRE) in Indonesia: protocol for systematic review and meta-analysis.”, https://doi.org/10.6084/m9.figshare.27134661.v5. 12\n\nThis project contains the following extended data:\n\n1. Appendix 1. Search strategy for Pubmed\n\n2. Appendix 2. PRISMA Flowchart\n\n3. PRISMA-P checklist\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: PRISMA-P checklist for ‘Carbapenem-resistant Enterobacterales/Enterobacteriaceae (CRE) in Indonesia: protocol for systematic review and meta-analysis’, https://doi.org/10.6084/m9.figshare.27134661.v5. 12\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nLogan LK, Weinstein RA: The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. J. Infect. Dis. 2017; 215(suppl_1): S28–S36. PubMed Abstract | Publisher Full Text | Free Full Text\n\nDuin D v, Doi Y: The Global Epidemiology of Carbapenemase-Producing Enterobacteriaceae. Virulence. 2016; 8(4): 460–469.\n\nHsu LY, Apisarnthanarak A, Khan E, et al.: Carbapenem-Resistant Acinetobacter Baumannii and Enterobacteriaceae in South and Southeast Asia. Clin. Microbiol. Rev. 2017; 30(1): 1–22. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPotter RF, D’Souza AW, Dantas G: The Rapid Spread of Carbapenem-Resistant Enterobacteriaceae. Drug Resist. Updat. 2016; 29: 30–46. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMekonnen Y: Fecal Carriage of Carbapenem Resistant Enterobacterales and Associated Factors Among Admitted Patients in Saint Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia. Infect. Drug Resist. 2023; 16: 6345–6355. PubMed Abstract | Publisher Full Text | Free Full Text\n\nIovleva A, Doi Y: Carbapenem-Resistant Enterobacteriaceae. Clin. Lab. Med. 2017; 37(2): 303–315. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJaggi N, Chatterjee N, Singh V, et al.: Carbapenem Resistance in Escherichia Coli and Klebsiella Pneumoniae Among Indian and International Patients in North India. Acta Microbiol. Immunol. Hung. 2019; 66(3): 367–376. PubMed Abstract | Publisher Full Text\n\nPaveenkittiporn W, Lyman M, Biedron C, et al.: Molecular Epidemiology of Carbapenem-Resistant Enterobacterales in Thailand, 2016–2018. Antimicrob Resist. Infect. Control. 2021; 10(1). Publisher Full Text\n\nMusa AY: Detection of Carbapenem Resistance Among Enterobacteriaceae Pathogens Isolated From Clinical Samples in Shendi Locality. Middle East Res. J. Microbiol. Biotechnol. 2023; 3(02): 43–47. Publisher Full Text\n\nAli SY, Malik T: Detection of Carbapenem Resistant Klebsiella Species Isolated From Clinical Samples. Pure Appl. Biol. 2020; 9(2). Publisher Full Text\n\nSarkis-Onofre R, Catalá-López F, Aromataris E, et al.: How to properly use the PRISMA Statement. Syst. Rev. 2021; 10: 1–3.\n\nKadariswantiningsih IN, Empitu MA: Extended Dataset for “Carbapenem-resistant Enterobacterales/Enterobacteriaceae (CRE) in Indonesia: protocol for systematic review and meta-analysis”. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "354977",
"date": "28 Jan 2025",
"name": "Oznur Caliskan-Aydogan",
"expertise": [
"Reviewer Expertise Microbiology and nanotechnology"
],
"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 Methods and protocol of this manuscript is detailly documented well. However, Introduction and discussion should be extended. Conclusion and future perspectives should be included. The details and data about the mentioned reviewed papers for this manuscript have not been summarized. This manuscript need to be improved and enriched with the more literature resources and their findings.\n\nSpecific comments Carbapenem-resistant Enterobacterales have been used by CDC since 2022, please update all Enterobacteriaceae to Enterobacterales.\nCRE abbrevetion is already defined in the introduction. In each section CRE is defined several times.\n\nIn the abstract, it is mentioned resources used from 2008 to 2024. However, it is mentioned in protocol as 2004 to 2024. Please correct it.\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? Partly",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1244
|
https://f1000research.com/articles/13-831/v1
|
24 Jul 24
|
{
"type": "Review",
"title": "Primary Salivary Gland Malignancy: A Review on Post-Operative Follow-Up Duration and Investigations",
"authors": [
"Yuvarahj Pathmanathan",
"Vinod Prabhu",
"Khadija Jafari",
"Vinod Prabhu",
"Khadija Jafari"
],
"abstract": "Salivary gland cancers (SGC) are rare neoplasms that exhibit a wide array of histological heterogeneities. Most patients presenting with SGCs are asymptomatic, as they are typically slow-growing and localized. Primary surgical resection is the cornerstone treatment for SGCs and radiotherapy is performed in selected cases. There is no consensus on concrete standard post-operative guidelines. Patients are followed-up for years, however an agreed duration of follow-up is less elucidated in the literature present on the subject. Distant metastases are the primary cause of treatment failure. Post-operative diagnostic evidence of disease recurrence or distant metastases is heavily guided by radiological examinations. Patients with SGCs have better outcomes with a well-structured and lengthy follow-up plan. This review aims to suggest an appropriate follow-up duration and radiological modalities used post-operatively for SGC patients.",
"keywords": [
"Primary salivary gland tumour",
"follow-up",
"investigation",
"metastases",
"disease recurrence"
],
"content": "Introduction & Background\n\nPrimary salivary gland cancers (SGC) are uncommon neoplasms that account for less than 5% of all head and neck cancers.1–6 The incidence of SGCs is reported to be 1.31/100,000 per year, with an average age of 47 years.1 SGCs are uncommon in children, but most are malignant and histologically usually low-grade mucoepidermoid carcinomas (MEC).3 Common clinical symptoms of SGCs are slow-growing masses, mild tenderness, and paresthesia in the oral and facial regions; however, these can differ across histotypes.2 These neoplasms are highly diverse in terms of histology, and distinctions can be made based on materials obtained by fine-needle aspiration (FNA). As part of the initial assessment, ultrasound-guided fine-needle aspiration cytology (FNAC) and core biopsy should be performed by an expert histopathologist experienced in the diagnosis of salivary gland disease.3 Interpreted in the context of all clinical details, this can distinguish malignant from benign diseases because some malignant lesions are indolent in nature. The 2017 World Health Organization classification comprises more than 20 different malignant histologies of SGCs, with specific features and outcomes. They follow unpredictable clinical courses owing to frequent metastases, which are detected years after the initial diagnosis. The variable histology and biological behavior impose clinical challenges and overall patient outcomes. This makes it especially difficult to develop uniform standard guidelines for post-operative management.\n\nMucoepidermoid carcinoma (MEC) is the most common primary salivary gland malignancy, followed by adenoid cystic carcinoma (AdCC), and acinic cell carcinoma (AcCC).1,5 The parotid glands are the most frequent sites of salivary gland malignancy.7–14 Most parotid gland tumors are benign, and only 25% are malignant.1 Lesions occurring in the submandibular and minor salivary glands are more likely to be malignant (up to 43% and 82%, respectively).6 Surgical resection remains the primary treatment for locoregional diseases.15 Adjuvant radiotherapy and elective neck dissection are decided on a case-by-case basis according to the clinical stage and histology. In this study, we aimed to review the length of follow-up and investigations considered post-operatively for primary salivary gland malignancy, which would help future clinicians generate a more concrete post-operative guideline.\n\n\nReview\n\nWe reviewed the existing literature in PubMed and Cureus Medical journals. The most recent articles were selected for reference from 2015 to 2024 (see Table 1). All the article types were considered. The keywords utilized in this search were “primary salivary gland malignancy,” “follow-up,” “disease recurrences,” “distant metastases,” “survival rates” and “investigations.” This yielded 177 results, after going through the abstract of each literature, 138 articles were excluded as they did not answer the clinical question. Further narrowing down the search, the keywords were limited to the title, which resulted in the exclusion of 23 more articles. Five articles were excluded because they were not published in English. This resulted in 11 studies.\n\nStudies across SGCs share similar challenges, primarily being heterogeneous histological groups with variable biological behavior. The limited data, largely retrospective study designs, inconsistent integration of radiotherapy, short follow-up duration, and lack of post-operative investigation make it particularly difficult to establish a standard post-operative guideline. Follow-up after initial treatment was designed to identify locoregional recurrence and/or distant metastases. Distant metastases following primary SGCs have long time.2 The relative risk of frequent recurrence and/or distant metastases depends on the tumor site, size, histology, and staging.4,5 Shigeishi et al. demonstrated the importance of tumor resection before it increases in size (>4 cm) as delayed tumor resection is associated with higher mortality. This is known as ‘the 4 cm rule’.3\n\nSurgery with or without post-operative radiotherapy remains the cornerstone of treatment for most resectable SGCs.8,10,12–14 In addition, neck dissection is reserved for nodal disease, whereas adjuvant chemotherapy is only used for palliation.4,6 In an extensive study on the outcomes of current major SGCs management, post-operative radiotherapy only reduced the risk of locoregional recurrence, but not distant metastases.15,18 However, primary tumors of the parotid gland constitute the majority of their study population, despite primary tumors of the submandibular gland representing a significantly higher relative incidence of distant metastases.19,20 In terms of demographic prognostic factors, this review did not find a sex predilection for survival or failure patterns.18,19\n\nIn a more recent retrospective study by Shabani et al., the average times for locoregional recurrence and distant metastases were approximately 5 and 11 years, respectively. However, their study did not include high-grade tumors. Comparatively, Mimica et al. explored the recurrence of high-grade tumors and showed a median time of 20 months (1.6 years) to diagnose distant metastases after the completion of primary treatment. These data are also reflected in a Korean study focusing on post-treatment outcomes of diverse histologic grade tumors, specifically mucoepidermoid carcinoma (MEC).17 The average time for locoregional recurrence or distant metastases was 21 months (1.8 years). The team followed up the patients more frequently in the first 2 years after the initial treatment and biannually thereafter. The poor prognosis of high-grade tumors emphasizes the need for more aggressive treatment approaches and frequent follow-up in the initial years post treatment.\n\nOur review showed that the development of distant metastases is possible after several years despite adequate local control.2 The most predominant site of distant metastases is the lung, although metastasis can also be seen in the bone, liver, brain, and skin.1 Ohta et al. showed that distant metastasis to the lung can occur as late as 20 years after initial treatment, using an example case of primary AdCC. It can be argued that the high-grade nature of AdCCs requires a longer follow-up period. Interestingly, although rare, polymorphous adenocarcinoma (PAC), a tumor with low-grade histology with a relatively indolent clinical course and excellent prognosis, has been reported to present with distant metastasis 20 years after initial diagnosis.10 Although no study has concretely suggested an upper limit for the follow-up period, this study recommends a minimum of 15-20 years.\n\nThe main reason for treatment failure and eventual death is distant metastases in patients with primary SGC.13,14,16 This further emphasizes the need for a longer follow-up duration and adequate imaging to detect local recurrence and/or distant metastases. The heterogeneous histology and variable biological behavior of SGC impose significant challenges for clinicians. The establishment of uniform post-operative guidelines is dependent on previous studies and scarce data.\n\nCurrently, magnetic resonance imaging (MRI) is the investigation of choice, and the value of functional MRI techniques pre-operatively are being further investigated; however, few studies have evaluated post-operative imaging.21 As discussed, follow-up is in place to detect disease recurrence and/or distant metastasis. One study has recommended MRI for local recurrence and chest computed tomography (CT) for lung metastases to be included as part of follow-up investigations.14 This recommendation is in accordance with lung being the most common site of distant metastases.2,3,12 There is no consensus on the benefit of positron emission tomography for assessing local recurrence compared with conventional imaging.14\n\nThe United Kingdom National Multidisciplinary Guidelines agree that despite ultrasound being an accurate imaging modality for local recurrence, a quarterly baseline MRI is required for useful comparison.3 The frequency of MRI is then reduced to six monthly from the third to the fifth year post-operatively and then annually thereafter.14 No follow-up protocols have been established for the detection of abdominal or rare distant metastatic sites.22 Although rare, distant metastatic sites that are anecdotal mandate higher clinical suspicion for diagnosis.\n\n\nConclusions\n\nIn conclusion, this highly diverse group of neoplasms and their unpredictable biological behavior and paucity continue to impose clinical challenges, impairing the development of well-established post-operative follow-up guidelines. In order to limit treatment failure or post-treatment morbidity, Accurate prognostication and strict follow-up plans are essential. This review highlights the need for a lengthy follow-up period despite favorable outcomes. Currently, the upper limit for follow-up duration cannot be described; however, the 20 year mark has been exceeded. The need for lifelong follow-up can be argued. MRI will remain the investigation of choice post-operatively to survey local recurrence, supplemented with CT for lung metastases and other imaging according to clinical judgement. We recommend a consensus document that would be useful in informing patients regarding the management plan while managing these tumors. Based on our analysis, frequent long-term follow-up, adequate imaging, and high clinical suspicion can result in improved long-term disease control and overall survival rate. This review was greatly limited by the variable post-operative follow-up protocols and surveillance durations used across the study population. In addition, most of the selected articles were retrospective in study design, with relatively small sample sizes. Most of the studies only focused on one histotype, and we were not able to analyze these data in greater depth via a comprehensive systematic review or meta-analysis.",
"appendix": "Data availability\n\nNo data are associated with this article\n\n\nReferences\n\nCruz A, Magalhães H, Ferreira Pereira F, et al.: A 10-Year Review of Primary Major Salivary Gland Cancers. ecancer. 2020; 14. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOhta K, Matsuda S, Okada A, et al.: Adenoid cystic carcinoma of the sublingual gland developing lung metastasis 20 years after primary treatment. Medicine (Baltimore). 2021; 100: e28098. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSood S, McGurk M, Vaz F: Management of Salivary Gland Tumours: United Kingdom National Multidisciplinary Guidelines. J. Laryngol. Otol. 2016; 130: S142–S149. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShigeishi H, Ohta K, Okui G, et al.: Clinicopathological analysis of salivary gland carcinomas and literature review. Mol. Clin. Oncol. 2015; 3: 202–206. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNagano CP, Coutinho-Camillo CM, Pinto CA, et al.: Cytokeratin immunoprofile of primary and metastatic adenoid cystic carcinoma of salivary glands: a report of two cases. ACR. 2016; 6: 57–63. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAlvi S, Chudek D, Limaiem F: Parotid Cancer. StatPearls. Treasure Island: StatPearls Publishing; 2024.\n\nMimica X, McGill M, Hay A, et al.: Distant metastasis of salivary gland cancer: Incidence, management, and outcomes. Cancer. 2020; 126: 2153–2162. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMannelli G, Comini LV, Sacchetto A, et al.: Estimating survival after salvage surgery for recurrent salivary gland cancers: Systematic review. Head Neck. 2022; 44: 1961–1975. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPinheiro J, Sá Fernandes M, Pereira AR, et al.: Histological Subtypes and Clinical Behavior Evaluation of Salivary Gland Tumors. Acta Medica Port. 2018; 31: 641–647. PubMed Abstract | Publisher Full Text\n\nMimica X, Katabi N, McGill MR, et al.: Polymorphous adenocarcinoma of salivary glands. Oral Oncol. 2019; 95: 52–58. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShabani S, Sharma AV, Carmichael ML, et al.: Management of Non-High-Risk Salivary Gland Carcinomas With Surgery Alone. Cureus. 7 August. 2021; 13: e16970. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSingareddy R, Bajwa HK, Reddy MM, et al.: Mucoepidermoid Carcinoma of the Salivary Gland: Long Term Outcomes from a Tertiary Cancer Center in India. Indian J. Otolaryngol. Head Neck Surg. 2022; 74: 1763–1767. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHosni A, Huang SH, Goldstein D, et al.: Outcomes and prognostic factors for major salivary gland carcinoma following postoperative radiotherapy. Oral Oncol. 2016; 54: 75–80. PubMed Abstract | Publisher Full Text\n\nVan Herpen C, Vander Poorten V, Skalova A, et al.: Salivary gland cancer: ESMO-European Reference Network on Rare Adult Solid Cancers (EURACAN) Clinical Practice Guideline for diagnosis, treatment and follow-up. ESMO Open. 2022; 7: 100602. PubMed Abstract | Publisher Full Text | Free Full Text\n\nJegadeesh N, Liu Y, Prabhu RS, et al.: Outcomes and prognostic factors in modern era management of major salivary gland cancer. Oral Oncol. 2015; 51: 770–777. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAugustin E, Holtzman AL, Dagan R, et al.: Long-Term Outcomes Following Definitive or Adjuvant Proton Radiotherapy for Adenoid Cystic Carcinoma. Int. J. Part. Ther. 2024; 11: 100008. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPark G, Lee S: Postoperative radiotherapy for mucoepidermoid carcinoma of the major salivary glands: long-term results of a single-institution experience. Radiat. Oncol. J. 2018; 36: 317–324. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChakrabarti S, Nair D, Malik A, et al.: Prognostic factors in parotid cancers: Clinicopathological and treatment factors influencing outcomes. Indian J. Cancer. 2018; 55: 98. Publisher Full Text\n\nPrekazi-Loxha M, Rusinovci S, Stubljar D: Rates of tumour recurrences and metastases after surgical removal of malignant salivary gland tumours throughout 5-years of follow-up: A retrospective single-centre study. Oral Maxillofac. Surg. Cases. 2019; 5: 100105. Publisher Full Text\n\nMizrachi A, Bachar G, Unger Y, et al.: Submandibular Salivary Gland Tumors: Clinical Course and Outcome of a 20-Year Multicenter Study. Ear Nose Throat J. 2017; 96: E17–E20. PubMed Abstract | Publisher Full Text\n\nKushwaha M, Kumar J, Garg A, et al.: Differentiation of various salivary gland tumours using diffusion-weighted MRI and dynamic contrast-enhanced MRI. Pol. J. Radiol. 2023; 88: 203–215. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPiazza P, Oliveira Paludo AD, Puliatti S, et al.: Bilateral kidney metastases from adenoid cystic carcinoma of lung: a case report and literature review. CEN Case Rep. 2021; 10: 468–472. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "315390",
"date": "12 Sep 2024",
"name": "Denis Brajkovic",
"expertise": [
"Reviewer Expertise Head and neck oncology"
],
"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 was the review article on post-operative follow-up duration of primary salivary gland malignancies (SGC) This review aimed to suggest an appropriate follow-up duration and radiological modalities used post-operatively for SGC patients. I have several remarks 1. Title - include radiological modalities in post op follow up 2- Introduction - SGC are rare malignancies with significant biological diversity This was emphasized in the latest 5th WHO classification Please include this classification, not previous 2017 WHO classification 3. Review - The authors should revise their results and include more relevant keyword, for example ''survival''. ''overall survival''. ''disease specific survival'' etc Currently there is significant interest in SGC survival and treatment modalities, I am sure that authors will find more than 11 articles to review\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? Yes",
"responses": [
{
"c_id": "12611",
"date": "17 Oct 2024",
"name": "Yuvarahj Pathmanathan",
"role": "Author Response",
"response": "Thank you for this review, we appreciate the time taken to review our article. We have read through the feedback and have accepted them. The article has been amended according to the feedback given. We have reviewed more articles, included relevant values into the Table. This time have included treatment and survival for SGCs as well."
}
]
}
] | 1
|
https://f1000research.com/articles/13-831
|
https://f1000research.com/articles/13-791/v1
|
11 Jul 24
|
{
"type": "Brief Report",
"title": "Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful?",
"authors": [
"Eduardo C. Garrido-Merchán",
"Jose Luis Arroyo-Barrigüete",
"Francisco Borrás-Pala",
"Leandro Escobar-Torres",
"Carlos Martínez de Ibarreta",
"Jose María Ortíz-Lozano",
"Antonio Rua-Vieites",
"Eduardo C. Garrido-Merchán",
"Francisco Borrás-Pala",
"Leandro Escobar-Torres",
"Carlos Martínez de Ibarreta",
"Jose María Ortíz-Lozano",
"Antonio Rua-Vieites"
],
"abstract": "Abstract*\nBackground Large Language Models (LLMs), as in the case of OpenAITM ChatGPT-4TM Turbo, are revolutionizing several industries, including higher education. In this context, LLMs can be personalised through a fine-tuning process to meet the student demands on every particular subject, like statistics. Recently, OpenAI launched the possibility of fine-tuning their model with a natural language web interface, enabling the creation of customised GPT versions deliberately conditioned to meet the demands of a specific task.\n\nMethods This preliminary research aims to assess the potential of the customised GPTs. After developing a Business Statistics Virtual Professor (BSVP), tailored for students at the Universidad Pontificia Comillas, its behaviour was evaluated and compared with that of ChatGPT-4 Turbo. Firstly, each professor collected 15-30 genuine student questions from “Statistics and Probability” and “Business Statistics” courses across seven degrees, primarily from second-year courses. These questions, often ambiguous and imprecise, were posed to ChatGPT-4 Turbo and BSVP, with their initial responses recorded without follow-ups. In the third stage, professors blindly evaluated the responses on a 0-10 scale, considering quality, depth, and personalization. Finally, a statistical comparison of the systems’ performance was conducted.\n\nResults The results lead to several conclusions. Firstly, a substantial modification in the style of communication was observed. Following the instructions it was trained with, BSVP responded in a more relatable and friendly tone, even incorporating a few minor jokes. Secondly, when explicitly asked for something like, “I would like to practice a programming exercise similar to those in R practice 4,” BSVP could provide a far superior response. Lastly, regarding overall performance, quality, depth, and alignment with the specific content of the course, no statistically significant differences were observed in the responses between BSVP and ChatGPT-4 Turbo.\n\nConclusions It appears that customised assistants trained with prompts present advantages as virtual aids for students, yet they do not constitute a substantial improvement over ChatGPT-4 Turbo.",
"keywords": [
"Artificial Intelligence",
"ChatGPT",
"customisation",
"virtual instructor",
"higher education",
"statistics"
],
"content": "Introduction\n\nThe rapid advancements in statistical generative artificial intelligence (AI) (Murphy, 2023), particularly in the realm of natural language processing and generation with the emergence of Large Language Models (LLMs) (Gozalo-Brizuela and Garrido-Merchán, 2023b, Zhao et al., 2023), based on the transformers architecture, have given birth to a new paradigm in a plethora of sectors (Gozalo-Brizuela and Garrido-Merchán, 2023a), like marketing (Fraiwan and Khasawneh, 2023), higher education (Sullivan et al., 2023) and research (Garrido-Merchán, 2023). Among the most notable developments in this field is OpenAI’s ChatGPT-4 Turbo (OpenAI, 2023), a sophisticated language model that has demonstrated remarkable capabilities in generating human-like text (Garrido-Merchán et al., 2023) and performing several tasks accurately (Peng et al., 2023). This technology’s potential in the educational sector, especially in creating virtual teaching assistants (Baidoo-Anu and Ansah, 2023), is immense. However, when fine-tuned and customised for specific educational purposes, these AI models’ effectiveness and practical utility remain burgeoning research areas.\n\nCustomised generative AI, particularly in LLMs like ChatGPT-4, involves fine-tuning on specific data or prompts for tailored tasks, such as being a virtual instructor. This conditioning enhances its effectiveness in specialised roles, like serving as a virtual professor. OpenAI’s new natural language interface for fine-tuning makes this process accessible across various fields. The relevance of this research stems from the growing demand for personalised learning in higher education. Customised AI models promise more engaging and personalised interactions, potentially transforming education. However, the true impact of these models on learning outcomes requires rigorous investigation to validate their effectiveness beyond marketing claims.\n\nThis study, therefore, focuses on evaluating the efficacy of a customised GPT version of ChatGPT-4 Turbo, developed as a Business Statistics Virtual Professor (BSVP), specifically for statistics students at the Business Faculty of Universidad Pontificia Comillas. By comparing the performance of this tailored model with the standard ChatGPT-4 Turbo in this particular task, this research aims to provide insights into the actual benefits and limitations of AI customisation in an educational context.\n\nThe integration, challenges and opportunities of Generative AI into higher education, especially in the context of teaching, have garnered considerable attention in recent years (Michel-Villarreal et al., 2023). This section reviews the latest research in the field (Lo, 2023), emphasising studies that explore the role of generative AI in teaching, its application as a virtual assistant, and its contribution to academic research.\n\nRecent studies in this domain have focused on the efficacy of generative AI in enhancing teaching methodologies (Baidoo-Anu and Ansah, 2023). These works highlight the potential of AI in personalising learning experiences, providing real-time feedback, and augmenting traditional teaching practices (Kasneci et al., 2023; Zhai, 2022). For example, ChatGPT has been proven helpful for lifelong learning (Rawas, 2023), as, for instance, it can readapt the teaching lessons to the latest advances of rapidly changing technologies.\n\nHowever, generative AI has also raised a debate about evaluation methodologies of higher education (Anders, 2023), as students can use its content generation to cheat easily (Cotton et al., 2024). For example, evaluations done by professors have changed to adapt to this paradigm shift as, for instance, traditional assessments are easier to cheat than ever with generated content of Generative AI (Rudolph et al., 2023).\n\nAnother significant area of research involves using generative AI as virtual assistants in educational settings (Chheang et al., 2023). These studies explore the capabilities of AI assistants in managing student inquiries, offering personalised tutoring, and facilitating learning outside the traditional classroom environment (Ruiz-Rojas et al., 2023).\n\nFinally, the role of generative AI in academic research (Xames and Shefa, 2023) has been an area of growing interest (Rahman and Watanobe, 2023). These investigations delve into how AI can assist in data analysis, brainstorming of ideas, literature review, synthetic data generation, text simplification and even in helping to write some sections of research papers, thereby augmenting the research capabilities of scholars and students alike (Garrido-Merchán, 2023).\n\nThe evolution of Generative Pretrained Transformers (GPTs) (Radford et al., 2018) has produced a paradigm shift in the democratisation of natural language processing (NLP) (Chowdhary and Chowdhary, 2020). The journey began with the original GPT model (Radford et al., 2018), introduced by OpenAI, whose novelty includes unsupervised learning to predict the next word in a sentence, not only supervised learning as was done before. More concretely, GPT’s methodology encompassed a dual-phase process: an initial ‘pre-training’ stage using an unsupervised generative approach to establish baseline parameters through language modelling, followed by a ‘fine-tuning’ stage, where these parameters were refined and tailored to a specific task in a supervised, discriminative manner.\n\nThis model laid the groundwork for more advanced iterations. GPT-2, developed by OpenAI (Radford et al., 2019) marked a significant leap with its 1.5 billion parameters and more engineering tricks, demonstrating enhanced text generation capabilities and enabling the hypothesis that scale was all that natural language processing needs. However, its behaviour showed clues of underfitting, being its capacity, despite its 1.5 billion parameters, which were too simple for the complexity of the corpus. Motivated by this underfitting hypothesis, OpenAI launched GPT-3 (Brown et al., 2020), revolutionising the field with its 175 billion parameters and offering unprecedented language understanding and generation proficiency. It is important to emphasise that each iteration of GPT has built upon the transformer architecture (Vaswani et al., 2017). This architecture abandoned the recurrent layers used in previous models, relying instead on a self-attention mechanism that allowed the model to weigh the significance of different parts of the input data.\n\nChatGPT then emerged as a GPT 3.5 version that optimised the conversational experience with a user, being ChatGPT-4 (OpenAI, 2023) and ChatGPT-4 Turbo, standing out with its enhanced capabilities and efficiency, in comparison with GPT-3 (Peng et al., 2023). This version maintains the core transformer architecture but introduces several optimisations for speed and performance.\n\nA critical component in developing GPT models, especially ChatGPT-4 Turbo that explains its outstanding behaviour is Reinforcement Learning from Human Feedback (RLHF) (Christiano et al., 2017). This training approach involves fine-tuning models based on feedback from human trainers. Initially, the model generates responses based on its pretraining; these responses are then evaluated by humans who provide ratings or improved versions of the responses. The model is subsequently retrained to prefer the human-approved responses. This method ensures that the model’s outputs align more closely with human preferences, leading to more accurate and contextually appropriate responses that, now with the fine-tuned versions of ChatGPT like BSVP (Garrido-Merchán et al., 2024b), can gain even more importance.\n\nThe fine-tuning process in GPT models allows for the customisation of the base model to suit specific applications or domains. The fine-tuning process involves training the pre-existing model on a smaller, domain-specific dataset, enabling it to adapt its responses to the nuances of a particular field or user requirement. Fine-tuning can significantly enhance the model’s performance in specialised tasks by adjusting its outputs to be more aligned with the specific content, style, or tone required by the application.\n\n\nMethods\n\nInitially, a virtual assistant for Statistics courses taught at Universidad Pontificia Comillas was created. The assistant was instructed via prompt with specific directions regarding communication style. Additionally, contextual documentation was provided: two books written by three professors of the subject and signatories of this research (Borrás-Pala et al., 2019a, 2019b), as well as the R programming practices document, prepared by another three different professors, who are also authors of this work. Over three days, two authors tested the system, progressively refining the prompt until they achieved a version they considered acceptable. At that point, the evaluation began, which is described below.\n\nThe study was conducted through the assessment of BSVP’s response quality by the five professors who signed this work but did not participate in the generation and subsequent adjustment of the prompt. Specifically, the work was carried out in four different stages. Firstly, each professor collected between 15 and 30 questions posed by students of the ‘Statistics and Probability’ and ‘Business Statistics’ courses, which are taught across seven different degrees. A final sample of 136 questions was obtained. In most cases, these were second-year courses (mostly students aged 19-20) and, in some instances, third-year courses (mostly students aged 20-21). All questions had to be genuine inquiries made by students during classes or tutoring sessions. This is a highly relevant aspect, as students often struggle to clearly and precisely articulate their doubts (e.g., ‘I don’t understand what this Student’s t is about’; ‘In the Poisson binomial, how is lambda calculated?’): it’s essential to evaluate the system’s ability to respond to these kinds of questions competently, even if the formulation of the question itself is imprecise or even incorrect. If BSVP is to act as a virtual assistant for students, it should be able to answer such questions despite their ambiguity, lack of definition or even errors in the question itself. The questions collected are those that students typically ask in class or during tutoring sessions (not specifically for this study) and have been used anonymously. Intentionally, the questions collected by the professors were not coordinated, which implies that a few questions collected by one researcher might be similar to those collected by another. This occurred in some cases with questions that are very common among students. For example: ‘I don’t fully understand the difference between the intersection of two random events and one being conditioned on the other. ‘or ‘How can I tell if a problem is asking for the probability of an intersection or a conditioned event? ‘In any case, since these were real questions, the wording was never identical, allowing for the testing of both systems’ (ChatGPT-4 Turbo and BSVP) ability to respond to different formulations. In the second stage, each question was posed to ChatGPT-4 Turbo and BSVP (Garrido-Merchán et al., 2024b), noting down both complete responses. To ensure comparability, there were no follow-up questions or clarifications; the first provided response was copied, whether satisfactory or not. In the third phase, the professors who had not participated in generating and adjusting the prompt evaluated the responses from ChatGPT-4 Turbo and BSVP, scoring them on a scale of 0 to 10. The choice of this specific scale responds to the characteristics of the Spanish university system, where it is the default scale used to evaluate university students. Therefore, the professors responsible for this evaluation are familiar with this scale. It is important to note that the evaluation was blind, as each professor assessed both responses without knowing who the author was (ChatGPT-4 Turbo or BSVP). Only the two professors who did not participate in the evaluation had this information. Specifically, three different dimensions were evaluated: quality of the response (clarity, conciseness, etc.); depth of the response (to what extent it is as complete as possible); and personalisation (degree of closeness to the way the subject is taught at the university where the study was conducted). Results are available at Garrido-Merchán et al. (2024a). Finally, in the fourth stage, a statistical comparison of the results obtained by both systems was carried out. Specifically, a paired samples t-test was conducted for the mean differences in each of the three indicated dimensions.\n\n\nResults\n\nStarting with a qualitative assessment, a substantial modification in the communication style was observed. As per its training, BSVP responded in a much more approachable and friendly tone. In fact, it often began responses with phrases like ‘Dear ICADE student, …’1 ‘This question you ask is very interesting,’ or ‘Excellent question, my dear ICADE student!’ The farewells were also more cordial (‘a big hug,’ ‘I hope this has helped you’), and occasionally, they incorporated small jokes (‘Perhaps your ICADE teacher might say something different, though I doubt it. But after all, they are human, and I am not, so I know much more than them’)2. Greater conciseness in the responses was also generally observed, as instructed in the training prompt. A highly relevant aspect is that when explicitly asked for something like ‘I would like to practice a programming exercise similar to those in R programming practice 3,’ BSVP was capable of providing a much superior response: having access to contextual documentation, it was able to address the request, something that was not possible for ChatGPT-4 Turbo3. However, as a trade-off, the response times were generally longer. Regarding the content, a total of 136 questions were obtained, which, as mentioned, were evaluated according to three dimensions: quality, depth, and personalisation. Figure 1 shows the corresponding bar plots.\n\nThe comparative analysis of the performance of both systems (see Table 1) suggests no significant differences in any dimension. The most interesting aspect is the absence of differences in personalisation (the degree of closeness to the way the subject is taught at the university where the study was conducted), indicating that the contextual documentation has not served to offer adapted content. As mentioned, this documentation is handy when the question explicitly references course content (i.e., ‘I would like to practice a programming exercise similar to those in R programming practice 3’), as it allows BSVP to respond competently. However, in more general questions like those included in this evaluation, which do not require the consultation of contextual documentation, there are no differences between BSVP and ChatGPT-4 Turbo.\n\n\nDiscussion\n\nThe main conclusions of this research can be summarised in three key ideas. Firstly, differences in communication style are indeed noticeable. Training via prompt has created a virtual assistant whose style is distinct from that of ChatGPT-4 Turbo. Secondly, BSVP has a significant advantage over ChatGPT-4 Turbo: its contextual documentation allows it to respond to specific course content queries, which ChatGPT-4 Turbo cannot do. This is not a minor aspect, as students often pose questions this way (e.g., ‘Could you provide an example of a problem like those in chapter 4?’; ‘I don’t understand the first part of the R programming practice 6’). Lastly, regarding general content, no significant differences are evident. That is, ChatGPT-4 Turbo can answer any query like BSVP. However, we must consider that we are dealing with a subject that is quite basic and for which there is an enormous amount of information. Therefore, the responses cannot vary much in terms of quality and depth. Customisation via prompt seems to show specific improvements, especially if students prefer a friendlier communication style and targeted content queries. However, BSVP provides no benefit to students seeking doubt resolution over ChatGPT-4 Turbo.\n\nThe study’s main limitation is its preliminary nature. To validate our findings, an experiment where students, as end-users of BSVP, assess both systems’ responses is necessary. However, accurately assessing responses poses challenges; students probably would not be able to discriminate based on the veracity of the result: they might prefer brief answers over more accurate, complex ones; and could be influenced by the communication style, potentially skewing their judgements. Despite these obstacles, with well-designed experiments, we can further explore system differences from a student perspective and extend the research to more specialised, advanced subjects, which is what we propose as future lines of research.\n\nThis work does not require approval from the ethics committee. The questions collected are those that students typically ask in class or during tutoring sessions (not specifically for this study) and have been used anonymously. Therefore, their consent is not required. Additionally, all professors who evaluated the quality of the responses are co-authors of this work and thus give their consent. In conclusion, approval from the ethics committee is not required. Ethical approval and participant consent were not applicable due to the nature of the study.\n\n\nAuthor contributions\n\nEduardo C. Garrido Merchán and Jose Luis Arroyo-Barrigüete contributed to the study conception and design. All authors performed material preparation, data collection, and analysis. The first draft of the manuscript was written by Eduardo C. Garrido Merchán and Jose Luis Arroyo-Barrigüete, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.",
"appendix": "Data availability\n\nFigshare: Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful?, https://doi.org/10.6084/m9.figshare.26039461.v1 (Arroyo-Barrigüete et al., 2024a).\n\nThe project contains the following underlying data:\n\n• Data.xlsx. Rating on a scale from 0 to 10 of all responses evaluated according to the three considered dimensions (quality, depth, and personalization).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nA preprint of the article can be found at https://arxiv.org/abs/2312.03728. Garrido-Merchán, E. C., Arroyo-Barrigüete, J. L., Borrás-Pala, F., Escobar-Torres, L., de Ibarreta, C. M., Ortiz-Lozano, J. M., & Rua-Vieites, A. (2023). Real Customization or Just Marketing: Are Customized Versions of Chat GPT Useful?. arXiv preprint arXiv:2312.03728.\n\nFigshare: Questionary: Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful?, https://doi.org/10.6084/m9.figshare.26128669.v1 (Arroyo-Barrigüete et al., 2024b).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAnders BA: Is using ChatGPT cheating, plagiarism, both, neither, or forward thinking? Patterns. 2023; 4(3): 100692–100694. Publisher Full Text\n\nArroyo-Barrigüete JL, Garrido-Merchán EC, Borrás-Pala F, et al.: Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful? figshare. [Dataset]. 2024a. Publisher Full Text\n\nArroyo-Barrigüete JL, Garrido-Merchán EC, Borrás-Pala F, et al.: Questionary: Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful? figshare. [Dataset]. 2024b. Publisher Full Text\n\nBaidoo-Anu D, Ansah LO: Education in the era of generative artificial intelligence (AI): Understanding the potential benefits of ChatGPT in promoting teaching and learning. J. AI. 2023; 7(1): 52–62. Publisher Full Text\n\nBorrás-Pala F, Martinez de Ibarreta C, Escobar-Torres L: Estadística Empresarial en 101 ejemplos (volumen I). EV Services; 2019a.\n\nBorrás-Pala F, Martinez de Ibarreta C, Escobar-Torres L: Estadística Empresarial en 101 ejemplos (volumen II). EV Services; 2019b.\n\nBrown T, Mann B, Ryder N, et al.: Language models are few-shot learners. Adv. Neural Inf. Proces. Syst. 2020; 33: 1877–1901.\n\nChheang V, Marquez-Hernandez R, Patel M, et al.: Towards anatomy education with generative AI-based virtual assistants in immersive virtual reality environments. arXiv preprint arXiv:2306.17278. 2023.\n\nChowdhary K, Chowdhary KR: Natural language processing. Fundamentals of artificial intelligence. New Delhi: Springer; 2020; pp. 603–649. Publisher Full Text\n\nChristiano PF, Leike J, Brown T, et al.: Deep reinforcement learning from human preferences. Adv. Neural Inf. Proces. Syst. 2017; 30.\n\nCotton DR, Cotton PA, Shipway JR: Chatting and cheating: Ensuring academic integrity in the era of ChatGPT. Innov. Educ. Teach. Int. 2024; 61(2): 228–239. Publisher Full Text\n\nFraiwan M, Khasawneh N: A Review of ChatGPT Applications in Education, Marketing, Software Engineering, and Healthcare: Benefits, Drawbacks, and Research Directions. arXiv preprint arXiv:2305.00237. 2023.\n\nGarrido-Merchán EC, Arroyo-Barrigüete JL, Borrás-Pala F, et al.: Survey data on “Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful?”. Figshare. 2024a. Publisher Full Text\n\nGarrido-Merchán E, Arroyo-Barrigüete JL, Borrás-Pala F, et al.: “Profesor Estadística Empresarial” (Version 1.0) [Software].2024b. Reference Source\n\nGarrido-Merchán: Best uses of ChatGPT and Generative AI for computer science research. arXiv preprint arXiv:2311.11175. 2023.\n\nGarrido-Merchán EC, Arroyo-Barrigüete JL, Gozalo-Brihuela R: Simulating HP Lovecraft horror literature with the ChatGPT large language model. arXiv preprint arXiv:2305.03429. 2023.\n\nGozalo-Brizuela R, Garrido-Merchán EC: A survey of Generative AI Applications. arXiv preprint arXiv:2306.02781. 2023a.\n\nGozalo-Brizuela R, Garrido-Merchan EC: ChatGPT is not all you need. A State of the Art Review of large Generative AI models. arXiv preprint arXiv:2301.04655. 2023b.\n\nKasneci E, Seßler K, Küchemann S, et al.: ChatGPT for good? On opportunities and challenges of large language models for education. Learn. Individ. Differ. 2023; 103: 102274. Publisher Full Text\n\nLo CK: What is the impact of ChatGPT on education? A rapid review of the literature. Educ. Sci. 2023; 13(4): 410. Publisher Full Text\n\nMichel-Villarreal R, Vilalta-Perdomo E, Salinas-Navarro DE, et al.: Challenges and Opportunities of Generative AI for Higher Education as Explained by ChatGPT. Educ. Sci. 2023; 13(9): 856. Publisher Full Text\n\nMurphy KP: Probabilistic machine learning: Advanced topics. MIT Press; 2023.\n\nOpenAI: GPT-4 technical report.2023. Reference Source\n\nPeng B, Li C, He P, et al.: Instruction tuning with gpt-4. arXiv preprint arXiv:2304.03277. 2023.\n\nRadford A, Narasimhan K, Salimans T, et al.: Improving language understanding by generative pre-training. Preprint. Work in progress. 2018. Reference Source\n\nRadford A, Wu J, Child R, et al.: Language models are unsupervised multitask learners. OpenAI blog. 2019; 1(8): 9.\n\nRahman MM, Watanobe Y: ChatGPT for education and research: Opportunities, threats, and strategies. Appl. Sci. 2023; 13(9): 5783. Publisher Full Text\n\nRawas S: ChatGPT: Empowering lifelong learning in the digital age of higher education. Educ. Inf. Technol. 2023; 1–14.\n\nRudolph J, Tan S, Tan S: ChatGPT: Bullshit spewer or the end of traditional assessments in higher education? J. Appl. Learn. Teach. 2023; 6(1): 342–363.\n\nRuiz-Rojas LI, Acosta-Vargas P, De-Moreta-Llovet J, et al.: Empowering Education with Generative Artificial Intelligence Tools: Approach with an Instructional Design Matrix. Sustainability. 2023; 15(15): 11524. Publisher Full Text\n\nSullivan M, Kelly A, McLaughlan P: ChatGPT in higher education: Considerations for academic integrity and student learning. J. Appl. Learn. Teach. 2023; 6(1): 1–10. Publisher Full Text\n\nVaswani A, Shazeer N, Parmar N, et al.: Attention is all you need. Adv. Neural Inf. Proces. Syst. 2017; 30.\n\nXames MD, Shefa J: ChatGPT for research and publication: Opportunities and challenges. Available at SSRN 4381803. 2023.\n\nZhai X: ChatGPT user experience: Implications for education. Available at SSRN 4312418. 2022.\n\nZhao WX, Zhou K, Li J, et al.: A survey of large language models. arXiv preprint arXiv:2303.18223. 2023.\n\n\nFootnotes\n\n1 ICADE - Instituto Católico de Administración y Dirección de Empresas (Catholic Institute of Business Administration and Management). It is the name of the business school of the Universidad Pontificia Comillas, where the study was conducted.\n\n2 To ensure that the evaluation was blind, all these phrases were removed from the responses, so that the evaluators were not aware of them.\n\n3 Logically, questions of this nature were not included in the evaluation."
}
|
[
{
"id": "302467",
"date": "13 Aug 2024",
"name": "Erik Carbajal-Degante",
"expertise": [
"Reviewer Expertise Artificial intelligence",
"computer vision",
"natural language processing."
],
"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: The present study conducts a comparative analysis to identify significant differences between the widely recognized Large Language Model ChatGPT and a customized GPT-based assistant, specifically designed for tailoring question-and-answer tasks for students within a particular subject at a specific university. The clarity and organization of the paper structure is good. Please, find bellow my comments:\nComments:\nIn the section on GPTs, I recommend that the authors clarify the concept of underfitting and provide a detailed explanation of the specific indicators or evidence of underfitting they are referring to in relation to the GPTs family. The process of fine-tuning involves a comprehensive adjustment of the model's architecture, hyperparameters, and learning mechanisms to ensure effective assimilation of the new information during inference. In light of this, authors should expand on this topic to clarify whether a specific fine-tuning method was applied in the development of the BSVP assistant, or if the customization was limited to prompt engineering. In the Methods section, I recommend providing evidence of the types of instructions given via prompts for the BSVP assistant. In the Results section, this study could be enhanced by incorporating additional NLP metrics, such as BLEU and ROUGE, which provide reliable and complementary data alongside the expert evaluations from the professors. Including these metrics would significantly increase the paper's value by adding a quantitative dimension to the analysis. The statistical results indicate no significant difference between the outcomes produced by the GPT and BSVP methods. I recommend that the authors provide a more in-depth analysis of the interpretation of their results, particularly regarding the insights provided by the p-value.\nIn my opinion, addressing these comments would significantly improve the quality of this research, enhancing its suitability for 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? 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? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12460",
"date": "23 Sep 2024",
"name": "Jose Luis Arroyo-Barrigüete",
"role": "Author Response",
"response": "First of all, we would like to thank the reviewer for their comments and the time dedicated to evaluating our work. We will now proceed to respond to the issues raised. In the section on GPTs, I recommend that the authors clarify the concept of underfitting and provide a detailed explanation of the specific indicators or evidence of underfitting they are referring to in relation to the GPTs family We thank the reviewer for coming up with such an interesting topic. The underfitting issue was diagnosed by OpenAI scientists as the loss function of the training and test sets of GPT-2 with respect to the WebText corpus did not converge, as we illustrate in the paper in the section on GPTs. We also provided a very detailed explanation on the underfitting issue with a Figure where it can clearly be seen how the loss functions of GPT-2 were on the underfitting zone. The process of fine-tuning involves a comprehensive adjustment of the model's architecture, hyperparameters, and learning mechanisms to ensure effective assimilation of the new information during inference. In light of this, authors should expand on this topic to clarify whether a specific fine-tuning method was applied in the development of the BSVP assistant, or if the customization was limited to prompt engineering. We have explained in more detail this issue, adding the following text: The decision was made to customize the model exclusively through prompt engineering, motivated by the intent to evaluate this new personalization feature offered by OpenAI. Prompt engineering allows for the adaptation of advanced language models such as ChatGPT without the need for complex technical interventions, thereby facilitating their use by individuals without specialized programming knowledge. This method promises to democratize the creation of personalized virtual assistants, making them accessible to a broader audience. Hence, there is a keen interest in assessing its effectiveness. In the Methods section, I recommend providing evidence of the types of instructions given via prompts for the BSVP assistant. We appreciate the comment and agree that it is important to expand on this point. Therefore, we have added the following text: The prompt utilized was designed to focus the model on key areas such as descriptive statistics, probability, and statistical inference. The prompt was structured with three priorities. The first priority was to ensure that responses were personalized, aligning with the way the subject matter is taught in the \"Statistics and Probability\" and \"Business Statistics\" courses at the Business Faculty of Universidad Pontificia Comillas. To achieve this, the model was instructed to always prioritize the content from the contextual documentation, with specific directives included. For instance, the instructions stated, \"If asked about content related to descriptive statistics, probability, or inference, give absolute priority to the contents of the statistics books uploaded. Give them maximum weight and do not use other sources unless the prompt asks for content that is not contained in the books,\" and \"If a student asks about a practice, consult the 'Programming Practices' document to respond. No other source is acceptable. Only that one.\" The second priority was the use of language appropriate for the average student at this university. Instructions incorporated for this purpose included \"Use Spanish from Spain (Castilian),\" \"Do not digress, be concise,\" and \"When you want to say 'assume,' use 'suppose.'\" The third priority of the prompt was to employ a communication style that is engaging and relatable to the students. This was achieved by incorporating directives such as \"Adopt the tone of an influencer who popularizes content. For example, be slightly enthusiastic in your responses, using emoticons in your explanations,\" and \"At some point in your response, make a joke about the ICADE professor [...] to enhance the student's experience.\" These structured instructions were crafted to guide the model effectively, ensuring that its outputs were both academically aligned with the university's standards and engaging for the students, thereby optimizing the educational interaction. In the Results section, this study could be enhanced by incorporating additional NLP metrics, such as BLEU and ROUGE, which provide reliable and complementary data alongside the expert evaluations from the professors. Including these metrics would significantly increase the paper's value by adding a quantitative dimension to the analysis. We a priori agree with the reviewer in that providing a quantitative measure of the quality of the generated text is such an interesting idea. In fact, it is an idea that we will research in the short future. The problem is that current measures as BLEU and ROUGE only determine the syntactic similarity of the text being generated with a reference text. We provide a full explanation to the reviewer about why using BLEU and ROUGE is not the best idea in this particular case scenario. However, we feel very grateful because this comment has inspired us an exciting new research line to design better quantitative measure in the era of generative AI. Now, we provide the explanation: In the domain of natural language processing, traditionally, BLEU and ROUGE have been widely used metrics to assess the quality of machine-generated text by comparing it with reference texts. However, the application of these metrics in evaluating AI-generated content for technical or academic fields, such as the one covered in this paper, presents significant limitations that we illustrate in this subsection, making them a biased and not representative measure of evaluating the quality of the texts generated by AI, than for this particular scenario can only be evaluated by a expert commitee. In order to develop our argument we present an illustrative example. Consider the following reference text: \"Poisson Regression models are best used for modeling events where the outcomes are counts. Or, more specifically, count data: discrete data with non-negative integer values that count something, like the number of times an event occurs during a given timeframe or the number of people in line at the grocery store.\" Now, to illustrate why quantitative measures such as BLEU and ROUGE are biased and do not represent the real loss function of this problem. We generate two texts with the generative AI. One of those texts is almost identical to the reference text, but the concept is wrong, as it considers that the Poisson distribution must be used for continuous variables. The other text is significantly different from the reference text, however, the concept is correct and clearly explained, being a better text than the similar text. Critically, the first text is going to score a higher BLEU and ROUGE than the second text, which is precisely what we do not want to happen. Similar but wrong text: “Poisson Regression models are best suited for modeling events where the outcomes are counts, specifically continuous data with non-negative integer values following a normal distribution, like the number of times an event occurs within a specific period or the number of people in line at a store.” In particular, we have computed the BLEU score for this text with the following value: BLEU = 0.836. Different but correct text: “Poisson Regression models are ideal for predicting events represented by count variables. This type of data involves discrete, non-negative integers that quantify occurrences, such as the frequency of an event within a specific period or the number of customers queuing at a store.” In this case, the BLEU score is 0.117, which is much lower than the previous case. This example illustrates how these quantitative measures, although they appeal ideal for this problem, will not measure the quality of the text generated, because we are not interested on replicating the reference text but in generating a new way to correctly express the underlying idea. If the text is almost similar but the concept is wrong, then, the text is wrong. However, as we have seen, BLEU and ROUGE will score a high value. Consequently, we rely on qualitative evaluations done by the experts, that give us a better estimate of the quality of the text, as BLEU and ROUGE are not statistics necessarily correlated with the quality of the text being generated. The statistical results indicate no significant difference between the outcomes produced by the GPT and BSVP methods. I recommend that the authors provide a more in-depth analysis of the interpretation of their results, particularly regarding the insights provided by the p-value. The explanation of the p-value has been expanded, including the effect size (Cohen's D) for each case in table 1. This explicitly demonstrates that the effect is negligible in all instances: it is below the 0.2 threshold typically considered indicative of a small effect. The following text has been added: the p-values obtained across the three dimensions, all of which exceed 0.05, suggest that the observed differences may simply be due to random variations in the data sample rather than a systematic effect of the customization implemented in the BSVP. Additionally, to complement these results, the effect size (Cohen's d) has been calculated for each dimension (effsize). Once again, a negligible effect size is confirmed in all cases, significantly below the threshold of 0.2 typically used to denote small effects. These effect sizes reinforce the conclusion that the customization of the BSVP system has not resulted in significant improvements in student interaction compared to the standard ChatGPT-4 Turbo model. In my opinion, addressing these comments would significantly improve the quality of this research, enhancing its suitability for indexing. We sincerely appreciate the referee's comments."
}
]
},
{
"id": "317573",
"date": "04 Sep 2024",
"name": "María Beatriz Corchuelo Martínez-Azua",
"expertise": [
"Reviewer Expertise Economics",
"Teaching Innovation"
],
"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 the paper \"Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful?\". This research examines the effectiveness of generative language models, focusing on ChatGPT, in education. It compares ChatGPT with a customized assistant, the Business Statistics Virtual Professor (BSVP), designed for students at Universidad Pontificia Comillas. The study assesses the potential of these AI models to enhance learning, highlighting the need for effective personalization and fine-tuning. The findings reveal no significant differences between the two methods, suggesting that personalization may not be as impactful as anticipated. The study concludes that while personalized AI models hold promise, further research is needed to optimize their use in education. The following are some comments and suggestions that could enhance the overall impact of the research conducted: The work is presented clearly and precisely, with the study's methodology, results, and implications detailed effectively. The conclusions are well-supported by the results, and the study references relevant works, including previous studies and the context of the Spanish university system, which strengthens the evaluation criteria used in the research. However, the provided excerpts lack specific references to recent literature beyond the authors' previous work. To broaden the study's perspective, it would be beneficial to include references that discuss the use of language models in diverse educational contexts, both locally and internationally. This could offer a more comprehensive view of the applicability of the findings. The study commendably provides access to the source data underlying the results, with data availability on Figshare and appropriate licensing that supports transparency and reproducibility. However, the research's impact could be further enhanced by offering more detailed descriptions of the dataset, which would improve its usability for future research. While statistical results are presented, the study would benefit from a more in-depth discussion of their significance and practical implications. For instance, exploring how the results might affect educational practice or influence the adoption and use of virtual assistants in higher education would be valuable. Such an analysis could provide readers with a clearer understanding of the real-world applications and potential impact of the findings.\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate? Yes\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "12461",
"date": "23 Sep 2024",
"name": "Jose Luis Arroyo-Barrigüete",
"role": "Author Response",
"response": "We sincerely thank the reviewer for the time dedicated to evaluating our research. Below, we provide responses to her comments. The work is presented clearly and precisely, with the study's methodology, results, and implications detailed effectively. The conclusions are well-supported by the results, and the study references relevant works, including previous studies and the context of the Spanish university system, which strengthens the evaluation criteria used in the research. However, the provided excerpts lack specific references to recent literature beyond the authors' previous work. To broaden the study's perspective, it would be beneficial to include references that discuss the use of language models in diverse educational contexts, both locally and internationally. This could offer a more comprehensive view of the applicability of the findings. We sincerely appreciate your comment. Due to the space limitations required by the journal for a Brief Report, it is not possible to include a large number of new references or text. However, we have reviewed a significant number of papers on the subject and selected those that we believe provide relevant information for the present research. These have been included in the paper at the end of the “Related Work” section: Dong, B., Bai, J., Xu, T., & Zhou, Y. (2024, April). Large Language Models in Education: A Systematic Review. In 2024 6th International Conference on Computer Science and Technologies in Education (CSTE) (pp. 131-134). IEEE. Flores Limo, F. A.,... & Arias Gonzáles, J. L. (2023). Personalized tutoring: ChatGPT as a virtual tutor for personalized learning experiences. Przestrzeń Społeczna (Social Space), 23(1), 293-312. Laato, S., Morschheuser, B., Hamari, J., & Björne, J. (2023, July). AI-assisted learning with ChatGPT and large language models: Implications for higher education. In 2023 IEEE International Conference on Advanced Learning Technologies (ICALT) (pp. 226-230). IEEE. Salem, M., Shaalan, K. (2024). ChatGPT: Advancing Education with Virtual Assistants. In: Hassanien, A.E., Zheng, D., Zhao, Z., Fan, Z. (eds) Business Intelligence and Information Technology. BIIT 2023. Smart Innovation, Systems and Technologies, vol 394. Springer, Singapore. https://doi.org/10.1007/978-981-97-3980-6_25 Wang, K., Ramos, J., & Lawrence, R. (2023). ChatEd: a chatbot leveraging ChatGPT for an enhanced learning experience in higher education. arXiv preprint arXiv:2401.00052. Yigci, D., Eryilmaz, M., Yetisen, A. K., Tasoglu, S., & Ozcan, A. (2024). Large Language Model‐Based Chatbots in Higher Education. Advanced Intelligent Systems, 2400429. https://doi.org/10.1002/aisy.202400429 2. The study commendably provides access to the source data underlying the results, with data availability on Figshare and appropriate licensing that supports transparency and reproducibility. However, the research's impact could be further enhanced by offering more detailed descriptions of the dataset, which would improve its usability for future research. In order to offer more detailed descriptions of the dataset, we have uploaded a sample of the responses provided by both BSVP and ChatGPT-4 Turbo to a public repository. We have included the link to these files in the data availability statement: Figshare: Sample of provided responses: Real Customization or Just Marketing: Are Customized Versions of Generative AI Useful?, https://doi.org/10.6084/m9.figshare.26965354.v1 This document includes a sample of responses supplied by BSVP and ChatGPT-4 Turbo. While statistical results are presented, the study would benefit from a more in-depth discussion of their significance and practical implications. For instance, exploring how the results might affect educational practice or influence the adoption and use of virtual assistants in higher education would be valuable. Such an analysis could provide readers with a clearer understanding of the real-world applications and potential impact of the findings. After checking our document we definitely agree with this observation and feel very grateful with the reviewer to have told us to provide a wider discussion section. Please observe that we have augmented the discussion section regarding how the customized model can impact the students use of generative AI tools. In particular, we have focused our analysis in how does communication style conditions the student use of these models and how it also influences the fact that the customization has been done by a professor of the subject, clearly modifying the trust that the students feel with respect to the generative AI system once that they know that it is, somehow, validated and explored by the professors of the subject. Moreover, we have also given an argument on why, regarding statistics, the performance of the customized version does not clearly outperform the standard version, based on the fact that undergraduate statistics is a popular topic on the internet and it is knowledge accepted by all communities. We hypothesize that for another more subjective topics with different schools of thought, like for example different fields of philosophy like philosophy of mind, the personalized answers can outperform the standard answers as they will focus only on the school of thought being taught in the subject. Finally, in this discussion, we also provided some additional examples and references to support our arguments."
}
]
}
] | 1
|
https://f1000research.com/articles/13-791
|
https://f1000research.com/articles/13-191/v1
|
15 Mar 24
|
{
"type": "Review",
"title": "Clinical rationale for dietary lutein supplementation in post COVID-19 and mRNA vaccine injury syndromes",
"authors": [
"Anthony M Kyriakopoulos",
"Greg Nigh",
"Peter A McCullough",
"Stephanie Seneff",
"Anthony M Kyriakopoulos",
"Greg Nigh",
"Peter A McCullough"
],
"abstract": "Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. High dietary intake of lutein is beneficial against eye disease, improves cardiometabolic health, protects from neurodegenerative diseases, and is beneficial for liver, kidney, and respiratory health. Lutein protects against oxidative and nitrosative stress, both of which play a major role in post-COVID and mRNA vaccination injury syndromes. Lutein is an important natural agent for therapeutic use against oxidative and nitrosative stress in chronic illnesses such as cardiovascular and neurodegenerative diseases and cancer. It can also potentially inhibit spike protein-induced inflammation. Rich dietary supplementation of lutein, naturally derived in non-biodegradable Extra Virgin Olive Oil (EVOO), can most optimally be used against oxidative and nitrosative stress during post-COVID and mRNA vaccination injury syndromes. Due to its high oleic acid (OA) content, EVOO supports optimal absorption of dietary lutein. The main molecular pathways by which the SARS-CoV-2 spike protein induces pathology, nuclear factor kappa-light-chain-enhancer activated B cells (NF-κB) and activated protein (AP)-1, can be suppressed by lutein. Synergy with other natural compounds for spike protein detoxification is likely.",
"keywords": [
"Lutein",
"chronic illnesses",
"post-COVID and mRNA vaccination injury syndromes",
"inflammatory response",
"reactive oxygen species",
"extra virgin olive oil."
],
"content": "1. Introduction\n\nLutein is a fruit- and plant-derived xanthophyl-carotenoid with remarkable antioxidant properties.1 The daily dietary intake of lutein is considered of important medical value as it combats a wide range of pathologies including diseases of the eyes, nervous system, heart, skin, and many others.1–3 Moreover, an increased concentration of lutein in the blood is positively associated with a) increased respiratory function and b) decreased mortality from respiratory diseases.4 A recent study highlights the urgency of implementing biopharmaceutical-nutrient rich dietary components, including lutein, in order to improve immune function and enhance antiviral activity against SARS-CoV-2 infection.5 Another study focusing on the use of a carotenoid-rich diet against viral infections and disease remarkably reveals the need for lutein consumption as a non-provitamin A nutrient to combat the severe pathologic symptoms of COVID-19 (for full review see Ref. 6). However, although lutein is found abundantly in many consumable plants, including green vegetables, carrots, microalgae, and others, due to its low bioavailability, bio-accessibility and stability, these food sources are not adequate to provide the quantity needed to treat disease.7 One way to overcome the low lutein concentration obtained by diet, and, in order to achieve effective doses against disease, is the use of nutritional supplements containing lutein.\n\nHowever, the previous clinical studies focusing on the use of lutein supplementation against eye disease do not give clear results. Although high blood concentrations of lutein are achieved in the treated patients with eye disease, there are ambiguous therapeutic effects obtained from these studies. Therefore, the lutein-supplementation approach raises concerns about the efficacy of this nutrient for treating disease.8,9\n\nIn this review, we first investigate lutein’s health properties and the mechanisms of its activity. Furthermore, we analyze the antioxidant and anti-inflammatory role of rich food-based lutein intake in order to minimize oxidative stress and oxidant pathways induced by the spike protein in post-COVID10 and post mRNA vaccination associated diseases such as myopericarditis.11 Moreover, we investigate the optimum bioavailability of lutein in food combinations that can offer the best effective doses of lutein in order to treat these disorders. Nitrosative stress that accompanies oxidative stress is one of the primary targets of lutein.\n\nExtra virgin olive oil (EVOO), under preferable conditions of purification and storage, can provide a synergistic therapeutic effect and an optimum carrier for a lutein-enriched diet to treat post-COVID and mRNA vaccine injury syndromes. We conclude with a brief review of other naturally derived compounds that can act in synergy with lutein to decrease SARS-CoV-2 spike protein activity and can potentially provide a joint therapeutic effect in post-COVID and mRNA vaccination injuries.\n\n\n2. The therapeutic properties of lutein’s biologic activity against disease\n\nAmongst the 600 carotenoids that are beneficial for human health and the 20 carotenoids regularly detected in human blood, the tetraterpenoid-pigment, non-provitamin A, xanthophyl-lutein, has exceptional pharmacological activities. These activities are based on the compound’s remarkable antioxidant effects and enhanced properties for scavenging ROS. However, lutein’s abilities to treat disease go beyond the antioxidant and ROS scavenging properties and go far deeper into mechanisms of molecular pathogenesis and inhibition. Comprehensive pharmacological activities of lutein are described in the studies of Kim et al.12 and Algan et al.13 Amongst the most important therapeutic effects, summarized in Table 1, are the anti-cancer effects and protection against cardiac complications and neurodegeneration, in addition to immunomodulation effects and the inhibition of pro-inflammatory responses (produced by interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β) and chronic inflammation. These therapeutic effects are some of many that can prove useful for the treatment of post-COVID and mRNA vaccination injury syndromes.14,15\n\nSummarizing the literature evidence of lutein’s therapeutic effects presented in Table 1, the lipophilic, highly antioxidant molecule lutein exerts its activity on many organs of the body, including the brain, the heart, the kidneys, and the liver. Due to its structural properties (lutein is a dihydroxy carotenoid), the hydroxyl groups make lutein more hydrophilic than other xanthophylls (e.g., zeaxanthin) and increase its polarity in comparison to other carotenoids. It is therefore described in the literature that, due to the increased hydrophilicity and polarity, lutein can act more effectively than other carotenoids as a scavenger and neutralizer of ROS to more adequately prevent overwhelming damage in tissues.43\n\n\n3. Beyond the ROS scavenging properties of lutein. Relations to alleviations of SARS-CoV-2 spike protein-induced pathology\n\nApart from the enhanced scavenging properties of lutein, further studies show that this molecule exerts its anti-inflammatory activity by intervention in Toll-like receptor (TLR) signaling. Specifically, the Lin et al. study on broilers (in vivo and in vitro experiments) reveals that lutein exerts anti-inflammatory activity by reducing activity of the TRL4/myeloid-differentiation-factor 88 (MyD88) signaling pathway.44 The in vitro downregulation of TLR4/MyD88, combined with the reduction of TLR4 gene expression shown in vivo, explains why lutein produces an anti-inflammatory effect. This is by the reduction in expression and secretion of IL-1β and IL-6, and the increased expression and secretion of the anti-inflammatory cytokines IL-10 and Il-4. This study and several other studies also show downregulation of NF-κB signalling by lutein.33,37,44,45 Relevant to the pathogenesis caused by the SARS-CoV-2 spike protein, the upregulation of TLR4/MyD88 signalling is probably one of the key factors that induce excess inflammation through upregulation of IL-6, IL-1β and NF-κΒ.46,47 Moreover, the key phosphorylating pathways that are intensely activated through TLRs by the SARS-CoV-2 spike protein and are said to contribute substantially to the protease’s pathogenesis are p38 mitogen activated protein kinase (MAPK) and the c-Jun NH2-terminal kinase (JNK).48 p38 MAPK becomes activated by both TRL4 and TLR2 pathways.49\n\nWe have recently published a proposed approach to assist the human body in catabolism of the spike protein using three over-the-counter oral medications/supplements: nattokinase 2000 FU (100 mg) twice daily, bromelain 500 mg a day, and curcumin 500 mg twice a day. It is conceivable that serratiopeptidase and alkaline serine peptidase could also have a proteolytic effect on the spike protein. This base of detoxification therapy is proposed for 3-12 months or more while research continues and additional drugs are used clinically as indicated in each case. Addition of dietary lutein is very reasonable given the current state of knowledge in the field.50,51\n\nSpike protein, as well as its fragments released with detoxification, promote inflammation by stimulating the TLR2 and the TLR4 signaling pathways and hence the subsequent NF-κB response.46,52 End-stream of TLR4 and TLR2/p38 MAPK-dependent activation is the activation of the cAMP response element—binding protein (CREB).53 CREB in turn, when activated by p38 MAPK, regulates the gene expression of activated protein (AP)-1.54 AP-1 is a family of proteins and consists of transcription factor clusters implicated in inflammatory diseases,55 the development of neurodegenerative diseases,56 and in the development of cancer.57 Recently, our team has shown that SARS-CoV-2 spike protein, by stimulating the p38 MAPK dependent pathways, promotes the transcription of AP-1.48 The over-regulation of AP-1, however, can be lessened by lutein, according to in vitro studies.\n\nOh et al.58 investigated the role of lutein in suppressing the p38 MAPK and JNK pathways and concluded that lutein suppresses AP-1 activation and inflammatory processes through these pathways. The authors used LPS-induced macrophage and keratinocyte cellular systems to show that lutein suppressed the generation of IL-6 and production of cyclooxygenase 2 (COX2), a potent inflammatory and cancer-inducing enzyme, via both the interferon-γ (IFN-γ) and TNF-α pathways.59 In these experiments, lutein also suppressed the rising levels of matrix-metalloproteinase-9 (MMP-9). MMP-9 is a tissue remodelling protease, and increased activity is implicated in the progression of inflammatory disease (arthritis and diabetes), cardiovascular diseases (fibrosis, hypertension, and myocardial infarction), and cancer.60 In this regard, the activation of AP-1 and NF-κB constitute important factors regulating the transcription and translation of MMP-9.\n\nIn summary, lutein acts as a strong antioxidant – ROS scavenger agent and suppresses the p38/JNK-dependent activity of AP-1 transcription factors and pro-inflammatory cytokines, including MMP-9 and is well positioned as an adjunct dietary strategy to assist in base spike protein detoxification.\n\nFigure 1 illustrates the potential disease alleviating effects of lutein against the activation of p38 MAPK and JNK pathways and the related pathogenic responses induced by SARS-CoV-2 spike protein interactions.\n\n\n4. Lutein, oxidative stress, post-COVID syndrome, and mRNA vaccination injuries\n\nPost-COVID syndrome is a group of diseases occurring when the pathogenesis of SARS-CoV-2 and spike protein are manifested for a prolonged time after the resolution of infection.64 Apart from the regular symptomatology of COVID-19, manifested also in post-COVID syndrome (fatigue, headache, myalgia, etc.), the neurologic,65 psychiatric10 and cardiological66,67 complications of post-COVID syndrome, amongst many others (renal, respiratory, skeletal muscle, etc.),67 can be severe, requiring repurposing of drugs. One of the main mechanisms causing the disease manifestations in post-COVID syndrome is oxidative stress resulting in tissue damage, and the lowering of antioxidant defenses.10\n\nThe mRNA vaccines against COVID-19 can result in over-production of inflammatory cytokines that finally produce a multi-organ hyper-inflammatory response involving the cardiovascular system, the brain and the liver, as shown in human studies,68–71 amongst other pathologic findings found from in vivo and in vitro studies.72 Remarkable is the emergence of autoimmune and immune-mediated conditions after the mRNA vaccinations.11,71 Regarding the cardiological complications, Giannota et al. analyzed the role of oxidative stress in relation to the angiotensin/aldosterone hormonal axis which becomes upregulated by the circulating mRNA-expressed spike protein.73 Cases of pericarditis, associated with increased oxidative stress, can be attributed to the SARS-CoV-2 spike protein expressed by mRNA vaccination.11 In relation to oxidative stress, Table 2 provides a collection of representative studies, found by searching thoroughly in PubMed and ScienceDirect databases, that relate to post-COVID and mRNA injury syndromes. These studies predominantly highlight that both syndromes are related to the elevation of oxidative stress and thus to the weakening of antioxidant defenses. The findings of increased inflammatory responses are included in Table 2, as these are considered to be the result of excessive oxidative stress in the organism.\n\n* TOS, total oxidant status (mmol H2O2 Eq/L), TAS, total antioxidant status (mmol Trolox Eq/L).\n\nSummarizing the literature collection of studies presented in Table 2, both post-COVID and mRNA injury syndromes present with pathologic outcomes that are related to pro-oxidant/antioxidant (redox) imbalance.83 The redox homeostatic imbalance lowers the antioxidant defenses and causes excessive tissue damage. This can be lethal when the heart, the vasculature and the brain are affected.69,85 Oxidative stress influences the activation of the redox-sensitive pro-inflammatory pathways of NF-κΒ and AP-1, and the activity of their related transcription factors portends the outcome of the related pathologies. This is shown on a molecular and clinical level from previous studies on atherosclerosis.83,90,91 How the development of oxidative stress and the subsequent production of ROS detrimentally influence the development of redox imbalance and thus result in an arrhythmogenic heart is described in detail by the Dashwood.85 However, beyond ROS, there is also the issue of reactive nitrogen species (RNS) under conditions of oxidative stress.85 The activity of molecules involved in maintaining ROS and RNS homeostasis become imbalanced during oxidative stress conditions.\n\n\n5. The ROS and RNS imbalance during post-COVID and mRNA injury syndromes – The potential therapeutic role of lutein\n\nThe studies that have investigated the levels of NO a) in the serum of patients suffering from myopericarditis as a consequence of mRNA vaccination against SARS-CoV-2,76 and b) in the blood of patients suffering from myalgic encephalomyelitis and chronic fatigue syndrome as often encountered in post-COVID syndrome77,92 find that they deviate from normal values. The abnormal values of NO indicate a ROS and RNS imbalance producing oxidative and nitrosative stress. Therefore, the following subsections are dedicated to analysing the potential implications of ROS and RNS imbalance with respect to post-COVID and mRNA injury pathological developments. Moreover, lutein can potentially find its place in therapy as a diet-provided nutrient to normalise the pathologic levels of NO in post-COVID syndrome and mRNA vaccination induced injuries.\n\nThe mechanisms of ROS and RNS production involve a plethora of molecules and an interacting enzyme cascade. The ROS are predominantly produced by oxidase enzymes such as xanthine oxidase (XO) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) during mitochondrial oxidative metabolism.93,94 Moreover, superoxide dismutase (SOD) consumes superoxide anions (O2-) leaked from the electron chain to form hydrogen peroxide (H2O2). Peroxides in turn react with transition metals to produce hydroxyl radicals (OH.).\n\nFurthermore, XO produces electrons from purine degradation that contribute to H2O2 synthesis. NOX may also produce superoxide anions; however, both NOX and XO produce low levels of ROS in cardiac cells.85 RNS are produced by nitric oxide synthase (NOS). NOS, apart from nitric oxide (NO), also produces superoxide (O2-). NO and O2- can react with each other to produce the highly reactive product, peroxynitrite (ONOO-).94\n\nSurprisingly, low dose administration of peroxynitrite can act as a buffer molecule to prevent ventricular arrythmia. Experiments in animals have shown that intracoronary infusion of peroxynitrite suppressed ischemia and reperfusion (I/R)-induced ventricular arrhythmias.95 However, I/R induced ventricular arrhythmia suppression by peroxynitrite infusion was accompanied by an increase in nitrate/nitrite (NOx) metabolite levels and a decrease in endogenous superoxide production. Overall, these findings led to the conclusion that, due to the reduced superoxide production after the peroxynitrite infusion, there was adequate NO availability during the induced ischemia experiments that resulted in protection from ventricular arrythmia.\n\nThe normal production of NO by neuronal NOS (nNOS) and endothelial NOS (eNOS) is beneficial and leads to homeostasis in the neural system, including the brain96 and the cardiovascular system.97 An abnormal rise of NO in the organism, however, predominantly points to cytokine-mediated excessive release of NO by macrophages, and this is related to inflammatory disorders and excessive neurotransmission.98 Remarkable is the evidence of the pathogenic relationships between elevated levels of NO and autoimmune conditions such as rheumatoid arthritis99 and cognitive impairment and dementia.96 An excess of NO in the brain during oxidative stress, and hence excess of oxygen species generation, gives more chances for NO to produce peroxynitrite, which is highly linked to the pathogenic predisposition to Alzheimer’s disease (AD).100 Furthermore, the increased levels of NO create more chances for stroke episodes under conditions of extensive RNS-induced mitochondrial enzyme damage.101\n\nOn the other hand, unusually low concentrations of NO in the organism are a strong indicator for endothelium dysregulation and damage, for predisposition to severe cardiovascular disease, and other cardiovascular complications, if these are not already pathologically prevailing.97 During oxidative stress, low levels of NO predict that most of the NO synthesized by either eNOS or nNOS, or by inducible NOS (iNOS) (a special NOS induced under immune stimulation), is converted to peroxynitrite.\n\nThe catastrophic effects of the reduced levels of NO for the cardiovascular system are well known and include vasoconstriction, platelet aggregation, vascular endothelium damage, and enhancement of adhesion molecule (ICAM-1, VCAM, etc.) activity. These are fully documented by Raddino and colleagues.97 Furthermore, peroxynitrite accumulation leads to a further increase of ROS. An excess of peroxynitrite and ROS leads to the formation of S-nitrosoglutathione (GNSO) and oxidized glutathione (GSSG). The oxygen radicals and GSSG have a direct effect on cardiac ryanodine receptor type 2 (RyR2) activity to produce an arrhythmogenic phenotype that can eventually result in heart failure. The full description of how a ROS/RNS imbalance causes an arrhythmogenic phenotype is described in the study of Dashwood and coworkers.85 Briefly, the ROS/RNS imbalance and the reactivity of nitrogen and oxygen species produced out of this imbalance (accumulation of peroxynitrite, GSSG, H2O2, OH.), through their interaction with the RyR2 receptor found on the membranes of sarcoplasmic reticulum (SR), result in direct modifications of the protein’s tertiary structure by inducing disulfide bond formations, e.g., S-nitrosylations and S-glutathionylations on the RyR2 residues. The deformations on the RyR2 tertiary structure caused by the ROS/RNS imbalance are coupled with indirect effects on its structure, secondary to oxidation of Ca2+calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA). The activation of these enzymes ultimately results in the phosphorylation of RyR2 residues, the dissociation of the regulatory CaM ligand from RyR2, and to other alterations of the RyR2 protein structure. These structural changes culminate in the deregulation of intracellular Ca2+ gating in SR, otherwise controlled by RyR2 structural intactness. Due to these structural changes, the open probability (Po) of RyR2, which reflects the maintenance of the controlled release of Ca2+ in SR, becomes altered and increases. The overall physiologic effect is Ca2+ diastolic leak in SR, which leads to arrhythmogenic heart failure.\n\nThe arrhythmogenic cardiomyopathies (AC) are a group of heart diseases that can be the result of either genetic or acquired causations. Some of the main acquired causative factors that produce the AC phenotype are infectious myocarditis and toxicity-related cardiomyopathy. The most severe consequences of AC are ventricular ectopy, tachycardia, and unexplained sudden death.102 In the study of Schwab and coworkers,69 the cause of death after mRNA vaccination was attributed to acute arrhythmogenic cardiac failure that resulted from myocarditis. Although in this study, specific markers that evaluate the role of oxidative stress in relation to disease and sudden death were not included, reviewing the study of Dursun and colleagues11 can be enlightening in this respect. This study concludes that the levels of nitric oxide and oxidative stress index (OSI) are lower in the mRNA-related myopericarditis cases as compared with the acute-pericarditis cases. The OSI system employed by researchers in this study is a tool for the evaluation of the total oxidant status (TOS) over the total antioxidant status (TAS) in the organism.79,80 The assessment of OSI is based on the oxidative stress produced during acute ischemia/reperfusion (I/R) injury of the vasculature in animals. During the I/R-induced vascular tissue injury, the total concentrations of oxidant molecules (TOS), measured in mmol H2O2 Eq/Lt, become higher than normal. However, during vascular injury, the total concentration of antioxidant molecules (TAS), measured in mmol Eq/Lt, is much more enhanced than the elevation of TOS. This implies an overall drop of the OSI, a marker which is significant for the estimation of vascular tissue damage due to oxidative stress.79,80\n\nIt is thus possible that, in fatal myocarditis cases caused by mRNA vaccination,69 the arrhythmogenic cardiac failure was the result of excessive oxidative stress and therefore a ROS/RNS imbalance, as described by the research groups of Dashwood et al.85 and Protonotarios and colleagues.102 Moreover, the SARS-CoV-2 spike protein in its whole structure (trimer), is detected in the serum of patients developing myocarditis (accompanied with elevated levels of troponin) after mRNA vaccination, and not in the symptom-free vaccinated control cases.103 It can thus be assumed, again, that the toxicity inducing cardiomyopathy and causing the pro-oxidant/antioxidant imbalance in the organism, ultimately resulting in AC and death,69 is the spike protein expressed from mRNA vaccination. This conclusion is strongly supported by the study by Protonotarios A & colleagues.102\n\nIn this regard, the circulating levels of NO in the serum of the mRNA-injured patients are measured in low concentrations.11 However, the levels of NO measured in the serum of post-COVID patients suffering from myalgic encephalomyelitis and chronic fatigue syndrome are found in abnormally high concentrations, indicating nitrosative stress.77 Nevertheless, more studies are needed to look specifically at the role of nitrosative stress in these conditions in the post-COVID scenario.\n\nThe elevated levels of NO in the population of post-COVID patients can also be a contributing factor for cardiovascular disease. When the NO concentration is abnormally high in the blood and persists over time, especially in males, there is a higher risk of mortality from cardiovascular disorders.104 On a molecular level, during nitrosative stress, the NO conjugation with oxygen radicals and the subsequent process of peroxynitrite formation leads to the pathogenic nitrosylation of several compounds, including tyrosine residues in proteins to produce 3-nitrotyrosine (3-NT), and also nitrosylation of lipids and DNA.\n\nAccumulation of 3-NT eventually results in cellular death. The molecular relations of the processes of apoptosis, autophagy, pyroptosis, ferroptosis and the newly discovered process of parthanatos, with nitrosative stress and cell death due to 3-NT activity, are described in the study of Wang and colleagues.105 Eventually, the death of cells from nitrosative stress leads to a host of pathologic events, including myocardial hypertrophy and fibrosis, that lead to ischemia and heart failure. Furthermore, inflammation caused by NO,98 and the vascular damage to tissues other than the heart, lead to increased risk of neurological deficits of brain functions.96 It can thus be hypothesized, based upon the available evidence, that both conditions of abnormal NO levels in post-COVID syndrome (high NO) and mRNA vaccination injuries (low NO) are related to an overall ROS/RNS imbalance in the patients.\n\nEspecially vulnerable to SARS-CoV-2 spike protein are the human microglial cells. Clough et al. have shown that the spike protein, apart from producing extensive oxidative stress and an increase in hypoxia inducing factor (HIF1α) expression, also induces a 57% elevation in the expression of NOS in microglia. The authors note that nitrosative stress is one of the major contributors of spike protein-associated neuroinflammation and development of Neuro-COVID.106\n\n\n6. The nutritional supplementation of lutein can potentially alleviate the pathologic levels of NO found in post-COVID and mRNA injury syndromes\n\nNewborn infants provide possibly one of the best models to investigate the effects of a therapeutic agent on oxidative stress. Infants lack adult antioxidant defense mechanisms and therefore suffer from an excess of oxidative reactions due to an enhanced metabolic rate. Furthermore, human cells are unable to synthesize lutein. All these conditions have led investigators to measure precisely the effects of lutein on the alleviation of oxidative stress in infants. Studies on newborn infants have shown that the reduction of oxidative stress and balance of cellular redox potential can be achieved by lutein supplementation.107,108\n\nOther studies show that newborns also suffer from nitrosative stress complications due to oxidative stress reactions.109 It is therefore reasonable to assume that lutein can provide additional therapeutic benefits in infants due to the complementary balance of nitrosative stress and RNS that will result from the balance of oxidative stress produced by ROS.107,108 Furthermore, a specific study investigating the effects of ischemia/reperfusion-induced injury of retinal tissue indicates that the neuroprotective role of lutein results from balancing the RNS. The study shows clearly that lutein achieves an alleviation of oxidative damage and nitrosative stress concurrently. The study used the levels of nitrotyrosine as a marker to estimate the relief of nitrosative stress.110\n\nHaving the aforementioned studies in mind, the close relationship between oxidative stress and abnormal NO levels, shown in studies included in Table 2, which correlate NO with post-COVID encephalomyelitis10 and mRNA injury-related myopericarditis,11 indicate that lutein can be of therapeutic benefit for both conditions. Lutein can therefore be used as a regulatory molecule to equilibrate excess oxidative and nitrosative stress locally in harmed tissues and thereby normalize the NO levels in these conditions. This is likely specific to lutein because, in comparison to its structurally close homolog zeaxanthin and other xanthophyll carotenoids, lutein has a unique molecular configuration to achieve free radical scavenging with highest efficiency.111 The free radical species can also be RNS, and, as relevant studies show, lutein has the capacity to reduce by 50% the generation of NO produced during inflammation, while at the same time reducing mRNA expression and translation of iNOS by 75%.26,112 In addition to its beneficial impact on the redox status of NO, lutein also promotes expression of antioxidant enzymes such as heme-oxygenase-1 and NAD(P) H dehydrogenase (quinone-1).\n\nAs already discussed, lutein’s anti-inflammatory activity is mainly centralized on the reduction of NF-κB activity via the inhibition of p38 MAPK, JNK and Akt pathways. Specifically, for neural tissues, this has been convincingly shown in the Wu W & colleagues’ study.26 The researchers have used microglial cell lines to demonstrate that the anti-inflammatory and neuroprotective activity of lutein is exerted through the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) mediated NF-E2-related factor 2 (Nrf2) pathway. On the other hand, the neurotoxicity of SARS-CoV-2 spike protein is mainly exerted through the activation of p38 MAPK and JNK pathways that promote NF-κB activation and result in neurodegeneration.48\n\nTherefore, lutein can plausibly serve as a buffer molecule against excess oxidation and nitrosative stress and thereby potentially reduce or even eliminate the type of post-COVID and mRNA injury cases shown in Table 2. This effect may extend from attenuation of oxidative stress and in parallel restoration of levels of NO and reduction of other related toxic compounds produced during nitrosative stress.\n\nNeurotoxicity is induced by the spike protein.51 It is noteworthy here that lutein can buffer the potency and lower the p38 MAPK-related pathways that activate NF-kB, and thus prevent or even provide therapeutic effects on the conditions of dementia and neurodegeneration observed in post-COVID syndrome.10,81\n\nFigure 2 illustrates the plausible buffering and therefore potentially therapeutic activities of lutein that can be achieved by the equilibration of abnormal levels of NO in post-COVID syndrome and mRNA injury syndromes.\n\nFurthermore, the therapeutic effects of lutein on neurodegenerative disorders may go beyond the compound’s high antioxidant/anti-inflammatory activities. Recent experimental evidence demonstrates that lutein enhances the transfer of heme in microglial cells without causing iron accumulation and deposition. Normal heme and thus iron transport is beneficial for brain functions. It seems that lutein achieves this goal by inducing the expression of mitochondria iron transporter genes. As the authors of the relevant study conclude, the buffering effect of iron transport conferred by lutein may prove beneficial to counter the pathologic excessive iron deposition encountered in neurodegenerative disorders of AD, PD and sideroblastic anaemia.113 Finally, the downregulation of IL-6-dependent pro-inflammatory signalling by lutein may prove beneficial for the treatment of autoimmune disorders of the skin such as alopecia that occurs after mRNA vaccination,88,89 as well as other IL-6 related autoimmune and inflammatory disorders that may arise due to inflammatory cytokine upregulation.33,88,89,114\n\n\n7. Why lutein-rich food may be ideal\n\nThere is convincing evidence to suggest that a lutein-rich diet can be a valuable therapeutic intervention, either preventing onset of disease or alleviating disease symptoms. Amongst the carotenoids, the xanthophylls, and especially lutein (as mentioned previously) has unique structural properties that enable the molecule to perform enhanced scavenging of ROS and RNS (NO, peroxynitrite and N2O3).111,115 Moreover, during the inhibitory reactions with ROS and RNS, the energy obtained in lutein’s structure transforms the molecule to its triplet state. However, the lutein molecule has the capacity to release the energy gained as heat and return to its original ground state. In this regard, the regenerative capability of lutein makes it reusable for additional rounds of free radical species elimination, and, thus, its quantity and protective activity can be maintained over time in the tissues.116 Furthermore, the content in lutein of the retinal pigment, also called macular pigment (MP), is derived from dietary consumption.117 Relevant animal studies on primates reveal that the lutein content within MP correlates with the content found in the tissues of the brain,118 and therefore this may be the result of the accumulation of lutein from the diet in the organs. A relevant study that has investigated the content of lutein in the eyes of animals as a result of dietary supplementation corelates the antioxidant and anti-inflammatory effects of lutein against liver injury with the concentrations of lutein measured in the plasma and ophthalmic tissues.19 Moreover, increased plasma concentrations of lutein achieved by increased dietary intake are protective against primary development of atherosclerosis.119 Finally, when lutein is supplemented by intraperitoneal injections in animals and therefore travels by plasma to the renal tissues, it prevents kidney damage caused by ischemia/reperfusion injury.120\n\nOn average, as human studies on eye-related disease show, at least 6 mg/day of lutein should be consumed from food to achieve preventative or therapeutic results.121 Unfortunately, lutein has low bioavailability and bio-accessibility from food sources, and its stability depends on the food matrix and presence of other dietary components. The food processing (heat, pH etc) that degrades the structural stability of lutein makes its bioavailability even worse. Therefore, technical advances on microencapsulation are being developed to solve these problems.122 However, clinical studies on age-related macular degeneration (AMD) recommend that the consumption of food-based lutein is the best option, as the administration of supplements for AMD have given contradictory results.123 This may be because high-dose administration of a single xanthophyl-carotenoid like lutein has the effect of altering the plasma and other tissue concentrations of other xanthophylls such as zeaxanthin, and carotenoids such as β-carotene, which are also beneficial for the prevention of human disease.124,125 Given that the food-based consumption of lutein in western countries such as the USA is remarkably low (1.5 mg/day of lutein),126 other ways of improving human consumption of lutein should be investigated.\n\nRegarding the food matrix and other dietary components that affect its stability,122 the Lakshminarayana and colleagues animal study has found that olive oil (OO) is the optimum “carrier source” to achieve the best postprandial plasma concentrations of lutein that can reach the eyes.24 In this study, the absorption of lutein did not affect the content of other carotenoids in animals. However, the study of Lakshminarayana et al. does not prove that lutein supplements can be directly incorporated into OO. The researchers incorporated powdered C. benghalensis (vegetable) material into OO that enriched the OO up to 2.69 mg lutein per kg OO as a formulation to feed to animals.\n\nConsidering the aforementioned evidence, OO, and especially extra virgin olive oil (EVOO) can be an important source of bioavailable dietary lutein.127 Studies have shown that lutein loses a significant portion of its therapeutic value after several weeks of storage at room temperature. Montesano and colleagues, for example, showed that EVOO enriched with fruit-derived lutein underwent intensive auto-oxidation reactions over the 28 weeks of storage at room temperature.127 Although the EVOO mixture did not increase beyond the acceptable limits of peroxide value (PV) that characterize an EVOO (20 meq O2/Kgr oil),128 it had almost tripled its PV (>14 meq O2/Kgr oil) over that period of time. This rapid increase of PV predicts a reduction in its quality in terms of total polyphenols and intensive oxidation reactions carried out in the oil.129\n\nEVOO suffers from auto-oxidation reactions that degrade its valuable polyphenol content over time.130 In this regard, another methodology of EVOO purification has important implications for lutein preservation. According to the molecularly filtered method applied to EVOO,131 the content of lutein is preserved efficiently over a period of 24 months [Kyriakopoulos AM, personal communication and submitted for publication]. The purified EVOO produced from this method has been shown to be beneficial for the topical treatment of psoriasis in human subjects.131,132 In terms of post-COVID and mRNA injury cases, EVOO constituents (poly-unsaturated fatty acids and polyphenols) can also prove beneficial and act synergistically with lutein.\n\nRecent in silico studies predict that the two most valuable ingredients of EVOO, oleocanthal and oleuropein, can potentially inhibit the spike protein’s interaction with the ACE2 receptor. This inhibition has been demonstrated against the kappa, omicron and delta variants.133 Therefore, these essential polyphenols must also be conserved in EVOO during the intake of lutein. It is suggested that EVOO rich in lutein must be consumed raw without mixing with other foods during intake, as was done in the animal studies.24\n\n\n8. Synergy with other natural compounds against post-COVID and mRNA vaccination injuries\n\nACE2 binding by the spike protein RBD is the first step in virus infection, and therefore any agent that can disrupt this binding should have therapeutic value.134 The recently discovered molecular docking properties of lutein on spike protein’s interface with ACE2 receptors41 is therefore significant. To the extent that the SP/ACE2 interface is a key step in SP-associated pathologies, lutein’s strategic interference could help mitigate a wide range of post-COVID and mRNA vaccine injury sequelae.103,135\n\nIn this regard, a related in silico docking study41 points to lutein’s synergistic interaction with another phenolic compound, quercetin. The study predicts that, by binding to different spike protein structural locations, the combination of quercetin and lutein can enhance the destabilization of spike on the ACE2 interface. Moreover, it has been shown that quercetin exerts anti-COVID-19 activity by inhibiting the expression of ACE2 receptors.136 Curcumin, another highly lipophilic phytochemical, was shown in an in silico study to also have potentially inhibitory properties against the spike protein of the new SARS-CoV-2 variants.137 Curcumin can thus act synergistically with lutein. Quercetin, curcumin, and lutein all have anti-inflammatory properties that prompted this investigation into potential synergistic activities against post-COVID and mRNA vaccination injuries. Moreover, quercetin and curcumin have been considered as natural potential therapeutic agents against SARS-CoV-2 infection.136,138 In addition, bromelain, another naturally derived potent anti-inflammatory and proteolytic molecule, can be used synergistically with the aforementioned compounds to enhance the anti-inflammatory response.139 Finally, the fibrinolytic enzyme nattokinase can be used in conjunction with lutein, as it has recently been shown to effectively degrade the spike protein of SARS-CoV-2.140\n\n\n9. Conclusions\n\nAbundant evidence suggests that lutein could be an effective natural agent for use against chronic illnesses and post-COVID and mRNA injury syndromes. Due to the enhanced antioxidant properties of the molecule over the other xanthophylls and carotenoids, lutein can offer the most effective oxidation homeostatic balance, restore normal levels of NO, and alleviate ROS/RNS imbalance. Particularly in post-COVID and mRNA injuries, the levels of NO are altered, indicating nitrosative stress apart from oxidative stress. Although NO is not highly reactive, its derivatives generated with ROS reactions, such as peroxynitrate and N2O3, are highly reactive with larger biomolecules. Therefore, the impaired levels of NO can be a causative factor for arrhythmogenic cardiac failure. On these grounds, lutein’s adjuvant use for therapy has the potential to be lifesaving in these conditions. This is apart from lutein’s potential contribution to cardiovascular, kidney, liver, and neural-brain protection.\n\nFurthermore, lutein can be useful against conditions of cognitive failure and dementia occurring from chronic inflammation in post-COVID syndrome. Lutein’s antioxidant properties are complemented by its potential structural neutralization abilities against spike/ACE2 interactions. The spike protein is a long-lived circulating molecule in post-COVID syndrome, and it is detected in autopsy cases of mRNA vaccination-induced cardiovascular complications that result in death. Therefore, lutein’s complementary docking abilities on the spike protein interface to the ACE2 receptor make it a molecule of high interest for preventing these conditions. A lutein-rich dietary intake is preferred over a high dose supplement, based on the contradictory results from eye-disease clinical studies using supplements.\n\nEVOO can be the best carrier for intestinal absorption and accumulative dispersal of lutein in the tissues. In the way of natural supplementation, the competitive inhibition of other essential carotenoids (like β-carotene) absorption, accumulation, and activity can be avoided. Modern techniques on EVOO purification may naturally enhance the stability of derived lutein in EVOO. Complementarily, the valuable polyphenols and polyunsaturated fatty acids of EVOO can act synergistically with lutein to inhibit the spike protein and offer additional anti-inflammatory activities. Furthermore, lutein can be combined with the natural anti-inflammatory compounds such as curcumin, bromelain, quercetin and the proteolytic enzyme nattokinase to effectively inhibit the spike protein of SAR-CoV-2 and its variants from action. We conclude with a famous quote from Hippocrates: “Let food be thy medicine and medicine be thy food.” This may well be applicable in the case of lutein.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\n\nAcknowledgments\n\nSpecial thanks to Mrs. Trinity Brami for professionally creating the figures of this paper.\n\n\nReferences\n\nMitra S, Rauf A, Tareq AM, et al.: Potential health benefits of carotenoid lutein: An updated review. Food Chem. Toxicol. 2021; 154: 112328. PubMed Abstract | Publisher Full Text\n\nLeermakers ET, Darweesh SK, Baena CP, et al.: The effects of lutein on cardiometabolic health across the life course: a systematic review and meta-analysis. Am. J. Clin. Nutr. 2016; 103(2): 481–494. PubMed Abstract | Publisher Full Text\n\nGandla K, Babu AK, Unnisa A, et al.: Carotenoids: Role in neurodegenerative diseases remediation. Brain Sci. 2023; 13(3): 457. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMelo van Lent D, Leermakers ETM, Darweesh SKL, et al.: The effects of lutein on respiratory health across the life course: A systematic review. Clin. Nutr. ESPEN. 2016; 13: e1–e7. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nSims NR, Anderson MF: Mitochondrial contributions to tissue damage in stroke. Neurochem. Int. 2002; 40(6): 511–526. Publisher Full Text\n\nProtonotarios A, Elliott PM: Arrhythmogenic cardiomyopathy: A disease or merely a phenotype? Eur. Cardiol. 2020; 15: 1–5. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYonker LM, Swank Z, Bartsch YC, et al.: Circulating spike protein detected in post-COVID-19 mRNA vaccine myocarditis. Circulation. 2023; 147(11): 867–876. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGumanova NG, Deev AD, Kots AY, et al.: Elevated levels of serum nitrite and nitrate, NOx, are associated with increased total and cardiovascular mortality in an 8-year follow-up study. Eur. J. Clin. Investig. 2019; 49(3): e13061. Publisher Full Text\n\nWang F, Yuan Q, Chen F, et al.: Fundamental mechanisms of the cell death caused by nitrosative stress. Front. Cell Dev. Biol. 2021; 9: 742483. PubMed Abstract | Publisher Full Text | Free Full Text\n\nClough E, Inigo J, Chandra D, et al.: Mitochondrial dynamics in SARS-CoV2 spike protein treated human microglia: Implications for neuro-COVID. J. Neuroimmune Pharmacol. 2021; 16(4): 770–784. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPerrone S, Longini M, Marzocchi B, et al.: Effects of lutein on oxidative stress in the term newborn: a pilot study. Neonatology. 2010; 97(1): 36–40. PubMed Abstract | Publisher Full Text\n\nPerrone S, Tei M, Longini M, et al.: Lipid and protein oxidation in newborn infants after lutein administration. Oxidative Med. Cell. Longev. 2014; 2014: 781454. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKuligowski J, Vento M: Metabolomics, oxidative, and nitrosative stress in the perinatal period. Antioxidants (Basel). 2022; 11(7): 1357. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLi SY, Fu ZJ, Ma H, et al.: Effect of lutein on retinal neurons and oxidative stress in a model of acute retinal ischemia/reperfusion. Invest. Ophthalmol. Vis. Sci. 2009; 50(2): 836–843. Publisher Full Text\n\nRuban AV, Pascal A, Lee PJ, et al.: Molecular configuration of xanthophyll cycle carotenoids in photosystem II antenna complexes. J. Biol. Chem. 2002; 277(45): 42937–42942. PubMed Abstract | Publisher Full Text\n\nRafi MM, Shafaie Y: Dietary lutein modulates inducible nitric oxide synthase (iNOS) gene and protein expression in mouse macrophage cells (RAW 264.7). Mol. Nutr. Food Res. 2007; 51(3): 333–340. PubMed Abstract | Publisher Full Text\n\nPap R, Pandur E, Jánosa G, et al.: Lutein decreases inflammation and oxidative stress and prevents iron accumulation and lipid peroxidation at glutamate-induced neurotoxicity. Antioxidants (Basel). 2022; 11(11): 2269. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHirano T: Interleukin 6 in autoimmune and inflammatory diseases: a personal memoir. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 2010; 86(7): 717–730. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSindhu ER, Preethi KC, Kuttan R: Antioxidant activity of carotenoid lutein in vitro and in vivo. Indian J. Exp. Biol. 2010; 48(8): 843–848. PubMed Abstract\n\nKrinsky NI, Landrum JT, Bone RA: Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu. Rev. Nutr. 2003; 23: 171–201. Publisher Full Text\n\nAbdel-Aal E-SM, Akhtar H, Zaheer K, et al.: Dietary sources of lutein and zeaxanthin carotenoids and their role in eye health. Nutrients. 2013; 5(4): 1169–1185. PubMed Abstract | Publisher Full Text | Free Full Text\n\nVishwanathan R, Neuringer M, Snodderly DM, et al.: Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutr. Neurosci. 2013; 16(1): 21–29. 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PubMed Abstract | Publisher Full Text | Free Full Text\n\nMozaffarieh M, Sacu S, Wedrich A: The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence. Nutr. J. 2003; 2: 20. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWang Y, Roger Illingworth D, Connor SL, et al.: Competitive inhibition of carotenoid transport and tissue concentrations by high dose supplements of lutein, zeaxanthin and beta-carotene. Eur. J. Nutr. 2010; 49(6): 327–336. PubMed Abstract | Publisher Full Text\n\nBohn T, Desmarchelier C, El SN, et al.: β-Carotene in the human body: metabolic bioactivation pathways - from digestion to tissue distribution and excretion. Proc. Nutr. Soc. 2019; 78(1): 68–87. PubMed Abstract | Publisher Full Text\n\nJohnson EJ, Maras JE, Rasmussen HM, et al.: Intake of lutein and zeaxanthin differ with age, sex, and ethnicity. J. Am. Diet. Assoc. 2010; 110(9): 1357–1362. 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Physiol. 2023; 50(4): 267–276. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChakraborty AJ, Mitra S, Tallei TE, et al.: Bromelain a potential bioactive compound: A comprehensive overview from a pharmacological perspective. Life (Basel). 2021; 11(4): 317. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTanikawa T, Kiba Y, Yu J, et al.: Degradative effect of nattokinase on spike protein of SARS-CoV-2. Molecules. 2022; 27(17): 5405. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "288979",
"date": "01 Jul 2024",
"name": "Konstantinos Poulas",
"expertise": [
"Reviewer Expertise 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\nVery detailed and important manuscript by Kyriakopoulos et al, about the well established role of lutein as antioxidant and anti-inflammatory factor for a great number of pathologies.\nThe authors, apart from reviewing the current literature, are proposing the beneficial effect of lutein for post-COVID and post-vaccination health implications. I don't have any major comment. Knowing, however, that there is a debate about the existence or not of the so-called post-COVID syndrome, I would like the authors to include and discuss this debate in the manuscript, with the appropriate references.\nThey present, Figure 2, that post-COVID and post-vaccination pathologies are presenting different/controversial pathophysiological pathways. Since there is a strong possibility that post-COVID is a non-existent pathology, I would like the authors to modify the manuscript, wherever they present post-COVID pathophysiological characteristics in comparison with the post-vaccination pathophysiological pathways.\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": "12099",
"date": "06 Aug 2024",
"name": "Stephanie Seneff",
"role": "Author Response",
"response": "Response to Reviewer Comments We understand the reviewer’s concerns about post COVID and mRNA related injuries. Therefore, we have made the following changes to the manuscript. Since long COVID is a well-recognised syndrome, we have changed “post COVID (syndrome)” to “long COVID” throughout the text. We have inserted a new Section 2., explaining that long COVID and mRNA injury syndrome disease manifestations have a common origin. This is the SARS-CoV-2 spike protein induced pathology. Nowadays, most of the patients presenting with long term spike protein induced pathology are mRNA vaccinated, whereas in the unvaccinated population the long-term spike pathologies are more modest and infrequent. We address this issue by inserting a new reference: https://pubmed.ncbi.nlm.nih.gov/37634619/. In this study, it is quoted that long term COVID complications are more likely to emerge in the mRNA vaccinated individuals. In the group of individuals having a previous SARS CoV-2 infection (presumably not vaccinated) the risk factor for having long COVID complications does not increase. In Table 2, since most of the studies included are at the beginning of the COVID-19 pandemic, we assume that the patient results included are mainly from individuals who have not been vaccinated. Otherwise, the authors of these studies would have mentioned mRNA vaccination for the patients they investigated. In the conclusion section, we have inserted a specific sentence stating that long COVID and mRNA vaccination injury syndromes share the same origin of pathology, the SARS CoV-2 spike protein. Since the scope of this study is to investigate the potential therapeutic role of lutein against the SARS CoV-2 spike protein induced pathology, we consider that these above changes are enough to cover the scientifically well based reviewer comments."
}
]
}
] | 1
|
https://f1000research.com/articles/13-191
|
https://f1000research.com/articles/13-1243/v1
|
17 Oct 24
|
{
"type": "Software Tool Article",
"title": "A streamlined workflow for long-read DNA methylation analysis with NanoMethViz and Bioconductor",
"authors": [
"Shian Su",
"Lucinda Xiao",
"James Lancaster",
"Tamara Cameron",
"Kelsey Breslin",
"Peter F. Hickey",
"Marnie E. Blewitt",
"Quentin Gouil",
"Matthew E. Ritchie",
"Lucinda Xiao",
"James Lancaster",
"Tamara Cameron",
"Kelsey Breslin",
"Peter F. Hickey",
"Marnie E. Blewitt",
"Quentin Gouil"
],
"abstract": "Long-read sequencing technologies have transformed the field of epigenetics by enabling direct, single-base resolution detection of DNA modifications, such as methylation. This produces novel opportunities for studying the role of DNA methylation in gene regulation, imprinting, and disease. However, the unique characteristics of long-read data, including the modBAM format and extended read lengths, necessitate the development of specialised software tools for effective analysis. The NanoMethViz package provides a suite of tools for loading in long-read methylation data, visualising data at various data resolutions. It can convert the data for use with other Bioconductor software such as bsseq, DSS, dmrseq and edgeR to discover differentially methylated regions (DMRs). In this workflow article, we demonstrate the process of converting modBAM files into formats suitable for comprehensive downstream analysis. We leverage NanoMethViz to conduct an exploratory analysis, visually summarizing differences between samples, examining aggregate methylation profiles across gene and CpG islands, and investigating methylation patterns within specific regions at the single-read level. Additionally, we illustrate the use of dmrseq for identifying DMRs and show how to integrate these findings into gene-level visualization plots. Our analysis is applied to a triplicate dataset of haplotyped long-read methylation data from mouse neural stem cells, allowing us to visualize and compare the characteristics of the parental alleles on chromosome 7. By applying DMR analysis, we recover DMRs associated with known imprinted genes and visualise the methylation patterns of these genes summarised at single-read resolution. Through DMR analysis, we identify DMRs associated with known imprinted genes and visualize their methylation patterns at single-read resolution. This streamlined workflow is adaptable to common experimental designs and offers flexibility in the choice of upstream data sources and downstream statistical analysis tools.",
"keywords": [
"DNA methylation",
"Differential methylation",
"Long-read sequencing",
"Epigenetics",
"Bioconductor"
],
"content": "1. Introduction\n\nDNA methylation is a key epigenetic regulator of gene expression in mammals, involving the addition of a methyl group to cytosine or adenine nucleotides. In mammals, the predominant form of DNA methylation is 5-methylcytosine (5mC) in CpG dinucleotides. CpG methylation is involved in many important epigenetic processes, including differential gene expression, X-chromosome inactivation, genomic imprinting, and maintenance of genome stability.1 Changes in CpG methylation are implicated in a variety of different disease processes, including tumorigenesis and imprinting disorders such as Prader-Willi Syndrome and Angelman Syndrome.2\n\nOver the past couple of decades, multiple methods have been developed to measure DNA methylation, including bisulfite sequencing,3 methylation arrays,4 and more recently, third-generation sequencing technologies such as those offered by Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PacBio). While bisulfite sequencing has long been the gold standard for DNA methylation analysis, it suffers from several limitations; these include DNA degradation from the process of bisulfite conversion, incomplete conversion of unmethylated cytosines, amplification bias from PCR, and short read lengths that pose difficulties for assembly and haplotyping.5 By contrast, ONT’s nanopore sequencing and PacBio’s single-molecule real-time (SMRT) sequencing can directly sequence DNA molecules with all their modifications intact, and use basecalling algorithms to predict DNA modifications from the raw sequencing signal. Basecalling algorithms have the potential for bias, depending on the algorithm and training data used for the model; however, improvements are continually being made to generate more accurate models, and additionally, to detect other DNA modifications in other sequence contexts.6\n\nIn this workflow, we will demonstrate how to use the NanoMethViz package7 and other Bioconductor software to visualise and analyse methylation data generated by ONT long-read sequencing. The sequencing data is currently output in the modBAM file format, which contains the basecalled reads alongside tags for modification information. The NanoMethViz package provides a suite of tools for loading in this methylation data, visualising regional and genome-wide methylation patterns, and exporting data for identifying differentially methylated regions (DMRs) using other Bioconductor software such as bsseq,8 DSS,9 dmrseq10 and edgeR11.\n\n\n2. Methods\n\nIn this workflow, we will analyse ultra-long-read Nanopore sequencing data from the neural stem cells of triplicate E14.5 female mice from Gocuk and Lancaster et al., 2024.12 The mice were F1 crosses between an Xist knockout (XΔAX) female13 and a Castaneus strain (CAST) male. The resulting offspring have sufficiently different parental chromosomes to allow effective genome-wide haplotyping to distinguish the parent-of-origin for long-reads, allowing for the identification of genes that are imprinted or strain-specific. The Xist KO of the maternal genome also guarantees that X-inactivation takes place on the paternal X chromosome, allowing for the study of X-inactivation. The DNA was sequenced on R9.4.1 PromethION flow cells, basecalled with Dorado, aligned to the mm10 mouse reference genome, and phased with WhatsHap14 to produce the phased modBAM (Figure 1A). For illustrative purposes, we use a subset of the data focusing on chromosome 7, which contains several known imprinted genes.\n\n(A) Experimental setup for the data used in this workflow, from Gocuk and Lancaster et al., 2024. (B) Flowchart of the workflow for long-read methylation data visualisation and analysis using NanoMethViz and other Bioconductor packages including limma, dmrseq, bsseq, and edgeR. (C) Summary of data structures for the storage of methylation data used in different parts of the workflow. Xi: inactive X. Xa: active X. CAST: Castaneus. 5mC: 5-methylcytosine. MDS: multidimensional scaling. DMR: differentially methylated region. Figure created with BioRender.com.\n\nWe begin by loading the packages and downloading the input data which contains the modBAM files required for this workflow.\n\nAs mentioned, modBAM files are the currently preferred output of Dorado, the primary methylation caller offered by ONT. ModBAM files are BAM files containing reads with additional tags on each read storing information about methylation calls (the MM tag) alongside their methylation probabilities (the ML tag). To use this data in NanoMethViz, we must construct an object of the ModBamResults class.\n\nThe ModBamResults class is a container for storing methylation data from multiple samples, along with sample annotation and exon annotation. To create this object, we need to provide paths to the modBAM files, a sample table, and optionally exon annotation.\n\nThe samples need to be annotated with information for NanoMethViz to use in aggregating data within experimental groups. The sample table must contain sample and group columns with optional additional columns for further annotation. The rows of this table must match the order of the input files. The group column is generally the default grouping column used in the NanoMethViz package. In this example, we have grouped our data by haplotype.\n\nOptionally we can add exon annotation to the object to generate tracks for gene annotation when plotting genomic regions/genes. The exon annotation must be a data.frame with columns gene_id, chr, strand, start, end, transcript_id, and symbol. Several helper functions are provided to retrieve exon annotations in the correct format for human (hg19, hg38) and mouse (mm10, GRCm39). In this example, we will use the get_exons_mm10() function to retrieve exon annotations for the mouse genome (mm10) and filter for chromosome 7.\n\nOnce we have created the ModBamResult object, we can use the plot_gene() function to visualise the methylation patterns of a gene of interest. In this example, we will plot the methylation patterns of the Peg3 (paternally-expressed gene 3) gene on chromosome 7, which is known to be imprinted in mice. The plot contains a smoothed trendline of the group-aggregated methylation probabilities across the gene, along with a heatmap showing the methylation probabilities of individual CpG sites in each read, and a track showing the isoforms of the gene if exon annotation is provided (Figure 2).\n\nThis plot shows the methylation information along the Peg3 gene on chromosome 7. The top track shows a rolling-smoothed average of methylation probability across the region, aggregated across samples within each experimental group. The middle track shows a heatmap of the methylation probabilities within individual reads, separated by experimental group. The bottom track shows isoform annotations for Peg3, with rectangles representing exons, lines representing introns and arrows representing the direction of transcription.\n\nCpG dinucleotides are often enriched around gene promoters, where methylation is generally correlated with silencing and hypomethylation with activation. In the plot, we see that there is a strong demethylation pattern on the paternal allele near the transcription start site (TSS) of the gene, allowing the gene to be expressed. The maternal allele is hypermethylated near the TSS, silencing the gene. This is a typical methylation pattern for an imprinted gene, and consistent with paternal expression of Peg3.\n\nWhile it is possible to use modBAM files to analyse specific regions of interest, genome-wide analysis requires the data to be in a tabix-indexed TSV file as it is easier to parse at scale (Figure C). We can convert the modBAM files to a tabix-indexed TSV file using the modbam_to_tabix() function. This function will create a tabix-indexed TSV file containing the methylation data from the modBAM files. This file can then be used as input to the NanoMethViz functions that require sorted genomic data. In this example, we will convert the ModBamResult object to a tabix-indexed TSV file and save it to the data directory. We will use a pre-generated file in the interest of time, but you can run the code below to generate the file.\n\nOnce we have the tabix-indexed TSV file, we can create a NanoMethResult object using the NanoMethResult() function. The NanoMethResult object contains the same information as the ModBamResult object but with the methylation data stored in a tabix-indexed TSV file. To create this object we need to provide paths to the tabix-indexed TSV file, along with the accompanying sample table and exon annotation we generated before.\n\nThe NanoMethResult object behaves in the same way as ModBamResult for any plotting functions. For example we can use plot_gene() to visualise the methylation patterns of the Peg3 gene in exactly the same way but replacing the ModBamResult object with the NanoMethResult object. We should see the exact same plot as before.\n\nIt is often informative to aggregate methylation data over a class of features to identify broad patterns of methylation across the features. This can help establish overall differences in methylation patterns between groups in a class of features such as genes, CpG islands, or enhancers. The NanoMethViz package provides a plot_agg_regions() function for visualising methylation data that has been aggregated across a set of genomic regions of interest, defined by a table of coordinates.\n\nFor example, we may want to investigate the methylation patterns of a set of genes on chromosome 7. We can use the exons_to_genes() helper function to convert exon annotations already stored in the object to gene annotations and filter for only chromosome 7 genes (Figure 3). For faster processing, we subset 200 genes and use the plot_agg_regions() function to visualise the mean methylation proportions along the sampled genes. By default, the methylation proportion is calculated using a threshold of 0.5 modification probability.\n\nThe mean methylation proportion is shown across a sample of 200 genes in chromosome 7, aggregated by experimental group. Methylation proportions are individual CpG sites are calculated along relative genomic positions, with fixed flanking regions, then averaged across all genes in each experimental group to produce a smoothed trendline. The x-axis label gives the average width and standard deviation of widths of the features used.\n\nIn this plot we can see that active genes on chromosome 7 tend to be demethylated near the TSS region and hypermethylated throughout the gene body. This is consistent with the proposed function of methylation in gene regulation, where methylation in promoter region of genes is associated with gene silencing, while transcription of active genes is associated with recruitment of methylating mechanisms to the gene body.\n\nAnother class of features of interest are CpG islands, which are regions of the genome that are rich in CpG dinucleotides. CpG islands are often associated with gene promoters and are predominantly unmethylated in normal cells.15 We can use the get_cgi_mm10() function to retrieve CpG island annotations for the mouse genome (mm10) and filter for chromosome 7. We can then use the plot_agg_regions() function to visualise the mean methylation profile across CpG islands on chromosome 7 (Figure 4).\n\nThe mean methylation proportion is shown across CpG islands on chromosome 7, aggregated by experimental group. Methylation proportions are individual CpG sites are calculated along relative genomic positions, with fixed flanking regions, then averaged across all CpG islands in each experimental group to produce a smoothed trendline.\n\nAs expected, we see a clear pattern of demethylation over CpG islands on chromosome 7, relative to neighbouring genomic regions.\n\nNanoMethViz is primarily designed for visualising methylation data. In order to perform differential methylation analysis, we can use other Bioconductor packages that implement sophisticated statistical procedures, such as dmrseq. The dmrseq() function requires a BSseq object as input, so we convert the NanoMethResult object to a BSseq object using the methy_to_bsseq() function.\n\nWe remove any sites that are zero in every samples of either experimental group; these low coverage regions are generally not informative for differential methylation analysis. The BSseq object stores the methylation data as two matrices, the methylation matrix and the coverage matrix (Figure 1C), with the option to store additional information such as sample annotation and genomic regions.\n\nThis conversion process usually takes some time, so we will load a pre-generated BSseq object. The code used to generate the object is provided below.\n\nUsing the BSseq object, we can create a multi-dimensional scaling (MDS) plot to visualise the relative differences in methylation between the samples, a method commonly used in differential gene expression analysis. The MDS function within NanoMethViz uses the plotMDS() function from limma.16 Since BSseq objects store the methylation data as two matrices, the methylation matrix and the coverage matrix, we need to convert the BSseq object such that each CpG site from each sample is represented by a single value in a matrix. This can be done using the bsseq_to_log_methy_ratio() function, which converts the BSseq object to a matrix of the log of the methylation ratio with a small count added to prevent division by zero.\n\nThe plot_mds() function can then be used to create an MDS plot of the samples using the log methylation ratio matrix as input. The samples are coloured by group – in this case, maternal and paternal.\n\nBecause the number of CpG sites is large, here we aggregate the methylation data over CpG islands to both reduce the size of the data and produce a more stable measure of methylation. This is done by providing the regions = cgi_anno argument to bsseq_to_log_methy_ratio(). Without the argument, the function will use individual CpG sites. After the data is aggregated, plot_mds() uses only the top 500 most variable features to create the MDS plot (Figure 5).\n\nThe multi-dimensional plot is created based on the top 500 most variable genes in on chromosome 7 in terms of log-methylation-ratio over the gene bodies. The samples are coloured by group, and distances between samples is reflective of the difference in the methylation profile across genes in each sample.\n\nFrom this MDS, we see that there is clear separation between the maternal and paternal groups based on CpG islands on chromosome 7, suggesting that the most variable CpG islands are differentially methylated between the two groups. Given that this is autosomal data, the separation is likely due to imprinting or strain-specific effects. We therefore expect to find some differentially methylated regions between the maternal and paternal groups.\n\nAnother common analysis is to identify differentially methylated regions (DMRs) between experimental groups. It is often informative to identify DMRs rather than just single differentially-methylated CpG sites, as these may correspond to gene regulatory regions such as promoters, silencers and enhancers, and have biological relevance for differential epigenetic regulation. However, DMRs are not easy to identify, as DMR calling requires the identification of individual significant sites, some determination of whether nearby sites should be aggregated into a region, and a statistical test to determine if the region as a whole is differentially methylated.\n\nThe dmrseq package can be used to identify DMRs between the two groups in our data. The dmrseq() function from the package requires a BSseq object as input, along with the name of the covariate to test for differential methylation. We will test for differential methylation between the maternal and paternal groups. The dmrseq() function returns a GRanges object containing the DMRs identified by the function. The GRanges object contains the genomic coordinates of the DMRs, along with information about the statistical significance of the DMRs.\n\nThere are alternatives to dmrseq for identifying DMRs, such as bsseq, DSS and edgeR. For bsseq and DSS, the same BSseq object can be used as input, while edgeR requires a DGEList object as input (Figure 1C). The DGEList object can be created from the BSseq object using the bsseq_to_edger() function, or from the NanoMethResult object using the methy_to_edger() function (Figure 1B).\n\nbsseq, DSS and dmrseq all use a similar approach to identify DMRs: first, they use a statistical test to compare the methylation levels between the two groups at each CpG site, followed by a clustering step to identify regions of the genome with consistent differences in methylation levels for de novo DMR discovery. On the other hand, edgeR requires users to choose the regions to test for differential methylation, which is reflected by the regions over which they choose to summarise counts, and therefore cannot be used for de novo DMR discovery. dmrseq and edgeR produce p-values for each region, while bsseq and DSS only provide p-values for each CpG site along with an aggregated area statistic.\n\nA number of regions will be produced by dmrseq, including regions that were aggregated because they contained significant CpG sites but subsequently failed to reach statistical significance at a region level. It is difficult to directly interpret the regions returned by differential methylation analysis, and we commonly wish to identify these regions are possible control regions for genes. We do this by associating DMRs with genes using proximity to the gene transcription start site (TSS), first by constructing an annotation of a promoter region, then overlapping it with the DMRs. We use a liberal window of 10kb around the TSS to capture potential promoter regions, this is done by transforming the gene annotation to a GRanges object, then using the promoters() function from IRanges17 to define the promoter region as 5kb upstream and 5kb downstream of the TSS. We then use the join_overlap_intersect() function from plyranges to find the DMRs that overlap with the gene TSS regions. This will return a GRanges object containing the regions where DMRs which overlap with the promoter region, and the associated gene in that region.\n\nAfter we identify the DMRs that overlap with the gene TSS regions, we can filter for the significant DMRs using the qval column. This is the adjusted p-value for the DMRs, calculated using the Benjamini-Hochberg procedure to control false-discovery rates for multiple-testing. We can then select the columns we are interested in, such as the gene symbol, chromosome, start and end positions of the DMRs, the strand of the gene, and the q-value of the DMRs.\n\nWe now have a list of DMRs which overlap the TSS of genes on chromosome 7 and have a q-value < 0.05. The genes on this list are all known imprinted genes in the mouse, including Peg3, which we plotted in the first section of this workflow. We can plot the methylations of these genes and highlight the DMRs by setting the plot_gene() function’s anno_regions argument to the regions identified. This will highlight the significant regions in the gene plot in a shaded band. Here we will plot Peg3, Kcnq1ot1, and Cdkn1c (Figure 6). We can see that for all three of these genes, as required by our filtering criteria, the differentially methylated regions fall near the TSS.\n\nThe plots show the genes Peg3, Kcnq1ot1, and Cdkn1c along with green highlighted region denoting the DMR discovered by dmrseq.\n\nWe can see that the DMR for Cdkn1c extends beyond the region that is plotted when we use plot_gene(). We can plot these DMRs using plot_region(), with 2000 bases of flanking sequence added to both sides of the DMR to better visualise the full scope of the differentially methylated region (Figure 7).\n\nThis plot shows a more expanded region around the gene Cdkn1c to show the full DMR.\n\nWe have now successfully used dmrseq to statistically identify differentially methylated regions around known imprinted genes. Additionally, we have used that information to visualise the methylation data of the genes associated with the DMRs, and identify maternal- and paternal-specific methylation of the TSS.\n\n\n3. Summary\n\nIn this workflow, we have demonstrated a complete end-to-end pipeline for analysing and visualising methylation data generated by ONT long-read sequencing using NanoMethViz, dmrseq and other Bioconductor packages. We have shown how to preprocess the data, load it into NanoMethViz, visualise the methylation patterns of genes and aggregated features, cluster samples using MDS plots, and identify DMRs between experimental groups. We have also shown how to associate DMRs with genes and visualise the methylation patterns of genes associated with DMRs. While the DMRs identified in this tutorial were all associated with known imprinted genes, this workflow could be used in other experimental contexts to identify candidate genes involved in disease pathogenesis, or discover new gene regulatory elements. Further analysis could include enrichment analysis of the differentially-methylated genes, to bring out pathways that may be up- or downregulated in different processes. Ultimately, this workflow demonstrates a toolkit for the exploration and analysis of methylation data from long-read sequencing, which can be applied to a range of resolution levels and biological contexts. While the workflow demonstrates analysis of 5mC data from the ONT platform, it can also be applied to other long-read DNA methylation data such as that produced by PacBio SMRT sequencing, or other modification types such as 5hmC or 6mA, as well as potentially RNA modifications, provided that data is made available in modBAM format.\n\n\n4. Implementation\n\nThis workflow makes use of various open-source R packages available from the R18 and Bioconductor19 projects, with version numbers shown below.\n\nUsing the provided example data, this workflow can be run with 16GB of RAM and 3GB of disk space on a computer with R v4.4.0, Bioconductor v3.19 and the developmental version of NanoMethViz v3.1.5 installed.\n\n\nAuthor contributions\n\nS.S., L.X. and J.L. developed the workflow, performed data analysis, generated figures and wrote the manuscript and T.C., K.B. and M.E.B. generated data analysed in the workflow. P.F.H., M.E.B., Q.G. and M.E.R. supervised the project and wrote the manuscript. All authors read and approved the final manuscript.",
"appendix": "Data availability\n\nData files obtained from Gocuk and Lancaster et al. 2024 12 that were used in this workflow are available from:\n\nZenodo: Long-read methylation data analysis with NanoMethViz and Bioconductor, DOI: 10.5281/zenodo.12747550.\n\nFile: input.tar.gz contains modBAM (aligned to mm10, split into haplotypes and subset to chromosome 7) and sample annotation information.\n\nLicense: CC0.\n\n\nAcknowledgements\n\nWe thank Kathleen Zeglinski for creating the NanoMethViz logo and members of the Epigenetics and Development Division at WEHI for their feedback on this workflow.\n\n\nReferences\n\nJin B, Li Y, Robertson KD: DNA Methylation: Superior or Subordinate in the Epigenetic Hierarchy? Genes Cancer. 2011 Jun; 2(6): 607–617. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRobertson KD: DNA methylation and human disease. Nat. Rev. Genet. 2005 Aug; 6(8): 597–610. Publisher Full Text\n\nFrommer M, McDonald LE, Millar DS, et al.: A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. Proc. Natl. Acad. Sci. USA. 1992 Mar; 89(5): 1827–1831. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPidsley R, Zotenko E, Peters TJ, et al.: Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling. Genome Biol. 2016 Oct; 17(1): 208. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGouil Q, Keniry A: Latest techniques to study DNA methylation. Essays Biochem. 2019 Dec; 63(6): 639–648. PubMed Abstract | Publisher Full Text\n\nLiu H, Zhou J, Tian W, et al.: DNA methylation atlas of the mouse brain at single-cell resolution. Nature. 2021 Oct; 598(7879): 120–128. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSu S, Gouil Q, Blewitt ME, et al.: NanoMethViz: An R/Bioconductor package for visualizing long-read methylation data. PLoS Comput. Biol. 2021 Oct; 17(10): e1009524. PubMed Abstract | Publisher Full Text | Free Full Text\n\nHansen KD, Langmead B, Irizarry RA: BSmooth: From whole genome bisulfite sequencing reads to differentially methylated regions. Genome Biol. 2012 Oct; 13(10): R83. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPark Y, Wu H: Differential methylation analysis for BS-seq data under general experimental design. Bioinformatics. 2016 May; 32(10): 1446–1453. PubMed Abstract | Publisher Full Text\n\nKorthauer K, Chakraborty S, Benjamini Y, et al.: Detection and accurate false discovery rate control of differentially methylated regions from whole genome bisulfite sequencing. Biostatistics (Oxford, England). 2019 Jul; 20(3): 367–383. PubMed Abstract | Publisher Full Text | Free Full Text\n\nChen Y, Pal B, Visvader JE, et al.: Differential methylation analysis of reduced representation bisulfite sequencing experiments using edgeR. F1000Res. 2018 Oct; 6: 2055. PubMed Abstract | Publisher Full Text | Free Full Text\n\nGocuk SA, Lancaster J, Su S, et al.: Measuring X inactivation skew for retinal diseases with adaptive nanopore sequencing. Genome Res. 2024 Sep; gr.279396.124. In press. PubMed Abstract | Publisher Full Text\n\nRoyce-Tolland ME, Andersen AA, Koyfman HR, et al.: The A-repeat links ASF/SF2-dependent Xist RNA processing with random choice during X inactivation. Nat. Struct. Mol. Biol. 2010 Aug; 17(8): 948–954. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartin M, Patterson M, Garg S, et al.: WhatsHap: Fast and accurate read-based phasing. bioRxiv. 2016 Nov. Publisher Full Text\n\nDeaton AM, Bird A: CpG islands and the regulation of transcription. Genes Dev. 2011 May; 25(10): 1010–1022. PubMed Abstract | Publisher Full Text | Free Full Text\n\nRitchie ME, Phipson B, Wu D, et al.: Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015 Apr; 43(7): e47. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLawrence M, Huber W, Pagès H, et al.: Software for Computing and Annotating Genomic Ranges. PLoS Comput. Biol. 2013 Aug; 9(8): e1003118. PubMed Abstract | Publisher Full Text | Free Full Text\n\nR Core Team: R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2024.\n\nHuber W, Carey VJ, Gentleman R, et al.: Orchestrating high-throughput genomic analysis with Bioconductor. Nat. Methods. 2015; 12(2): 115–121. PubMed Abstract | Publisher Full Text | Free Full Text"
}
|
[
{
"id": "338940",
"date": "20 Dec 2024",
"name": "Keegan Korthauer",
"expertise": [
"Reviewer Expertise Statistical genomics"
],
"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 details a workflow for analyzing long-read DNA methylation analysis using the Bioconductor package NanoMethViz and additional Bioconductor packages. The article illustrates the main functionality of this software and companion tools using a small subset of a published ONT study of murine imprinting, including: data import, plotting modification probabilities in local annotated regions, summarizing methylation proportions across genomic region sets, and converting to methylated and unmethylated read counts to take advantage of other Bioconductor tools to construct multidimensional scaling plots and visualize differentially methylated regions.\nThe workflow centers on the NanoMethViz software, which is has already been detailed in a PLOS Computational Biology article from 20211. However, this workflow provides advances in (1) providing a detailed vignette using a real-world example, and (2) illustrates several extensions that allow for seamless integration of complementary tools for analysis of DNA methylation data. I feel the article would be strengthened by explicitly highlighting the advances made to the software since its release (e.g. supporting updated file types, adding conversion functions), as this type of work is too often devalued even though it is just as important to scientific progress as developing brand new tools. I have also detailed minor comments below.\nMinor comments:\nThe NanoMethViz package and workflow take as input the modBAM files currently output by ONT long-read sequencing processing software Dorado. It may be helpful to the reader to indicate whether other software currently output this file format (including ONT tools as well as PacBio tools). Does NanoMethViz also provide functionality for output of any other format to facilitate reanalysis of prior studies or integrative analysis? Or are there tools to convert alternate/legacy file formats to modBAM? Although not necessary to offer this functionality, it may be helpful to the reader to know whether this is possible. In the overview of DNA methylation measurement technologies in the introduction, when discussing the limitations of bisulfite sequencing, Enzymatic Methyl sequencing (EM-seq) should also be mentioned as alternative short-read sequencing approach. Suggest to write out the default y-axis label in plots like the top panel of Figure 2 as “Modification probability” or “Mod probability” for clarity. Please clarify the meaning of the thin grey bar in middle panel of Figure 2 – presumably this delineates the existence of a read, but either no CpG present or no methylation probability estimate? It is not clear what the tiny pink and blue shapes represent in bottom panel of Figure 2. The text references a “Figure C” – is this referring to Figure 1C? The utility of the tabix file was not immediately clear to me on first read of the first paragraph of section 2.3 – the addition of a sentence that explicitly states that the tabix file contains the read-level modification probabilities across all sites for all samples (or modified to correct my understanding as necessary) may be helpful. It’s not clear how the methylation proportions as displayed in Figure 3 are calculated. Is this the proportion of samples in each group that had an average modification probability of 0.5 or higher at that CpG, averaged over all samples? Figure 3 is interpreted as “In this plot we can see that active genes on chromosome 7 tend to be demethylated near the TSS region and hypermethylated throughout the gene body.” However, I understand it to be a plot of 200 randomly selected genes. As a result, I expect that some of the 200 genes are active but some are not.\n\nWhat assumptions are made when converting a NanoMethResult object to a BSseq object (e.g. methylated if greater than 0.5 probability)? Can this be changed by the user? The article mentions alternatives to dmrseq that, like dmrseq, were also developed for short-read sequencing data. However, there are alternatives for DMR detection that were developed specifically for ONT long-read sequencing (e.g. Snajder et al 20232) that would be helpful to mention.\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? Yes\n\nAre the conclusions about the tool and its performance adequately supported by the findings presented in the article? Yes",
"responses": []
},
{
"id": "338943",
"date": "09 Jan 2025",
"name": "Tim Triche Jr",
"expertise": [
"Reviewer Expertise bioinformatics",
"epigenetics",
"loss of imprinting"
],
"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 and workflow is excellent\nContrasting Figure 3 and Figure 5, we see that parent of origin (allelic) methylation analysis is critically important for imprinted regions like PEG3. HOWEVER, the authors state that we can see a clear separation for all three replicates along allelic axes. This does not actually appear to be the case -- nsc_3 maternal and paternal are nearly indistinguishable. Searching through the text provides no further remarks on why this is so. For the sake of clarity, it would be highly desirable to discuss the result and its interpretation.\n\ndmrseq is great, but it can take a while. It would be ideal to provide users with some idea of what to expect in terms of timing, e.g. by using system.time() for steps that are compute intensive.\n\nBSseq conversion is an issue which deserves a separate article/workflow/discussion on how it could be optimized. Warning the reader is appreciated!\nWith minor edits this is a superb manuscript.\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/13-1243
|
https://f1000research.com/articles/13-997/v1
|
02 Sep 24
|
{
"type": "Research Article",
"title": "A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units",
"authors": [
"Sridevi H.B.",
"Anisha Maria Fernandes",
"Sanyo D'souza",
"Prashantha B.",
"Pooja Rao",
"Suchitra Shenoy M",
"Sridevi H.B.",
"Sanyo D'souza",
"Prashantha B.",
"Pooja Rao",
"Suchitra Shenoy M"
],
"abstract": "Introduction Cancer and cytotoxic chemotherapy used for its treatment predispose to severe and often fatal infections. Prompt diagnosis and timely antibiotic therapy are crucial, with delays in therapy initiation having high mortality. Complete blood count (CBC) is an inexpensive, standardized, and preliminary investigation for the management and follow-up of cancer patients with diagnostic and prognostic value.\n\nMethod We studied the types of infections associated with various cancers treated with chemotherapy, their etiologies and susceptibility patterns, and the hematological profile of these patients as predictors of infection.\n\nResults A total of 21 patients (12 solid and 9 hematological malignancies) presented with 31 febrile episodes. White Blood cell count (2079 cells/cu. mm), percentage of neutrophils (52.9%), absolute neutrophil (137.5 cells/cu. mm), and platelet count (1,77,507 cells/cu. mm) were significantly lower in the 11 patients with febrile neutropenia. The absolute lymphocyte count (412.7 cells/cu. mm) was reduced with a strikingly low Neutrophil-to-lymphocyte ratio (NLR) (6.07) in patients with neutropenia. Laboratory and radiological evidence were present in 14/15 episodes of hematological malignancies (p-0.218) whereas unexplained clinical sepsis was common in solid malignancies (p-0.0202). The majority of documented infections were bacterial, caused by gram-negative bacilli, often showing multi-drug resistance. Infectious etiologies were identified in 71.4% of the patients with febrile neutropenia for >5days. Bacterial infections developed within 2 days of neutropenia, whereas viral and fungal infections manifested in prolonged neutropenia. Multi-site infections and higher mortality rates were observed in patients with febrile neutropenia. (p<0.04)\n\nConclusion Febrile neutropenia is a common complication among patients receiving chemotherapy for cancer, with an increased risk of morbidity and mortality. Early, rapid, and accurate diagnosis is key to prompt intervention. Hematological parameters such as Total Leukocyte count, platelet count, NLR, and Platelet-to-lymphocyte ratio are promising biomarkers in conjunction with morphological changes in neutrophils, thus proving that CBC and peripheral smears are simple, easily available, cost-effective, and highly dependable screening tools, especially in resource-poor settings.",
"keywords": [
"Oncology",
"Complete Blood Counts (CBC)",
"Diagnostic stewardship",
"infections"
],
"content": "Introduction\n\nBetter outcomes in cancer patients are seen with advancements in management using more aggressive and tailored regimens. Infections, however, continue to be a major cause of morbidity and mortality in cancer patients.1 Immunosuppression due to malignancy as well as therapeutic modalities increase an individual’s susceptibility to infections. In hematological malignancies, the underlying immune deficiencies and myelosuppressive treatments are major contributing factors.4 Obstruction, disruption of anatomical barriers and surgical interventions are additional risk factors for infections in solid tumours.5 Apart from cytotoxic chemotherapy, radiotherapy and the use of medical devices such as catheter, stents and prosthesis carry an increased risk.5\n\nCommon sites of infection are the blood stream, urinary tract, respiratory tract, and skin and soft tissue. Severe and persistent neutropenia, especially absolute neutrophil counts (ANC) <100 cells/ml, exponentially increases the risk of severe infections with bacterial, fungal, viral, and parasitic agents.4,5 Bacterial infections are the most common and are often polymicrobial.4,5 Studies from India, including one from our own center, show that infections are predominantly due to gram-negative bacilli. The increased incidence of multidrug-resistant organisms complicates its management.3,6–8\n\nA complete blood count (CBC) with peripheral smear examination is an important tool for monitoring patients undergoing chemotherapy. White blood cell (WBC) analysis is commonly used to investigate the risk of infection; however, in patients undergoing chemotherapy, it becomes challenging as the total WBC count is low and neutropenia may be observed. Infections stimulate the production of cytokines which in turn stimulates the production of immature granulocytes from marrow and this can be evidenced as ‘left shift’ in the smear examination. Toxicity changes in neutrophils in the form of toxic granules and vacuoles are observed in patients with infection. Absolute leukocyte counts, such as absolute neutrophil count, absolute monocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet parameters such as plateletcrit (PCT), platelet distribution width (PDW), and mean platelet volume (MPV), have been extensively studied in predicting infections.9–11\n\nIncreased mortality rates are observed when initial therapy with inappropriate antibiotics is initiated, even if the regimen is adjusted later based on microbiological investigations.2 Early diagnosis with prompt and appropriate antibiotics ensures favorable outcomes. A robust diagnostic and antimicrobial stewardship program could guide oncologists and physicians in timely and effective empirical therapy.\n\nOur study aimed to study the types of infections in patients with cancer undergoing chemotherapy, to identify the association of infections with specific cancers, the etiological agents, and their antimicrobial susceptibility profile, and to study the hematological profile of patients receiving chemotherapy during a febrile episode.\n\n\nMethods\n\nIn this prospective study, over a 1-year period, all cancer patients admitted to two of our tertiary care centers with signs and symptoms of infection were included. Patients on targeted therapies or immunomodulators, radiotherapy or post-stem cell transplant, and immediate post-surgical (<30 days postoperative) were excluded from the study.\n\nThe study was approved by the Institutional Ethics Committee of Kasturba Medical College, Mangalore (Reg No. ECR/541/Inst/KA/2014/RR-20) (DHR Reg. No. EC/NEW/INST/2020/742) on 22.07.2021 and assigned the protocol number IEC KMC MLR-07/2021/230. The committee permitted a waiver of consent to participate from the patients as patient details and data were sourced from the case files and there is no direct contact between the researcher and participant.\n\nThe patients were monitored for markers of infection with complete blood count (CBC) and C-reactive protein (CRP). Peripheral blood samples from the cases were studied using the Coulter ® DXH800 hematology analyzer (Beckman Coulter Inc., Miami, FL, USA). The CBC parameters included hemoglobin (Hb), total leukocyte count (TLC), platelet count (PLT), and differential leukocyte count (DLC). The neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were calculated using the absolute neutrophil count, absolute lymphocyte count, and platelet count. The peripheral smear stained with Leishman stain was used for morphological assessment of any evidence of infections, such as toxic changes, toxic granules, presence of immature granulocytes, presence of any virus-induced reactive lymphocytes, monocytosis, intracellular organisms, and/or hemoparasites.\n\nMicrobiological investigations were based on the clinical presentation, and an appropriate sample was collected. These investigations included microscopy, culture, serological tests, and molecular assays. Microscopy included Gram staining, Auramine-O staining, and KOH mounting. The culture was performed according to standard microbiological techniques for bacteria and fungi. Automated culture systems included the BacT/ALERT system (BioMerieux®,TM USA) for blood and sterile body fluids and MGIT (BD BACTEC®TM) for suspected mycobacterial infections. Identification of the bacteria and yeasts, and antimicrobial susceptibility testing of the isolates were performed using the VITEK 2 Compact system (BioMerieux®,TM France), and minimum inhibitory concentration (MIC) was interpreted using the Clinical and Laboratory Standards Institute (CLSI)12 guidelines. Serological and molecular tests were performed according to the clinician’s request.\n\nDemographic and clinical data were extracted from the medical records, including the type of cancer, cancer treatment, clinical presentation, laboratory investigations, radiology findings, use of antibiotic/antifungal treatment, and outcome. Episodes of Febrile Neutropenia (FN) have been documented. FN was diagnosed in the presence of a single oral temperature of ≥38.3°C (101 °F) or 38.0°C (100.4 °F) for more than 1 h along with an absolute neutrophil count (ANC) ≤500/μl or ≤1000/μl with predicted rapid decline during the next 48hr.8\n\nThe collected data were entered into MS Excel, analyzed, and presented in the form of tables, pie charts, and bar diagrams. The Mann-Whitney U test was used to assess the statistical differences between the neutropenic and non-neutropenic groups, and the chi-square test was used to analyze the distribution of categorical variables. All data were analyzed using JAMOVI software version 2.4.14. Statistical significance was set at p <0.05.\n\n\nResults\n\nThe study included 21 patients with solid or hematological malignancies, with a total of 31 febrile episodes. The mean age of the patients was 53.3 years with a male-to-female ratio of 3:1 (15 males and 6 females). There were 12 solid malignancies and 9 hematological neoplasms. Table 1 shows the various types of malignancies and distribution of cases presenting with febrile episodes.\n\nFebrile episodes in hematological malignancies were noted in older individuals compared to solid malignancies. There was a striking male predominance across all types of malignancy, presenting with febrile episodes. Table 2 shows the demographic and hematological profiles of the patients.\n\n* p <0.05, and statistically significant.\n\nThere were a total of 11 febrile neutropenic episodes, of which 6 episodes were in solid malignancies [1 episode in IDC case, 1 in metastatic seminoma, 3 in bone tumors, and 1 in esophageal SCC], and 5 were in hematological malignancies [1 in LBL, 1 in ALL, 2 episodes in AML and one in DLBCL cases]. Table 3 shows the differences in the demographics and hematological profiles of febrile neutropenic and febrile non-neutropenic patients.\n\nWBC count, percentage of neutrophils, and absolute neutrophil and platelet counts were significantly lower in febrile neutropenic patients. Additionally, the absolute lymphocyte count was reduced, with a strikingly lower NLR ratio in patients with neutropenia than in those without neutropenia. However, there were no statistical differences in the CBC parameters of febrile episodes between solid and hematological malignancies.\n\nAmong the 31 febrile episodes during the study period, 16 episodes were observed in patients with solid organ tumors and 15 febrile episodes were observed in patients with hematological malignancies. Infectious etiology was documented with microbiological evidence in 15 episodes (48.4%) and supportive radiological or laboratory evidence in nine episodes (29.0%). Seven episodes (22.6%) were unexplained and were documented as clinical sepsis.\n\nMicrobiological evidence of infections was available in 10/15 febrile episodes in hematological malignancies compared to 5/16 febrile episodes in solid malignancies, which was statistically significant. Laboratory evidence, including radiological evidence, was present in 14/15 episodes in hematological malignancies compared to 10/16 episodes in solid malignancies, with a significant p-value of 0.0218. Unexplained clinical sepsis was statistically more common in solid malignancies (6/16 episodes) than in hematological malignancies (1/15).\n\nOf the 18 bacterial infections, 15 showed documented microbiological evidence. Fungal and viral etiology was suspected in four episodes each, with microbiological confirmation of fungal etiology in two episodes (invasive aspergillosis) and viral etiology (SARS CoV-2) in one episode. Polymicrobial infections were noted in two episodes (6.5%).\n\nInfectious etiologies were identified in 71.4% of patients with febrile neutropenia for > 5 days, whereas there was no confirmed laboratory diagnosis in 75% of patients with febrile neutropenia for ≤ 4 days. On average, bacterial infections were found to develop within 2 days following the development of neutropenia, whereas viral and fungal infections usually manifested if neutropenia persisted for 5 and >7 days, respectively.\n\nUrinary tract infections accounted for 50% of the episodes, with respiratory tract infections (RTI), bloodstream infections (BSI), and skin and soft tissue infections (SSTI) in 37.5%, 20.8%, and 20.8% of the episodes, respectively. Multi-site infections were observed in four episodes (16.7%), of which three episodes were noted in patients with febrile neutropenia (p = 0.03). Urinary tract infections were the most common infections observed in patients with hematological malignancies (41.7%) and solid organ tumors (36.8%). Eighty % of BSI and 67% of RTI were observed in patients with hematological malignancies.\n\nMost infections were caused by gram-negative bacilli (72.2%), with E. coli being the most common (69.2%). Enterococcus faecalis was observed in 80% of the infections caused by gram-positive cocci. All E. coli isolates were ESBL producers, and carbapenem resistance was observed in 100% of the Acinetobacter baumannii isolates and 50% of the Klebsiella pneumoniae isolates. All E. faecalis isolates were sensitive to beta-lactams, whereas all Enterococcus faecium isolates were vancomycin-resistant.\n\nMortality rates were significantly higher in patients with neutropenia than in those without neutropenia (p = 0.0384). Sixty-seven percent of fatalities among febrile neutropenia episodes had a prolonged neutropenia duration of > 12 days. Among fatalities, 75% were observed among patients with hematological malignancies, all of whom had bacterial infections with positive cultures.\n\n\nDiscussion\n\nNeutropenia is one of the most important risk factors for infection in cancer patients. The degree and duration of neutropenia corresponds to the severity of infection. Infection rates are inversely proportional to the absolute neutrophil count, with the highest incidence of infection seen with ANC <100μl.7 Infectious etiologies are more likely to be identified in patients with longer durations of neutropenia (>7 days),5,13 with a high risk of fungal infections. In our study, we did not observe a preponderance of infections during episodes of febrile neutropenia; however, multi-site infections were significantly more likely to occur. Infectious etiologies were identified in 75% of episodes with a longer duration of neutropenia. All cases of fungal pneumonia developed after prolonged neutropenia for more than a week and were caused by Aspergillus spp.\n\nBacterial infections are the most common type of infections in patients with cancer. ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens are prominent in bacterial infections and antibiotic resistance in cancer patients.14 Gram negative bacilli accounted for 72.2% of infections, with similar rates reported in other studies.6,15 In a study conducted by Bhat et al.,6 Pseudomonas aeruginosa and Klebsiella pneumoniae were among the top gram-negative bacilli that cause infections. E. coli was the etiological agent in 50% of the infections we reported, responsible for 66.7% of UTI cases. The same study6 reported only 14.7% infections due to E. coli, but similar rates (69.9%) of UTI.\n\nFungal infections are associated with indwelling devices and are often polymicrobial in nature. Prophylactic agents against Candida spp. in patients with hematological malignancies have resulted in a surge in Aspergillus spp. infections.13 As seen in our study, pneumonia in hematological malignancies is the most common presentation of aspergillosis.\n\nThe risk of viral infections increases with T cell suppression rather than neutropenia. Immunosuppression during intensive chemotherapy predisposes patients to RTI. Reactivation of HSV, VZV, HBV, CMV, and EBV has been reported.13 Data published during the COVID-19 pandemic showed that cancer patients were more susceptible, with worse outcomes, including long COVID.16 75% of patients with viral infections presented with RTI. Although our study was performed during the pandemic, we surprisingly reported only one diagnosed case of SARS CoV-2, reflecting how the pandemic hindered patient follow-up. The patient developed a fatal secondary bacterial infection shortly thereafter. A study by Hemel et al.,16 noted that cancer patients present with few symptoms of COVID-19 as immunosuppressants administered reduce the clinical severity, suggesting an alternative theory for the low rates of COVID infections in the study. We observed a single case of clinically diagnosed HSV.\n\nA previous study at our center,6 revealed that BSI was the most common infection (33.3%) in both hematological and solid malignancies. In contrast, our data showed that 50% of all enrolled patients presented with UTI, followed by RTI (37.5%). A study by Campos et al.,17 reported a similar spectrum of infections in patients with solid malignancies. BSI is more common in Hematological malignancies,7,14,15 as seen in 80% of our patients with bacteremia. A surge in polymicrobial infections has been reported in multiple studies,5,6 however we report a low incidence of 6.7%.\n\nThe global increase in drug resistance among gram-negative organisms is alarming.6,7,13–15 All the gram-negative isolates in our study were multidrug resistant, with 69.2% ESBLs and 23.1% carbapenem-resistant organisms (CROs). A study evaluating BSIs in malignancies15 showed similar rates of resistance. They reported a higher mortality rate in drug-resistant gram-positive infections, which we did not observe in this study.\n\nUnexplained fevers in cancer pose a challenge for clinicians. Hematological biomarkers have been increasingly used as both diagnostic and predictive factors in various medical conditions, especially in oncology and infectious conditions. Morphological changes in neutrophils in the form of changes in their shape, size, and internal complexity, with functional deviations in the form of deformability and disturbances in motility, have been detected in sepsis.18 Complete blood count analysis with morphological assessment of leukocytes plays a pivotal role in diagnosing sepsis. Harada et al.,19 in his study documented a band form percentage of >10% was correlated with an increased risk of bacteremia. Left shift of granulocytes with increased number of band forms, myelocytes, and metamyelocytes can be used as a screening modality, which additionally has prognostic significance in sepsis.20 In the present study, left shift with the presence of immature granulocytes was noted more frequently in patients with solid malignancies than in those with hematological malignancies. However, the left shift was not statistically significant between the two groups or between febrile neutropenic and febrile non-neutropenic cases. In addition, we observed morphological changes in oncology patients with multiple febrile episodes. This re-emphasizes the importance of a simple ancient method of analyzing leukocyte morphology by peripheral smear examination in the early detection of sepsis. It can be a boon, especially in resource-limited centers where advanced diagnostic facilities are unavailable.21 Additionally, oncology patients receiving chemotherapy can have neutropenia, lymphopenia, and thrombocytopenia, which further compromises host immunity and hence increases the incidence of bacterial infections in such patients.22\n\nThe neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios have emerged as promising biomarkers in cancer-related particulars.23,24 In solid malignancies, NLR and PLR parameters can be utilized in correlation with tumor size-node-metastasis (TNM) staging. A lower NLR is an independent factor associated with high mortality and morbidity in sepsis.25 Similar utility of NLR in predicting febrile neutropenia in cancer patients on chemotherapy and associated increased mortality and morbidity risk has been documented.26,27 Variations of NLR values in accurately diagnosing bacteremia can be attributed to inflammatory response, marrow metastasis, infections, chemotherapy and associated hematological and lymphatic disorders.22 A study by Hwang et al.,25 in 2016 on 1395 patients, showed that initial NLR and subsequent persistent low or high values of NLR is a risk factor for predicting 28-day mortality with its increased diagnostic accuracy predicting sepsis in cancer patients. We observed a lower NLR in the patients with FN.\n\nIn the present study, PLR was higher in the febrile neutropenia group. Shen et al., in a study of 5537 patients with sepsis, documented PLR as a prognostic biomarker for increased mortality.23 Increased PLR is negatively associated with overall survival (OS) and can provide information on the therapeutic effectiveness of chemotherapy in solid malignancies.26\n\nIn conclusion, febrile neutropenia is a common complication with a high risk of morbidity and mortality among patients undergoing chemotherapy for malignancies. Multiple factors determine the patient's outcome, including the microbiological spectrum. Clinicians must understand the immune defects associated with specific cancers and their chemotherapy to anticipate infections. Appropriate antibiotics, both empirical and regimens tailored to the microbiology report, greatly reduce morbidity and mortality, especially considering the growing concern of multidrug resistance. Diagnostic modalities continue to evolve but are limited with respect to the spectrum of infections, cost, and availability. Early and rapid diagnosis remains the key to prompt intervention, for which reliable biomarkers are needed. Hematological parameters, such as TLC, platelet count, NLR, and PLR, are promising tools. These parameters were integrated with peripheral smear examination to look for morphological changes notably in neutrophils, and the presence of immature granulocytes continues to be a simple, easily available, cost-effective, and highly dependable screening tool, especially in resource-poor settings.\n\nApproval for this study was obtained from the Institutional Ethics Committee (Kasturba Medical College, Mangalore), Reg No. ECR/541/Inst/KA/2014/RR-20, DHR Reg. No. EC/NEW/INST/2020/742. The approval was given on 22.07.2021 with protocol number IEC KMC MLR-07/2021/230. The committee permitted a waiver of consent to participate from the patients as patient details and data were sourced from the case files and there is no direct contact between the researcher and participant.\n\nhttps://datadryad.org/stash/share/mDwqq0ZbZTXjIysjMD04gccBEV_Eg6TYwS5LRcsTEwI",
"appendix": "Data availability statement\n\nData excel sheet for “A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units” https://doi.org/10.5061/dryad.7sqv9s51w 28\n\nThis project contains the following underlying data:\n\n• Dryad_Data_Collection.xlsx\n\n• README_file.txt.txt (The file includes the title with the authors who have made contributions to the study, duration, location, funding and sharing and access information)\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\nKochanek M, Schalk E, von Bergwelt-Baildon M , et al.: Management of sepsis in neutropenic cancer patients: 2018 guidelines from the Infectious Diseases Working Party (AGIHO) and Intensive Care Working Party (iCHOP) of the German Society of Hematology and Medical Oncology (DGHO). Ann. Hematol. 2019 May; 98(5): 1051–1069. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKhayr W, Haddad RY, Noor SA: Infections in hematological malignancies. Dis. Mon. 2012 Apr 1; 58(4): 239–249. Publisher Full Text\n\nGirmenia C, Menichetti F: Current epidemiology and prevention of infectious complications in cancer patients. Journal-Current Epidemiology and Prevention of Infectious Complications in Cancer Patients. 2011; 07: 270. Publisher Full Text\n\nRolston KV: Infections in cancer patients with solid tumors: a review. Infect. Dis. Ther. 2017 Mar 1; 6(1): 69–83. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSafdar A, Armstrong D: Infections in patients with hematologic neoplasms and hematopoietic stem cell transplantation: neutropenia, humoral, and splenic defects. Clin. Infect. Dis. 2011 Oct 15; 53(8): 798–806. PubMed Abstract | Publisher Full Text\n\nBhat S, Muthunatarajan S, Mulki SS, et al.: Bacterial Infection among Cancer Patients: Analysis of Isolates and Antibiotic Sensitivity Pattern. Int J Microbiol. 2021; 2021(1): 1–7. Publisher Full Text\n\nMangaraj O, Barkataki D, Mohan DG: Gram negative bacilli causing blood stream infection in febrile neutropenic patients in a tertiary care centre. Int J Contemp Med Res. 2017; 4(7): 1599–1603.\n\nCarvalho AS, Lagana D, Catford J, et al.: Bloodstream infections in neutropenic patients with haematological malignancies. Infect Dis Health. 2020 Feb 1; 25(1): 22–29. Publisher Full Text\n\nLee S, Oh SY, Kim SH, et al.: Prognostic significance of neutrophil lymphocyte ratio and platelet lymphocyte ratio in advanced gastric cancer patients treated with FOLFOX chemotherapy. BMC Cancer. 2013; 13: 350. PubMed Abstract | Publisher Full Text | Free Full Text\n\nFarkas JD: The complete blood count to diagnose septic shock. J. Thorac. Dis. 2020; 12(Suppl 1): S16–S21. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSharda P, Kattupalli SC, Gajula B, et al.: Analysis of changes in blood parameter after chemotherapy in carcinoma breast: An institutional study in Northern India. Breast Journal. 2020 Dec 1; 26(12): 2431–2434. PubMed Abstract | Publisher Full Text\n\nClinical and Laboratory Standards Institute (CLSI): Performance standards for antimicrobial susceptibility testing. CLSI Informational Supplement M100. Wayne, PA: CLSI; 32nd ed.2022.\n\nDelgado A, Guddati AK: Infections in hospitalized cancer patients. World. J. Oncol. 2021 Dec; 12(6): 195–205. PubMed Abstract | Publisher Full Text | Free Full Text\n\nYusuf K, Sampath V, Umar S: Bacterial infections and cancer: exploring this association and its implications for cancer patients. Int. J. Mol. Sci. 2023 Feb 4; 24(4): 3110. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAmanati A, Sajedianfard S, Khajeh S, et al.: Bloodstream infections in adult patients with malignancy, epidemiology, microbiology, and risk factors associated with mortality and multi-drug resistance. BMC Infect. Dis. 2021 Dec; 21: 1–4. Publisher Full Text\n\nHempel L, Piehler A, Pfaffl MW, et al.: SARS-CoV-2 infections in cancer outpatients—Most infected patients are asymptomatic carriers without impact on chemotherapy. Cancer Med. 2020 Nov; 9(21): 8020–8028. PubMed Abstract | Publisher Full Text | Free Full Text\n\nTerrones-Campos C, Ledergerber B, Specht L, et al.: Risk of bacterial, viral, and fungal infections in patients with solid malignant tumors treated with curative intent radiation therapy. Adv. Radiat. Oncol. 2022 Nov 1; 7(6): 100950. PubMed Abstract | Publisher Full Text | Free Full Text\n\nZonneveld R, Molema G, Plötz FB: Analyzing Neutrophil Morphology, Mechanics, and Motility in Sepsis: Options and Challenges for Novel Bedside Technologies. Crit. Care Med. 2016 Jan; 44(1): 218–228. PubMed Abstract | Publisher Full Text\n\nHarada T, Harada Y, Morinaga K, et al.: Bandemia as an early predictive marker of bacteremia: A retrospective cohort study. Int. J. Environ. Res. Public Health. 2022 Feb 17; 19(4): 2275. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMare TA, Treacher DF, Shankar-Hari M, et al.: The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation. Crit. Care. 2015 Dec; 19: 1–1. Publisher Full Text\n\nSharma S, Pratima K, Ambedkar SN, et al.: Morphological changes in white blood cells in systemic inflammatory response syndrome (SIRS) with and without sepsis: An observational study. J. Family Med. Prim. Care. 2023 Jun 1; 12(6): 1179–1184. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMartinez JM, Santo AE, Ramada D, et al.: Diagnostic accuracy of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and neutrophil–lymphocyte-to-platelet ratio biomarkers in predicting bacteremia and sepsis in immunosuppressive patients with cancer: literature review. Porto Biomedical Journal. 2024 May 1; 9(3): 254. PubMed Abstract | Publisher Full Text\n\nShen Y, Huang X, Zhang W: Platelet-to-lymphocyte ratio as a prognostic predictor of mortality for sepsis: interaction effect with disease severity—a retrospective study. BMJ Open. 2019 Jan 1; 9(1): e022896. PubMed Abstract | Publisher Full Text | Free Full Text\n\nShi Y, Yang C, Chen L, et al.: Predictive value of neutrophil-to-lymphocyte and platelet ratio in in-hospital mortality in septic patients. Heliyon. 2022 Feb 17; 19(4): 2275.\n\nHwang SY, Shin TG, Jo IJ, et al.: Neutrophil-to-lymphocyte ratio as a prognostic marker in critically-ill septic patients. Am. J. Emerg. Med. 2017; 35: 234–239. PubMed Abstract | Publisher Full Text\n\nZahorec R: Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratisl. Lek. Listy. 2021 Jan 1; 122(7): 474–488. PubMed Abstract | Publisher Full Text\n\nHuang Z, Fu Z, Huang W, et al.: Prognostic value of neutrophil-to-lymphocyte ratio in sepsis: a meta-analysis. Am. J. Emerg. Med. 2020; 38: 641–647. PubMed Abstract | Publisher Full Text\n\nSridevi HB, et al.: A practical approach to febrile cancer patients: Diagnostic stewardship in Oncology units. [Dataset]. Dryad. Forthcoming 2024. Publisher Full Text"
}
|
[
{
"id": "322608",
"date": "23 Sep 2024",
"name": "Jayashree Kulkarni",
"expertise": [
"Reviewer Expertise Hematopathology"
],
"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, in a very simple way created awareness of the importance of accurate diagnosis of infections using basic tools like CBC and its components (ANC, ALC, NLR and PLR). These are available in a most basic laboratory and can be implemented without much difficulty.\n\nAs far as peripheral smear examination is concerned, it may be difficult and labor intensive, especially in high volume cancer care centers.\nI suggest the authors include \"other mimics of left shift should be ruled out like: 1. G-CSF (very commonly used in neutropenic patients) induced changes which also show course granulations and can be mistaken for toxic granules 2. Taxane induced Pseudo-Pelger Huet anomaly, which many may not be aware of. The language/grammar is very lucid. Adequate and appropriate references are provided. The article may be accepted for indexing with above mentioned suggestions.\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": "12587",
"date": "16 Oct 2024",
"name": "Anisha Maria Fernandes",
"role": "Author Response",
"response": "Thank you for your valuable inputs. We have addressed your comment regarding: Mimics of left shift such as G-CSF and Taxane induced Pseudo-Pelger Huet anomaly."
}
]
},
{
"id": "322615",
"date": "01 Oct 2024",
"name": "Dr Monali Gupta",
"expertise": [
"Reviewer Expertise Hematopathology",
"flow cytometry",
"cell counters",
"leukaemia",
"lymphoma",
"myeloma",
"MDS/MPNs",
"cancer genomics",
"AI"
],
"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 well written in simple and clear words. It does say that it is a prospective study but it does not mention the time period of the study undertaken as the size of the study is small. It would be good to mention in the introduction.\nIn the methods and analysis, the authors have mentioned that they have used DXH800 haematology analyser from Beckman Coulter. This analyser provides Immature granulocyte % fairly accurately. Have the authors taken the IG% from the analyser in the study or have they calculated it manually from the peripheral smears? Worth a mention in the article.\n\nReading and interpreting a peripheral smear is a skill and requires training. It is prudent to distinguish the toxic granules in the neutrophils due to infection or due to G-CSF in cancer patients. Has this been addressed?\n\nI would also recommend to include some pictures of the peripheral smears showing left shift, toxic granulations, cytoplasmic vacuolations, reactive lymphocytes, aspergillosis.\n\nAre neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios validated sepsis parameters in a clinical setting? It would be worth clarifying about these with supporting literature as many of them are still research parameters?\n\nI found this statement quite intriguing - \"In solid malignancies, NLR and PLR parameters can be utilized in correlation with tumor size node-metastasis (TNM) staging.\" Can the authors throw light on this statement and cite the reference from where it is taken?\n\nI think the article should be accepted for indexing with the above clarifications and recommendations.\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? Yes",
"responses": [
{
"c_id": "12588",
"date": "16 Oct 2024",
"name": "Anisha Maria Fernandes",
"role": "Author Response",
"response": "Thank you for your valuable inputs. We have addressed your comments regarding: Study period. Method of calculation of immature granulocyte %. Differentiation of toxic granules in the neutrophils due to infection or due to G-CSF. Peripheral smears showing toxic granulations, left shift and toxic vacuolation in neutrophils. Discussion and reference on utility of NLR and PLR as biomarkers of sepsis. Clarification and reference for utilization of NLR and PLR parameters in correlation with tumor size node-metastasis (TNM) staging in solid malignancies."
}
]
}
] | 1
|
https://f1000research.com/articles/13-997
|
https://f1000research.com/articles/11-135/v1
|
02 Feb 22
|
{
"type": "Clinical Practice Article",
"title": "The first report on detecting SARS-CoV-2 inside human fecal-oral bacteria: A case series on asymptomatic family members and a child with COVID-19",
"authors": [
"Carlo Brogna",
"Simone Cristoni",
"Mauro Petrillo",
"Domenico Rocco Bisaccia",
"Francesco Lauritano",
"Luigi Montano",
"Marina Prisco",
"Marina Piscopo",
"Simone Cristoni",
"Mauro Petrillo",
"Domenico Rocco Bisaccia",
"Francesco Lauritano",
"Luigi Montano",
"Marina Prisco",
"Marina Piscopo"
],
"abstract": "Many studies report the importance of using feces as source sample for detecting SARS-CoV-2 in patients with COVID-19 symptoms but who are negative to oropharyngeal/ nasopharyngeal tests. Here, we report the case of an asymptomatic child whose family members had negative results with the rapid antigen nasopharyngeal swab tests. The 21-month-old child presented with fever, diarrhea, bilateral conjunctivitis, and conspicuous lacrimation. In this study, analysis for the presence of SARS-CoV-2 in fecal samples by using Luminex technology allowed accurate detection of the presence of the viral RNA in the feces of the child and of all her relatives, which thus resulted to be positive but asymptomatic. It is the first time that SARS-CoV-2- is observed inside human fecal-oral bacteria and outside a matrix resembling extracellular bacterial lysates, in agreement with a bacteriophage mechanism with the images obtained by transmission electron microscopy (TEM), post-embedding immunogold, and by fluorescence microscope. In addition to the typical observations of respiratory symptoms, accurate evaluation of clinical gastrointestinal and neurological symptoms, combined with efficient highly sensitive molecular testing on feces, represent an efficient approach for detecting SARS-CoV-2, and for providing the correct therapy in challenging COVID-19 cases, like the one here reported.",
"keywords": [
"SARS-CoV-2",
"gut microbiota",
"bacteriophage",
"feces",
"diarrhea",
"nasopharyngeal swab",
"fecal oral transmission",
"TEM image",
"case series"
],
"content": "Introduction\n\nIn the past two years, humanity has been combating the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a positive, single-stranded RNA virus of the Coronaviridae family, specifically of the subfamily Orthocoronavirinae (usually called “coronaviruses”). Its closest known relatives are those found in bat feces, like the coronavirus RaTG13.1 Xu et al. (2020)2 studied viral behavior in 10 children, ranging in age from two months to 15 years. Although all of them were positive to the initial nasopharyngeal test, for eight of them, the viral charge was also positive in the stool. Moreover, they continued to test positive in the stool even after the negative nasal swab for several days after hospital discharge. In another Chinese study, the researchers found viral positivity in the fecal samples of 205 patients.4 Many studies3–5 have observed that fecal-oral transmission of the virus is possible and that it is very common to detect this virus in feces. Nevertheless, in comparison to the closest SARS-like viruses, SARS-CoV-2 appears to diverge in the receptor-binding domain of the spike glycoprotein, which is considered a key player in the entrance of the virus in human eukaryotic cells throughout its interaction with the angiotensin-converting enzyme 2 receptor (ACE-2), which in turn is considered the entry point of the virus.6 ACE-2 receptors and host cell transmembrane serine protease 2 (TMPRSS2) are abundant throughout the intestinal tract7,8 and several studies have reported altered intestinal bacterial flora or intestinal bacterial co-infection in COVID-19 patients. In terms of hosts, coronaviridae members are neither human-specific nor new in terms of discovery and treatments: a recent review describes the numerous zoonoses caused by the Coronaviridae family members,9 and scientists searched for the pathogen in the stool,10 a method that was, and continues to be, very common in the veterinary field. Among the coronaviruses previously found and analyzed in feces, there are those responsible for animal diseases like the calves’ enzootic pneumonia (caused by Bovine coronavirus, BCoV), or the porcine epidemic diarrhea (caused by the Porcine Epidemic Diarrhea Virus, PEDV). These diseases and other coronavirus-related ones very often show as initial clinical manifestation of violent diarrhea, and the affected animals have a significant alteration of the intestinal mucosa.9,11,12 Observations of possible links between the animal gut microbial environment and coronaviruses have been reported over time, supported also by the use of transmission electron microscopy (TEM) image analysis which screens and looks for viruses-like particles.8,13 The observation of SARS-CoV-2 particles by TEM can complement the molecular traces of it.14 Finally, it is worth noting that almost all of the latest characterized SARS-like viruses have been found and sequenced in bat fecal samples.15\n\nHere, we report the case of a symptomatic child whose family members had negative results with rapid antigen nasopharyngeal swab test. Analyses of fecal samples detect the viral RNA presence in the feces of the child and of all her relatives, which thus resulted to be positive asymptomatic. Microscope image analyses confirm the presence of SARS-CoV-2-like particles on fecal samples of the family and suggest that bacteria, reservoirs of the virus, are the most critical factors of fecal-oral transmission in this pandemic. The present case report also emphasizes the importance of the rapid detection of SARS-CoV-2 in symptomatic and non-symptomatic subjects with negative results from nasal and oropharyngeal swabs by analyzing stool samples, and emphasizes the importance of the bacteriophagic mechanism of the virus and its fecal-oral transmission.\n\n\nCase series description\n\nA 21-month-old female, Caucasian child, presented to us with severe bilateral conjunctivitis, conspicuous lacrimation, diarrhea, malodorous stools, restlessness, and fever (38°C). The child’s medical history was negative for any disease. Parents reported that about a year earlier, she had a period when she had a severe cold. They were alarmed by violent diarrhea, which was preceded by 24 hours of constipation, as well as by the abnormal bilateral conjunctivitis with uncontrollable lacrimation. Rapid blood tests showed the following values (in bold are those out of normal range, NR): creatinine 0.18 mg/dL (NR: 0.40-1.10 mg/dL); glucose 97 mg/dL (NR: 60-110 mg/dL); aspartate transaminase 45 I.U. (NR: 10-50 I.U.); alanine transaminase 28 I.U. (NR: 10-35 I.U.); sodium 139 mEq/L (NR: 136-150 mEq/L); potassium 5.82 mEq/L (NR: 3.50-5.10 mEq/L); chloride 95 mEq/L (NR: 98-107 mEq/L); calcium 5.50 mEq/L (NR: 4.25-5.25 mEq/L); C-reactive protein 2.60 mg/L (NR: 0-5 mg/L); iron 28 mcg/dL (NR: 59-158 mcg/dL). Other complete blood count values were in the normal range.\n\nThe Caucasian family (six adults, three children) came to us, in the autumn of 2020, during one of the Italian regional lockdown periods. Some specific information on the family members were recorded, including age, sex, medical history, occupations, and relationships (see Table 1). They live in close proximity, divided among three apartments in one building (Figure 1 panel A). The parents reported that the children never had a babysitter since this task was entrusted to their grandparents, who were in their building. Moreover, they reported that since the outbreak of the pandemic (March 2020), they had adopted a series of measures, probably excessive in their opinion, with the purpose of protecting the grandparents and children from sickness. Such measures included no contact with people outside the family context, disinfection of every product purchased, no summer holidays, no eating at restaurants or other public places, and limited outings for the four parents (am1, af1, am3, af3) for work reasons only. The grandfather (am2), grandmother (af2), and the three children (cf1, 2cf1, cm3) did not leave the building for the duration of the lockdown (Figure 1A and Table 1). All the parents (am1, af1, am3, af3) of the children working in the health care sub-area left home daily to work, and one of them worked in another geographical region. Considering their work position it is most likely that the family infection started with the contagiousness of one of the four parents (am1, af1, am3, af3) who were asymptomatic during working hours. Of interests is the medical history of one adult (am1), the father of child cf1 (our COVID-19 patient), that was hospitalized precisely one year prior (autumn 2019) with escalating symptoms of violent diarrhea, abdominal pain, fever (38°C), dyspnea, cough, headache, shortness of breath, and fainting. There was saturation of 91 SpO2%, right bundle branch block, increased D-Dimer, increased liver values (GOT and GPT), and mild lymphopenia, treated with antibiotics.\n\n(A) Distribution of the nine people analyzed in the family. Red (cf1: child female family 1) shows the child who was symptomatic and had positive results on the fecal molecular test. Yellow: the other family 1,2,3 members (Am1: adult male family 1; af1: adult female family 1; 2cf1: 2nd child female family 1; am2: grandfather family 2; af2: grandmother family 2; am3: adult male family 3; af3: adult female family 3; cm3: child male family 3) who had positive results on the Luminex molecular fecal test but negative results on the rapid antigen nasopharyngeal swab test. (B) Positive control of fecal bacteria, at 30 days, with Luminex molecular test (arbitrary unit, AU)-which confirmed the presence of SARS-CoV-2 (520 AU) after 30 days of bacterial culture. (C-D) Viral load (Luminex bead count- AU) initially and after 60 days. The family members hired supplemental therapy with colloidal copper and bromelain, as well as with probiotics therapy with Lactobacillus reuteri and Bacillus clausii.\n\nWe initially performed rapid antigen nasopharyngeal swab test (COVID-19 Ag Rapid Test Device, Abbott 41FK10) on the child (cf1), and it was negative. The same test was also performed on the parents (am1, af1) and the other six family members, and all results were negative. We had, in line with previous studies,16,17 experience of multiple negative results SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction (RT-PCR) tests on oropharyngeal/nasopharyngeal (OP/NP) swab samples from individuals with a strong clinical suspicion of COVID-19.18 Being in the presence of a very young patient, it was decided to adopt a fast high-throughput COVID-19 screening approach to detect the presence of SARS-CoV-2 directly from stool samples: in the following 24 hours, stool samples were collected from all nine family members, and molecular testing for SARS-CoV-2 was performed by using Luminex technology19,20 as described by us previously.21 Negative and positive controls as bacterial cell cultures of stool samples were those used and described in this previous study.21\n\nA summary of the analyses is reported in Figure 1C-D and Table 1: all family members had positive results to the Luminex molecular test, and the child with symptoms (cf1) showed the highest value of the Luminex assay. The other family members did not manifest any symptoms, despite being positive for the presence of viral RNA in their stools.\n\nThe child was treated for 48 hours only with rehydration and probiotics only; because of the absence of significant symptoms such as cough or dyspnea, no cortisone or antibiotics were administered. Conjunctivitis and lacrimation ceased about 72 hours later and the patient was discharged. The entire family, including the reported patient, were then instructed to take probiotics (Lactobacillus reuteri, 100 million units, one time per day, and Bacillus clausii 2 billion units, per day) in addition to bromelain, 300 mgr. per day, and colloidal copper, 20 ppm (parts per million) per day for 30 days. After 60 days, both the rapid antigen nasopharyngeal swab test (COVID-19 Ag Rapid Test Device, Abbot 41FK10) and the Luminex test were repeated: all family members were negative to the rapid antigen tests, and only one family member (Figure 1D -am1) continued to have Luminex positive results. Patient am1, male, Caucasian and a healthcare employee, continued the treatment until he became negative at day 90 for the presence of SARS-CoV-2 in stools. Bacterial feces of this patient, after 30 days of bacterial culture, have been analyzed by TEM, immune-EM, and by fluorescence microscopy, and a set of obtained images is shown in Figure 2. At day 30 of bacterial culture of feces patient am1, the Luminex molecular test confirmed the presence of SARS-CoV-2 and the RNA viral load count was increased from 24 arbitrary unit (AU) (initial) to 520 AU (Final) (Figure 1B) in accordance with our previous observations.21 Transmission electron microscope images (panels A and B of Figure 2-Tecnai G2 Spirit BioTwin; FEI, equipped with a VELETTA CCD digital camera -Soft Imaging Systems GmbH) SARS-CoV-2 (black arrows) inside a bacterium (A) and outside a matrix resembling extracellular lysate of a bacterium (B). No eukaryotic cells have been ever observed after 30 days of bacterial culture. Post-embedding immunogold (Figure 2 Panel C, D): bacteria pellets were fixed with a mixture of 0.05% glutaraldehyde of 4% paraformaldehyde in 0.1M PBS (Phosphate-buffered saline) buffer, washed in PBS buffer, pelleted at 10000g and included in 3% agarose. The agarose block was cut into tissue-size pieces and the slices were post-fixed in 2% OsO4, dehydrated in a series of ethanol solutions of increasing concentration and in propylene oxide and finally embedded in Epon 812. Thin sections were cut from embedded specimens using Reichert Jung Ultra microtome and are applied to Formvar/Carbon Supported nickel grids. Sections were blocked with normal goat serum for 1h at room temperature, incubated with rabbit monoclonal to SARS-CoV-2 nucleocapsid protein antibody (EPR24334-118, Abcam) and then with secondary anti-rabbit antibody 10nm gold-conjugated (Aurion). Electron microscopy images were acquired from thin sections under an electron microscope (Tecnai G2 Spirit BioTwin; FEI) equipped with a VELETTA CCD digital camera (Soft Imaging Systems GmbH).\n\nImages were obtained at day 30 of bacterial culture of patient am1’s feces, in which a molecular test with Luminex confirmed the presence of SARS-CoV-2 and an increase of RNA viral load from initial 24 arbitrary unit (AU) to 520 AU final. (A-B) Transmission electron microscope images (panels A and B -TEM FEI- Thermo Fisher Tecnai G2 operating at 120 kV) show SARS-CoV-2 (indicated by black arrows) inside a bacterium (A) and outside a matrix resembling extracellular lysate of a bacterium (B). (C-D) Post-embedding immunogold: rabbit monoclonal to SARS-CoV-2 Nucleocapsid protein antibodies ligating to the secondary anti-rabbit antibody 10nm gold-conjugated indicated the virus inside bacteria of gut microbioma (Tecnai G2 Spirit BioTwin; FEI equipped with a VELETTA CCD digital camera (Soft Imaging Systems GmbH)).\n\nThe immunofluorescence microscope (Figure 3, panels A; B, C, D - Zeiss Axioplan 2, Axiocam 305 color, magnification 100×) was performed in according to manufactures’ protocol,22,23 using as primary antibodies versus SARS-CoV-2 Nucleocapsid protein (“Sars Nucleocapsid Protein Antibody [Rabbit Polyclonal] - 500 μg 200-401-A50 Rockland”, and the “Goat anti-Rabbit IgG (H+L) Cross-Adsorbed Secondary Antibody, Cyanine3 #A10520” as secondary antibody). It was used also a primary antibody versus gram-positive bacteria (“Gram-Positive Bacteria Ab (BDI380), GTX42630 Gene Tex”) and “Goat anti-Mouse IgG (H+L), Super-clonal™ Recombinant Secondary Antibody, Alexa Fluor 488” as secondary antibody. The images confirm the presence of SARS-CoV-2 particles (red light in the fluorescence images) in relationship with the bacteria (green light in the fluorescence images).\n\nPanels A, B, C, D (Zeiss Axioplan 2, Axiocam 305 color, magnification 100×) show immunofluorescence staining versus SARS-CoV-2 nucleocapsid protein (red light), gram positive bacteria (green light). Panel E is the negative control. The roman numerals I,II,III,IV and yellow rectangles indicate four gram-positive bacteria (green light) infected by SARS-CoV-2 (red light).\n\nTo our knowledge, this is the first time that a member of coronaviruses’ family, the SARS-CoV-2, has been observed inside human fecal-oral bacteria (Figure 2 panel A – Figure 2 panel C) and outside a matrix resembling extracellular bacterial lysates (Figure 2, panel B), in agreement with a phage-like behavior reported by us.21\n\n\nDiscussion\n\nZheng F. et al.24,25 observed that gastrointestinal symptoms are common in children with SARS-CoV-2 and are associated with fever, nausea, vomiting, and abdominal pain. However, their case series is probably not very large both because it is known that more than half of sick children have mild to moderate symptoms and because hospitalizations are not as common as for other respiratory viruses.24 A recent example of the fecal-oral transmission is well described in a short communication by Hansen et al.26 These authors reported the case of an 86-year-old man who, despite of having been vaccinated (first dose of BNT162b2 mRNA COVID-19 vaccine), eighteen days after vaccination was admitted to the hospital for diarrhea, with no other symptoms of COVID-19, and had negative results on antigen and PCR testing until day 26, when he died of acute renal and respiratory failure. On day 24, the older man's roommate tested positive for SARS-CoV-2 RT-PCR on a nasal swab. Autopsy results of the 86-year-old decedent indicated the presence of the virus in the organs examined except for the liver and olfactory bulb.\n\nIn one of the first studies on SARS-CoV-2 in Wuhan, prominent symptoms of COVID-19 patients are described, including diarrhea27 and in children, gastrointestinal disorders are the most prevalent.24 The persistence of coronaviruses in feces, for a long time, had already been observed many years ago. In one of the first case reports of 1982, Baker et al.28 described the case of a 47-year-old Indian man who underwent surgery for a duodenal ulcer when he was 13 years old. The symptoms that forced hospitalization were diarrhea and steatorrhea. The man was monitored for eight months, and in 17 fecal samples, coronavirus-like particles were observed by electron microscopy. The images show two ovoid/geoid shaped coronavirus particles with the spike protein evident and one circular shaped coronavirus particle but without surface proteins, like those here reported in Figure 2.\n\nInclusion of symptoms other than respiratory, such as gastrointestinal symptoms, seems to be very important in the diagnostic process. Although diarrhea and conjunctivitis with lacrimation, as in our case, may be unlinked, they can be related to each other if the gut microbiota and the central, peripheral, and autonomous nervous systems are taken into account. The gut microbiota29 seems to be extremely important and interconnected with the central, peripheral, autonomic, neuroimmune, and neuroendocrine nervous system axis. An altered gut microbiota or the total absence of bacteria, as in germ-free mice, can affect areas of the brain, including the hippocampus, the point of end of olfactory system.30 Several studies have reported an impairment of intestinal gut microbiota31 or respiratory and intestinal bacterial coinfection in COVID-19.32\n\nAs shown in Figures 2-3, bacteria could play crucial role in the possibility of fecal-oral transmission. This news isn’t so far away from the most recent studies21 in which we described that RNA replication of the SARS-CoV-2 virus can take place in bacterial cultures. We also described that the use of certain drugs can decrease its replication in vitro. Moreover, in the same work, we observed, by mass spectrometry, the mutational phenomenon of viral proteins in bacterial cultures. Other authors have also noted the possibility that the spike protein of the SARS-CoV-2 may interact with the lipopolysaccharide of Escherichia coli33 or that the absence of proteobacteria could play a key role in the pathogenesis of respiratory viral diseases.30 This is why early localization in the stool assumes considerable importance. Since the discovery of SARS-CoV-2, a plethora of commercial tests have become available, and, currently, more than 1,700 tests are commercialized in the European Union countries (source JRC COVID-19 In Vitro Diagnostic Devices and Test Methods Database34). Rapid Antigen Tests (RATs) are recommended to be routinely used,35,36 especially on oropharyngeal/nasopharyngeal (OP/NP) swab samples. Researchers have had sometimes problems in terms of sensitivity and specificity with some of them.37 Problems may arise because the tests were initially evaluated on samples from patients with severe COVID-19, who are suggested to develop a much higher immune response than those with mild or asymptomatic disease.38\n\nRT-PCR is considered the gold standard method for detection of SARS-CoV-2. However, we had previous experience of multiple negative results SARS-CoV-2 RT-PCR tests on OP/NP swab samples from individuals with a strong clinical suspicion of COVID-19.18 Mardian et al. 2021 recommend fecal detection of viral RNA when nasopharyngeal swab data are questionable.39 In addition, the RNA virus could be present in the 48,1% of patients who were negative to OP/NP swab tests until 33 days.20 Finally, in a recent study aimed to evaluate the role of fecal-oral transmission, unique RNA SARS-CoV-2 genomic sequence mutations have been observed by performing next-generation sequencing on the fecal samples.17 In this case the Luminex technology as molecular testing tool was chosen because it is ideal for fast high-throughput COVID-19 screening and its clinical performance have been evaluated.40\n\nIn consideration that SARS-CoV-2 was detected at low levels in fecal samples,41 in addition to molecular test, was agreed to verify the presence of the virus by acquiring images of at least one sample. As proposed by Dittmayer and colleagues,14 in the case of COVID-19 diagnosis, the use of image analysis to confirm the presence of SARS-CoV-2 particles complements detection of molecular traces of SARS-CoV-2 specific proteins or nucleic acids (and vice versa). In studies of infectious diseases, TEM is used very often to definitively prove the presence of an infectious unit. The images were obtained by TEM, immune-EM, and by fluorescence microscope. What we have noted is (in agreement with our first observations21), there is a crucial role of bacteria in the fecal-oral transmission of SARS-CoV-2. The only limitations of such investigations are the high costs and long waiting times.\n\n\nConclusions\n\nHere, we report the case of a symptomatic child for COVID 19, brought to her by one of the parents, whose family members had negative results with rapid antigen nasopharyngeal swab test. Analyses of fecal samples by high-throughput COVID-19 screening (Luminex technology) allowed us to accurately detect the viral RNA presence in the faces of the child and of all her relatives, which thus resulted to be positive asymptomatic.\n\nMicroscopy images analysis was used as complementary approach to confirm the presence of SARS-CoV-2 in bacterial cultures obtained by fecal sample of an infected individual with the viral RNA load positive individual. The images obtained by TEM, immune-EM and by fluorescence microscope show SARS-CoV-2 inside human gut bacteria and outside a matrix resembling extracellular bacterial lysates, in agreement with a bacteriophage mechanism.21 This surprising finding allows us to better clarify the first fecal-oral transmission of the virus and clearly shows that the reservoir of the virus is neither adults nor children but simply bacteria.\n\nWe believe that accurate analysis of the human gut microbiome during viral infections, including SARS-CoV-2 infections, may be of great importance and may aid in diagnosis when other tests fail.18 According to the other studies39 faster and more versatile tests should be improved to decrease or cope with the contagiousness of the pathogens, especially to detect them in the stools. The observation of all clinical symptoms, typically respiratory, gastrointestinal, and neurological, combined with molecular testing (stool, sputum, tear, other fluids) and image analysis, represents the key for understanding the interaction of SARS-CoV-2 with the human microbiome. Therefore, for the provision of the correct epidemiology, diagnosis and accurate therapeutic approach is important in the treatment of COVID-19, especially in challenging cases, such as the one reported here. This case also highlights the possibility of contagion from asymptomatic parents to their children.\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 their clinical details and clinical images was obtained from the parents of the child. Written informed consent for publication of their clinical details and clinical images was also obtained from all other patients involved in the study.",
"appendix": "Acknowledgments\n\nWe thank Tigem Institute-Telethon Pozzuoli Naples for the microscope electron images preparations. We thank Biogem Institute of Ariano Irpino (Av), for fluorescence microscope images preparations. We also are grateful to Electron microscopy facility of the department of chemical sciences- University of Study Federico II Naples (UniNa). We are also grateful to Marsan consulting and Dr Marino Giuliano for their full support. We thank the entire family and all the patients for allowing this work. This paper is a new gift for all the children of the world.\n\n\nReferences\n\nZhang L, Shen FM, Chen F, et al.: Origin and Evolution of the 2019 Novel Coronavirus. Clin. Infect. Dis. 2020 Jul 28; 71(15): 882–883. PubMed Abstract | Publisher Full Text | Free Full Text\n\nXu Y, Li X, Zhu B, et al.: Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nat. Med. 2020; 26(4): 502–505. 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{
"id": "125777",
"date": "07 Mar 2022",
"name": "Debojyoti Dhar",
"expertise": [
"Reviewer Expertise gut microbiome"
],
"suggestion": "Approved With Reservations",
"report": "Approved With Reservations\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nReviewer comments –\nThe Figure 1B legend needs to be properly written or displayed.\n\nFigure 1C, correct the spelling of culture as in Bacteria culture (legend).\n\nIn Table 1, data pertaining to the nasopharyngeal swab test need to be presented for all the subjects.\n\n“At day 30 of bacterial culture of feces patient am1, the Luminex molecular test confirmed the presence of SARS-CoV-2 and the RNA viral load count was increased from 24 arbitrary unit (AU) (initial) to 520 AU (Final) (Figure 1B)...” – The figure description needs to be better (Figure 1B). The authors should better describe whose fecal sample was used in the culture in the figure description for 1B.\n\n“Bacterial feces of this patient, after 30 days of bacterial culture, have been analyzed by TEM, immune-EM, and by fluorescence microscopy, and a set of obtained images is shown...” – Instead of bacterial feces, change to feces of this patient was cultured in bacterial culture media.\n\nFigure 2D is not clear to this reviewer.\n\n“In addition, the RNA virus could be present in the 48,1% of patients who were negative to OP/NP swab tests until 33 days.” – Please correct the % depiction.\n\n“Here, we report the case of a symptomatic child for COVID 19, brought to her by one of the parents, whose family members had negative results with rapid antigen nasopharyngeal swab test.” – Please correct the grammatical error.\n\nThis reviewer has reservation on the “fecal-oral” transmission route being used by the authors. This paper and the earlier paper on this topic by the authors showed possible replication of the SARS-Cov2 virus like particles in bacterial culture. But neither observations prove the route of the viruses coming into the feces. As far as this reviewer is concerned, we still do not know how the virus gets to the gastrointestinal tract. So, instead of “fecal-oral” bacteria, gastrointestinal bacteria may be written.\n\n“This surprising finding allows us to better clarify the first fecal-oral transmission of the virus and clearly shows that the reservoir of the virus is neither adults nor children but simply bacteria.” – This reviewer does not agree with this statement especially the second half of it.\n\nOverall, this is an interesting finding and corroborates the earlier report of the same author (F1000Res. 2021 May 11; 10:370) about the presence of the SARS-Cov2 like virus particles in bacterial culture. This report is an advancement as some evidence of the presence of the virus like particles have been shown using TEM, immune-fluorescence microscopy. The presence of SARS-Cov2 in feces has been documented before and as such this report does not add anything new to this however what is interesting is the replication potential of the virus in bacterial culture. The authors might want to provide more assays and evidence to showcase the “phage-like” activity of the SARS-Cov2 as they propose.\nFinally, please crosscheck the text. Lots of grammatical and contextual errors are found, some of which have been highlighted above.\n\nIs the background of the cases’ 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 conclusion balanced and justified on the basis of the findings? Partly",
"responses": [
{
"c_id": "7941",
"date": "10 Mar 2022",
"name": "Carlo Brogna",
"role": "Author Response",
"response": "Dear Dr. Debojyoti Dhar, Thanks a lot for your valuable comments and suggestions that you have provided in the report. We will address all of them, together with those of other reviewers, in order to provide a fully revised version of the manuscript. Best regards, Carlo Brogna, on behalf of the authors."
},
{
"c_id": "8529",
"date": "21 Jul 2022",
"name": "Carlo Brogna",
"role": "Author Response",
"response": "Reviewer comments and Brogna et al. responses (R.) First of all, we apologize to the reviewer for responding only now, but we also waited for the opinion of a second reviewer who arrived in early July so that we could review the manuscript only once. The Figure 1B legend needs to be properly written or displayed. R: the legend has been replaced in the following form: “This is the positive control of patient am1's bacteria derived from a stool sample, after 30 days of bacterial culture using our previously published method (21), performed with the Luminex molecular assay. The molecular assay reported a viral RNA concentration growth of up to 520 AU (arbitrary unit).” Line 94-99 Figure 1C, correct the spelling of culture as in Bacteria culture (legend). R: Done. Line 97 In Table 1, data pertaining to the nasopharyngeal swab test need to be presented for all the subjects. R: We have added again the corrected table 1, in which there is the column with the data request. “At day 30 of bacterial culture of feces patient am1, the Luminex molecular test confirmed the presence of SARS-CoV-2 and the RNA viral load count was increased from 24 arbitrary unit (AU) (initial) to 520 AU (Final) (Figure 1B)...” – The figure description needs to be better (Figure 1B). The authors should better describe whose fecal sample was used in the culture in the figure description for 1B. Done. Line 94-99 “Bacterial feces of this patient, after 30 days of bacterial culture, have been analyzed by TEM, immune-EM, and by fluorescence microscopy, and a set of obtained images is shown...” – Instead of bacterial feces, change to feces of this patient was cultured in bacterial culture media. R: We have changed as suggested in: “The feces of this patient was cultured in bacterial culture and after 30 days, the pellet of bacteria…..” Line 133-137 Figure 2D is not clear to this reviewer. R: We apologize with the reviewer and have clarified our mistake in the legend, describing figure 2D: “(D) negative control of bacterial stool culture of a healthy person after 30 days, without primary antibody with only the secondary antibody.” Line 174-176 “In addition, the RNA virus could be present in the 48,1% of patients who were negative to OP/NP swab tests until 33 days.” – Please correct the % depiction. R: We apologize to the reviewer and thank him for pointing this out to us. There was an error in bibliography #48, which we have replaced correctly, and where the proposed data are now visible. For clarity, we rephrase the sentence in the text as follows: \"In a Systematic Review and Meta-analysis, at the beginning of the pandemic, it was observed that viral RNA was present in the stool in 48,1% of patients during the disease and that 70,3 % of patients had prolonged shedding that could extend beyond 33 days from the onset of the disease.\" (2 here, 48in the manuscript). Line 264-267 8, “Here, we report the case of a symptomatic child for COVID 19, brought to her by one of the parents, whose family members had negative results with rapid antigen nasopharyngeal swab test.” – Please correct the grammatical error. R: We replaced it with: “Here we report the case of a child symptomatic for COVID 19, transmitted by one of the parents, whose relatives had tested negative on the rapid antigenic nasopharyngeal swab test.” Line 2826-287 This reviewer has reservation on the “fecal-oral” transmission route being used by the authors. This paper and the earlier paper on this topic by the authors showed possible replication of the SARS-Cov2 virus like particles in bacterial culture. But neither observations prove the route of the viruses coming into the feces. As far as this reviewer is concerned, we still do not know how the virus gets to the gastrointestinal tract. So, instead of “fecal-oral” bacteria, gastrointestinal bacteria may be written. R: We appreciate the reviewer's critical viewpoint. In our recent paper published in ref. 3, we supported this possible additional transmission pathway. Still, the reviewer's suggestion is very cautious, and in agreement with him, we have chosen to replace the term fecal-oral bacteria with” bacteria of the human gut microbiome”. We hope he agrees. “This surprising finding allows us to better clarify the first fecal-oral transmission of the virus and clearly shows that the reservoir of the virus is neither adults nor children but simply bacteria.” – This reviewer does not agree with this statement especially the secondhalf of it. R: With all due respect to the reviewer and his valuable help in improving this article, let us argue our opinion in a few lines. If we consider how many sites report the presence of viral RNA in wastewater (4-6), as described in the current literature, although everyone knows that RNA by definition is an easily degradable (7) molecule, and if we consider how the first six miners in the Yunnah caves in China, in close contact with bat guano (feces), became ill with CORONAVIRUS RATG13 pneumonia (8-9), and furthermore if we also consider our recent work Brogna et al. (3). where we performed many other tests, we can more confidently assert that bacteria could represent a potential reservoir of the virus and, as in the work cited above, we argued that it could behave as both a lytic and lysogenic bacteriophage. However, with the caution suggested by the reviewer, we have changed the last sentence to: “This first observation invites us to pay more attention to the fecal-oral transmission route of the virus and suggests as a further possible reservoir of the virus also the bacteria of the human gut microbiome.” Line 298-300 Overall, this is an interesting finding and corroborates the earlier report of the same author (F1000Res. 2021 May 11; 10:370) about the presence of the SARS-Cov2 like virus particles in bacterial culture. This report is an advancement as some evidence of the presence of the virus like particles have been shown using TEM, immune-fluorescence microscopy. The presence of SARS-Cov2 in feces has been documented before and as such this report does not add anything new to this however what is interesting is the replication potential of the virus in bacterial culture. The authors might want to provide more assays and evidence to showcase the “phage-like” activity of the SARS-Cov2 as they propose. R: We can now reassure the reviewer on this point because the much-required evidence has been made public in the publications of Brogna et al. and Petrillo et al. (3,10), and we added some of the other results in the supplementary materials in which we have added evidence of nitrogen isotopic labeling also in viral particle proteins.. The reviewer's comments and corrections were invaluable in improving this work. We thank them for making the work solid. Finally, please crosscheck the text. Lots of grammatical and contextual errors are found, some of which have been highlighted above. The work was reviewed by a native speaker."
}
]
},
{
"id": "138763",
"date": "01 Jul 2022",
"name": "Aravind Natarajan",
"expertise": [
"Reviewer Expertise Fecal shedding of SARS-CoV-2 RNA"
],
"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\nBrogna C et al. The first report on detecting SARS-CoV-2 inside human fecal-oral bacteria: A case series on asymptomatic family members and a child with COVID-19\nThis manuscript by Brogna C et al. reports the first observation of SARS-CoV-2 “inside human fecal-oral bacteria” suggesting that SARS-CoV-2 can infect bacteria like a bacteriophage. This study is inspired by a symptomatic 21-month-old child whose nasopharyngeal sample tested negative on a rapid antigen test, but feces tested positive for SARS-CoV-2 viral RNA on a Luminex assay. This led the authors to carry out a contact tracing study, testing stool samples from family members that lived in the same building as the child for SARS-CoV-2 RNA; they found all the family members to be asymptomatic and positive for viral RNA in their stool. Notably, the child’s male parent (am1) continued to have extended shedding of viral RNA out to 90 days from the start of treatment. The authors collected stool samples from this parent to understand the pathobiology of SARS-CoV-2.\nSpecifically, they expand on their previous observation (featuring two shared authors with the current manuscript) that this virus could potentially display bacteriophage-like behavior and infect bacteria. In this previous work, they carried out in vitro culturing assays and reported that the concentration of viral RNA increased with time when incubated with fecal bacteria1. In another publication (featuring seven shared authors with the current manuscript), the authors use TEM and immunofluorescence microscopy and report visualizing SARS-CoV-2 particles in gut bacteria2. In the current work, they feature these same in vitro and microscopy experiments with a different stool sample and report the same conclusion - that bacteria in the gut are infected with SARS-CoV-2 viral particles.\nI recommend this manuscript be rejected in its current form. It may be sent out for reviews again pending major revisions.\n\nMajor suggestions:\nThroughout the manuscript, the authors suggest the fecal-oral transmission of SARS-CoV-2. However, whether there are infectious viral particles in stool capable of being transmitted is at best still debated, with more evidence to the contrary3. Especially given the relevance of this matter to clinical decisions and public health, I encourage the authors to present a balanced view.\n\nThe authors report viral RNA concentration determined through Luminex in arbitrary units (AU). However, my understanding is that Luminex can be set up to contain standards that reveal an absolute concentration of viral RNA. Given how viral RNA concentrations are central data to the conclusions in this work, I believe that reporting the absolute concentration of viral RNA is important. Additionally, this will make the observations here more replicable across labs and viral RNA detection techniques.\n\nRegarding the reported viral RNA concentrations, it is unclear what the specificity, sensitivity, and detection range of the Luminex assay are as carried out by the authors. Therefore, I recommend the authors include relevant controls to estimate these. Reporting this information along with their experiments will add important validity and context to the data.\n\nFig 3 is missing key controls. Recommend including a control of uninfected bacteria from a healthy donor stained with both α-SARS-CoV-2 nucleocapsid protein antibody and α-Gram-positive bacteria antibody.\n\nThe authors conclude from the microscopy data that fecal bacteria are infected by SARS-CoV-2 in samples collected on day 30 from an adult patient, am1. Notably, this patient along with the others in the study was prescribed probiotics with two Gram-positive bacteria (Lactobacillus reuteri and Bacillus clausii) in their diets for 30 days prior to sample collection. In the event that bacteria are in fact infected by SARS-CoV-2, it is unclear if this is an artefact of the probiotic supplements and treatment regime.\n\nI encourage the authors to provide more methodological information in the manuscript. As a matter of principle, manuscripts should in and of themselves provide sufficient information for readers to repeat experiments without having to go down the rabbit hole of chasing down references to other works. The current manuscript exhibits this concern that is prevalent in scientific publications. Some instances of this in the current manuscript include -\n\n“molecular testing for SARS-CoV-2 was performed by using Luminex technology as described by us previously” - It is unclear how the samples were prepared, if controls were included and what the parameters of this assay were. Methodology used to isolate and culture bacteria from stool - It is unclear how bacteria were isolated from stool. This is important information to get a sense of how rigorous this method was, whether there are inherent biases regarding what bacteria are favored in the culturing process and if there are chances for other residual contaminants from the fecal sample. Methodology used to collect and preserve stool samples - the majority of existing reports are unable to culture viable SARS-CoV-2 from fecal samples, even when the samples are preserved in Viral Transport Media (VTM). Therefore, clarity about how the current work collected and preserved samples are crucial to understanding how they have been successful at recovering viable viral particles.\n\nMinor suggestions:\nRequest citation and clarity on the statement - “several studies have reported….intestinal bacterial co-infection in COVID-19 patients”.\n\nRequest citation and clarity on the statement - “Observations of possible links between the animal gut microbial environment and coronaviruses have been reported over time”. The current citations do not have evidence for a possible link to the gut microbial environment.\n\nFig 1 reports “Viral load” although what is actually reported is the viral RNA concentration, which can be different from viral load because not all viral particles are lysed and provide RNA for detection, and some viral RNA is reported to come from non-viral reservoirs4.\n\nThe manuscript calls for major editorial revisions given numerous improper usages of phrases. For instance - a) There are no “fecal-oral bacteria”, which suggests specific bacteria in the feces are able to be transmitted orally. b) It is unclear what “Bacterial feces” means. c) “RNA viral load count” appears miswritten.\n\nAdditional notes:\nI don’t have experience with interpreting TEM images and therefore leave this comment here rather than as a cause for major revision. TEM images are complex requiring the appropriate collection and processing of samples, the inclusion of controls, and careful interpretation of observations. The improper use of EM to study SARS-CoV-2 from tissue samples has been a cause for concern5,6. To my untrained eye, Fig 2 seems to be another example of misinterpreted EM data because -\n\nIf Fig 2a in fact displays SARS-CoV-2 viral particles inside a bacterium, it is surprising to me that the bacterial host appears to be entirely filled by viral particles with no room for its essential, native molecules. To me, this figure seems like that of the widely described multivesicular bodies that are unrelated to SARS-CoV-2 and yet regularly misinterpreted6.\n\nThe figures don’t appear to have sufficient resolution to highlight the ultrastructures typical of SARS-CoV-2 that are required to unmistakable identify viral particles5. If Fig 2b in fact presents the case of a bacteria with viral particles around it, it merely appears like viral particles proximal to the bacteria in this image, with no evidence that these viruses in fact infected the bacteria. The conclusion that viral particles are found in the extracellular matrix of gut bacteria is an over-reach without sufficient evidence. The figure is missing controls such as stained and unstained images of comparable bacteria without the presence of the alleged SARS-CoV-2 viral particles. Given these observations and the importance of this figure to the central tenet of this manuscript, I recommend the editorial team seeks input from an expert in TEM.\n\nThe hypothesis that SARS-CoV-2 may infect bacteria is both biologically fascinating and clinically highly relevant. This is because there are no examples that I know of or can find of viruses that affect humans that can also retain the molecular machinery to affect bacterial cells. Therefore, the idea that this is possible is biologically fascinating and can pave the path to many follow-up studies. Further, SARS-CoV-2 continues to be a major threat, having claimed over 6 million people worldwide. Therefore, careful evaluation of the potential sources of future outbreaks is critical from a personal and public health standpoint. If in fact bacteria in the gut can harbor infectious SARS-CoV-2 viruses, this adds to another dimension of the COVID-19 pandemic that calls for urgent precautionary measures. Unfortunately, the current manuscript is missing many controls and methodological details, and has insufficient data to make the case that bacteria are in fact infected by SARS-CoV-2. Given the hugely significant impact that concluding gut bacteria can be infected by SARS-CoV-2 through a bacteriophage-like property can have to humanity, I encourage the authors and editorial team to exercise caution and responsibility in promoting this conclusion with insufficient evidence.\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? 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 conclusion balanced and justified on the basis of the findings? No",
"responses": [
{
"c_id": "8528",
"date": "21 Jul 2022",
"name": "Carlo Brogna",
"role": "Author Response",
"response": "Reviewer comments and Brogna et al. responses (R.) Brogna C et al. The first report on detecting SARS-CoV-2 inside human fecal-oral bacteria: A case series on asymptomatic family members and a child with COVID-19 This manuscript by Brogna C et al. reports the first observation of SARS-CoV-2 “inside human fecal-oral bacteria” suggesting that SARS-CoV-2 can infect bacteria like a bacteriophage. This study is inspired by a symptomatic 21-month-old child whose nasopharyngeal sample tested negative on a rapid antigen test, but feces tested positive for SARS-CoV-2 viral RNA on a Luminex assay. This led the authors to carry out a contact tracing study, testing stool samples from family members that lived in the same building as the child for SARS-CoV-2 RNA; they found all the family members to be asymptomatic and positive for viral RNA in their stool. Notably, the child’s male parent (am1) continued to have extended shedding of viral RNA out to 90 days from the start of treatment. The authors collected stool samples from this parent to understand the pathobiology of SARS-CoV-2. Specifically, they expand on their previous observation (featuring two shared authors with the current manuscript) that this virus could potentially display bacteriophage-like behavior and infect bacteria. In this previous work, they carried out in vitro culturing assays and reported that the concentration of viral RNA increased with time when incubated with fecal bacteria1. In another publication (featuring seven shared authors with the current manuscript), the authors use TEM and immunofluorescence microscopy and report visualizing SARS-CoV-2 particles in gut bacteria2. In the current work, they feature these same in vitro and microscopy experiments with a different stool sample and report the same conclusion - that bacteria in the gut are infected with SARS-CoV-2 viral particles. I recommend this manuscript be rejected in its current form. It may be sent out for reviews again pending major revisions. Major suggestions: Throughout the manuscript, the authors suggest the fecal-oral transmission of SARS-CoV-2. However, whether there are infectious viral particles in stool capable of being transmitted is at best still debated, with more evidence to the contrary3. Especially given the relevance of this matter to clinical decisions and public health, I encourage the authors to present a balanced view. R: First, we are honored by the reviewer's comments on the fecal-oral route of transmission od the virus SARS-CoV-2 because they were our doubts at the beginning of the pandemic and were the reason we wanted to do the check on prokaryotic cells. In fact, we found it really embarrassing that no major research group in the world has documented a positive or also negative control on the interaction between Coronavirus, in general in the last 30 years, and SARS-CoV-2 in the last 2 years and prokaryotic unicellular cells. Only the famous diatribes on the occurrence of bacterial cofactor in HIV (RNA virus) infection can be found in the literature. We respect the reviewer's opinion on the epidemiology and transmission route of the virus, but we believe that in a balanced context, the oro-fecal route of transmission should also, and not only be considered. Reference 3 that the reviewer cites is a letter, a commentary by Pedersen et al. to the work of Guo et al. (7), a manuscript that collected a review of other works emphasizing the fecal-oral transmission pathway. Guo et al. (8) responded to the letter from Pedersen et al., including more recent work and reiterating that the oro-fecal route of transmission must be considered. In addition, it should be considered that historically the coronaviruses family, which afflict animals in general, have long been listed in the literature as viruses with an oro-fecal route of transmission (many studies are present in the literature). Our third paper (2) supported the addition of the oro-fecal transmission route, including many new studies in this regard after the publication of the commentary by Pedersen et al. Since the beginning of the pandemic, several authors have pointed out that SARS-CoV-2 has a close relative: the coronavirus RATG13 (9). RATG13 was discovered in 2013, and picked up by researchers following the deaths of 3 out of 6 miners working in caves in Mojiang county in Yunnan, China (10), as currently recognized. The miners worked in caves where bat guano (stool) was present, and it is really hard to imagine that in contact with such material, the transmission route was respiratory. However, the reviewer pays attention to this issue, and in line with his opinion, we have modified the text by adding the word \"also\" or \"possible\" next to \"transmission route\" where this was possible. The authors report viral RNA concentration determined through Luminex in arbitrary units (AU). However, my understanding is that Luminex can be set up to contain standards that reveal an absolute concentration of viral RNA. Given how viral RNA concentrations are central data to the conclusions in this work, I believe that reporting the absolute concentration of viral RNA is important. Additionally, this will make the observations here more replicable across labs and viral RNA detection techniques. R: We thank the reviewer for this observation and have included the conversion table with the corresponding formula in the supplementary materials (s.m.), table 1s of paragraph 4, in the second section, \"Extra sample processing and extra data. » The total turn around time was around 4 h. Luminex detection was reported in arbitrary units given in accordance with Florida et al. (4 in s.m. and 11 here) (Line 63-64 s.m. and 265-269 s.m.) Regarding the reported viral RNA concentrations, it is unclear what the specificity, sensitivity, and detection range of the Luminex assay are as carried out by the authors. Therefore, I recommend the authors include relevant controls to estimate these. Reporting this information along with their experiments will add important validity and context to the data. R: More details have been included in the supplementary materials (s.m.), paragraph 6 of the first part of Materials and Methods: \"Luminex technology (Life Technology, USA) (ref. 3 in s.m. and 12 here,) was used to detect the viral RNA load in bacterial cultures. The detection was performed by using NxTAG® CoV Extended Panel, a real-time reverse transcriptase PCR assay detecting three SARS-CoV-2 genes on the NxTAG-enabled System MAGPIX® instrument, and the AccuPlex™ SARS-CoV-2 Reference Material Kit (SeraCare) as reference standard with sequences from the SARS-CoV-2 genome.\" Fig 3 is missing key controls. Recommend including a control of uninfected bacteria from a healthy donor stained with both α-SARS-CoV-2 nucleocapsid protein antibody and α-Gram-positive.bacteria antibody. R: We agree with the reviewer that controls, in general, are essential. That's why it seemed, first of all, absurd to us that no researcher had designed tests to check for interactions between coronaviruses and prokaryotic cells. This is why we emphasized that it is important to do different tests with different methods so that each is a control of the other, and that is what we did in Brogna et. al (2) and repeat in the supplementary materials, now added. For the required control with fluorescence vision of gram+ bacteria and lack of fluorescence for viral proteins in question, a sample of stool from an healthy 18-month-old child, checked negative by molecular testing, with healthy parents and never ill with SARS-CoV-2 at the time of collection, was used. This choice, a child's faeces, was made because, after two years of the pandemic, it is very difficult to find uninfected or asymptomatic carriers. However, as usual, we had not put in the panels in Figure 3 such control though we had done so. We thought the evidence in panel E of figure 3 would be sufficient. However, the reviewer's suggestion is valuable, and we add the required control (figure 3 panels F and G)and comment on it below: A panel (F, G) was added with the required control, a culture of only bacteria from the feces of a healthy individual, an 18-month-old child to be exact. The sample was obtained with the consent of both parents. As can be seen, only gram+ bacteria are highlighted by fluorescence, although both primary antibodies have been included, both to gram+ and to the nucleocapsid protein of SARS-CoV-2. The sentence \"... and panels F and G show a group of gram+ bacteria by fluorescence, derived from the stool bacteria culture of a healthy 18-month-old child (with healthy parents and never ill with SARS-CoV-2 at the time of collection and with and with their written consent) negative to molecular test to SARS-CoV-2, although the other primary antibody to the nucleocapsid protein is also included and does not show a red signal\". Line 193-199 The authors conclude from the microscopy data that fecal bacteria are infected by SARS-CoV-2 in samples collected on day 30 from an adult patient, am1. Notably, this patient, along with the others in the study was prescribed probiotics with two Gram-positive bacteria (Lactobacillus reuteri and Bacillus clausii) in their diets for 30 days prior to sample collection. In the event that bacteria are in fact infected by SARS-CoV-2, it is unclear if this is an artefact of the probiotic supplements and treatment regime. R: We apologize to the reviewer if we are not clear. The Luminex data at day 60 refer to subsequent stool sampling from family members, whereas the microscope images are from bacteria culture of the am1 sample taken at time zero and cultured, as detailed in the supplementary materials, for 30 days in the laboratory. In addition, the probiotic legend was included because it is required by the case series checklist guidelines but should not be understood as an indication of possible therapy. The use of probiotics was used only as an aid in view of the fact that all the literature now agrees that SARS-CoV-2-induced alteration of bacterial flora occurs. The words « only as re-balancers of bacterial flora… » are added. Line101 e 127 I encourage the authors to provide more methodological information in the manuscript. As a matter of principle, manuscripts should in and of themselves provide sufficient information for readers to repeat experiments without having to go down the rabbit hole of chasing down references to other works. The current manuscript exhibits this concern that is prevalent in scientific publications. Some instances of this in the current manuscript include - “molecular testing for SARS-CoV-2 was performed by using Luminex technology as described by us previously” - It is unclear how the samples were prepared, if controls were included and what the parameters of this assay were. Methodology used to isolate and culture bacteria from stool - It is unclear how bacteria were isolated from stool. This is important information to get a sense of how rigorous this method was, whether there are inherent biases regarding what bacteria are favored in the culturing process and if there are chances for other residual contaminants from the fecal sample. Methodology used to collect and preserve stool samples - the majority of existing reports are unable to culture viable SARS-CoV-2 from fecal samples, even when the samples are preserved in Viral Transport Media (VTM). Therefore, clarity about how the current work collected and preserved samples are crucial to understanding how they have been successful at recovering viable viral particles. R: We thank the reviewer for this valuable advice and apologize because it was not our intention to direct him to read our other work, but unfortunately, as the manuscript is set up as a case series, we had a predetermined number of words and checklist guidelines to follow. To overcome this problem, we suggested that he read our other papers, but the reviewer rightly asked for more details, and we have summarized the materials and methods of our other studies in the supplementary materials (s.m.) now attached. Of course, the words are in italics because we are reporting exactly what we have already published, with author’s permission. Please forgive the reviewer if we take the liberty to give some advice, since this is an open review, to anyone who would like to start repeating or improving the published experiments. Virus (SARS-CoV-2)-positive stool samples can be stored at 4°C in a previously sterile container as soon as they are collected from the patient. Culture in a multipotent medium, performed to grow only bacterial cells and exclude other eukaryotic cells, started after the homogenization and inorganic debris removal procedures, is best performed within 24 to 48 hours. Therefore, good timing between clinical collection and processing in the appropriate laboratory is important. In addition, freezing the samples, although it results in the preservation of proteins and nucleic acids, ruins the viability of bacteria. Variations to the presented methodology can be made, or protein expression can be assessed by other methods and quantified over time. Our humble opinion suggests that the genetic part should always be verified with the actual protein expression and ultimately with the microscopic view of the viral particle. Integration of data ( genetic, proteomic, microscopy) is essential to observe typical or atypical viral behaviour. Minor suggestions: Request citation and clarity on the statement - “several studies have reported….intestinal bacterial co-infection in COVID-19 patients”. R : we have added the references 9-11 (line 20) : Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DS, Chow KM, Ng SSS, Li TC, Ng RW, Yip TC, Wong GL, Chan FK, Wong CK, Chan PK, Ng SC. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021 Apr;70(4):698-706. doi: 10.1136/gutjnl-2020-323020. Epub 2021 Jan 11. PMID: 33431578; PMCID: PMC7804842; Yamamoto S, Saito M, Tamura A, Prawisuda D, Mizutani T, Yotsuyanagi H. The human microbiome and COVID-19: A systematic review. PLoS One. 2021 Jun 23;16(6):e0253293. doi: 10.1371/journal.pone.0253293. PMID: 34161373; PMCID: PMC8221462 ; Wang, B., Zhang, L., Wang, Y. et al. Alterations in microbiota of patients with COVID-19: potential mechanisms and therapeutic interventions. Sig Transduct Target Ther 7, 143 (2022). https://doi.org/10.1038/s41392-022-00986-0) Request citation and clarity on the statement - “Observations of possible links between the animal gut microbial environment and coronaviruses have been reported over time”. The current citations do not have evidence for a possible link to the gut microbial environment. R : We have refreshed the final part of the phrases in : « in some studies,» and we have added the references 16-20 (Line 31): Li HY, Li BX, Liang QQ, Jin XH, Tang L, Ding QW, Wang ZX, Wei ZY (2020) Porcine deltacoronavirus infection alters bacterial communities in the colon and feces of neonatal piglets. Microbiologyopen 9:e1036 ; Felten S, Klein-Richers U, Unterer S, Bergmann M, Leutenegger CM, Pantchev N, Balzer J, Zablotski Y, Hofmann-Lehmann R, Hartmann K. Role of Feline Coronavirus as Contributor to Diarrhea in Cats from Breeding Catteries. Viruses. 2022 Apr 21;14(5):858. doi: 10.3390/v14050858. PMID: 35632600; PMCID: PMC9143444 ; Meazzi S, Stranieri A, Lauzi S, Bonsembiante F, Ferro S, Paltrinieri S, Giordano A. Feline gut microbiota composition in association with feline coronavirus infection : A pilot study. Res Vet Sci. 2019 Aug ;125 :272-278. Doi : 10.1016/j.rvsc.2019.07.003. Epub 2019 Jul 9. PMID : 31326703 ; PMCID : PMC7111766. ; Storz J, Lin X, Purdy CW, Chouljenko VN, Kousoulas KG, Enright FM, Gilmore WC, Briggs RE, Loan RW. Coronavirus and Pasteurella infections in bovine shipping fever pneumonia and Evans' criteria for causation. J Clin Microbiol. 2000 Sep;38(9):3291-8. doi: 10.1128/JCM.38.9.3291-3298.2000. PMID: 10970373; PMCID: PMC87376; Saif LJ. Bovine respiratory coronavirus. Vet Clin North Am Food Anim Pract. 2010 Jul;26(2):349-64. doi: 10.1016/j.cvfa.2010.04.005. PMID: 20619189; PMCID: PMC4094360) Fig 1 reports “Viral load” although what is actually reported is the viral RNA concentration, which can be different from viral load because not all viral particles are lysed and provide RNA for detection, and some viral RNA is reported to come from non-viral reservoirs4. R : We have nothing to add to this reviewer's comment because we are in perfect agreement. The authors of reference 4 (Alexandersen et al.), clarify that nasopharyngeal samples contain subgenomic sequences of SARS-CoV-2. Textually they write: 'The results described here fully support that SARS-CoV-2 genomic and subgenomic RNAs are present in diagnostic samples even in late infection/after active infection' and 'The detection of subgenomic RNA is therefore not direct evidence of active infection instead its presence at lower levels than virion genomic RNA results in detection for a shorter period of time unless using, e.g., highly sensitive NGS'. Similarly, in the tables presented in figure 1, we do not want to indicate who among the family members in the presented case series is infectious or not because the story in the paper describes well that they are all asymptomatic, except for the little girl. In the paper, we never speculate on the correlation between viral charge and high infectivity. The tables only show how with the passage of a fairly long time (figure 1 C and D), 60 days, the presence of traces of viral RNA is no longer detected, in agreement with many contemporary studies. It should also be pointed out that reference 4, Alexandersen et al., describes the nasopharyngeal sampling as a viral RNA collection event, and readers and scientists should reflect that the sampling is performed on mucous membranes that are overabundant with bacteria and that it cannot be excluded that subgenomic sequences in non-SARS-CoV-2 sufferers could have bacteria, also, as a reservoir. We do not associate the viral load to the disease state, nor do we speculate on high viral replication and high infectivity. Viral load is now a usual term used in scientific work, and the accuracy of the reviewer is relevant, but at this point, should specify the wording of many of the works currently published. However, we corrected everywhere the legend of figure 1 and other phrases in “RNA viral Concentration.” The manuscript calls for major editorial revisions given numerous improper usages of phrases. For instance - a) There are no “fecal-oral bacteria”, which suggests specific bacteria in the feces are able to be transmitted orally. b) It is unclear what “Bacterial feces” means. c) “RNA viral load count” appears miswritten. R : a) we apologize to the reviewer. We want to say bacteria from the gastrointestinal tract, and we replaced the phrase with \"bacteria of the human gut microbiome.\" b) The sentence was rewritten: « The feces of this patient was cultured in bacterial culture media and after 30 days, the pellet of bacteria, have been analyzed by TEM, immune-EM, and by fluorescence microscopy, and a set of obtained images is shown in Figure 2 ( for more details see supplementary material-s.m.)». Line 133-136 c) The word count is a typo, and we followed the reviewer’s suggestion and pointed out that it is RNA concentration Additional notes: I don’t have experience with interpreting TEM images and therefore leave this comment here rather than as a cause for major revision. TEM images are complex requiring the appropriate collection and processing of samples, the inclusion of controls, and careful interpretation of observations. The improper use of EM to study SARS-CoV-2 from tissue samples has been a cause for concern5,6. To my untrained eye, Fig 2 seems to be another example of misinterpreted EM data because - If Fig 2a in fact displays SARS-CoV-2 viral particles inside a bacterium, it is surprising to me that the bacterial host appears to be entirely filled by viral particles with no room for its essential, native molecules. To me, this figure seems like that of the widely described multivesicular bodies that are unrelated to SARS-CoV-2 and yet regularly misinterpreted6. The figures don’t appear to have sufficient resolution to highlight the ultrastructures typical of SARS-CoV-2 that are required to unmistakable identify viral particles5. If Fig 2b in fact presents the case of a bacteria with viral particles around it, it merely appears like viral particles proximal to the bacteria in this image, with no evidence that these viruses in fact infected the bacteria. The conclusion that viral particles are found in the extracellular matrix of gut bacteria is an over-reach without sufficient evidence. R: We thank the reviewer for finally raising the same issue as the public comment to the present manuscript left by Dr.Michael Laue. We will disregard the fact that he states that he is not an expert in electron microscopy but we respectfully respond to his objections: The article by Dittmayer and Laue et al. (5) that both we cite in the text of the manuscript and the reviewer cites in support of the misinterpretations that can be made during sample processing and during the interpretation of viral particles should be clarified that the authors emphasize the importance of matching, i.e., associating the EM image with genetics as well, attesting to the presence of the viral pathogen of interest or vice-versa. They are the ones who make it clear that imaging must be supported by genetic or protein testing, and in fact, they quote exactly that: “…the presence of SARS-CoV-2 particles (figure A-D EM) complements the molecular traces of SARS-CoV-2s pecific proteins or nucleic acids”. Our study demonstrated exactly that: EM images of virus-like particles combined with genetic confirmation of the presence of SARS-CoV-2, immunofluorescence microscopy with antibodies, and other tests, now described in the supplementary materials (s.m.). The addition of immunofluorescence images highlighting both GRAM+ bacteria and fluorescence of the nucleocapsid protein of SARS-CoV-2 is also important. However, as a final note, we have added in the supplementary materials (s.m.) many other evidences, including that of nitrogen isotope, added to the culture medium, which marks the proteins of SARS-CoV-2 (2) and lays a stable stone to our experiments. With due respect to the reviewer, it should be noted that citation #6 (Calomeni E. et al.), taking as a reference to highlight how SARS-CoV-2 particles can be confused with multivesicular bodies, states the following: \"MVBs were always been identified in podocytes (1 to 4 podocytes per glomerulus), but we have not seen them in tubular epithelial cells. MVBs were occasionally observed in endothelial cells (mainly arterial or arteriolar) and in a parietal glomerular epithelial cell of biopsy. MVBs theoretically may represent podocyte endocytosis with subsequent formation of intracytoplasmic microvesicles resembling viruses.\" ......\" However, microvesicles are commonly \"free-floating\" in the cytoplasm of many cell types, including tubular epithelial cells.\"............\" caution is suggested when identifying a virus by EM in tissue sections.\" In other words, MVBs are typical formations in animal tissues, not found in bacterial cultures. They cannot be confused with viral particles that we show in bacterial cultures even light-years away. They are by no definition at all associable with the viral particles we show in Figure 2A and 2B. They are completely different situations and two different substrates so there is really no basis for confusing the viral particles we show with the MVB. It was made clear in the text that the images are from a 30-day culture of prokaryotic cells, bacteria, and that there are no mammalian cells; furthermore, Figure 2B, even for a non-expert in microscopy, cannot be misunderstood as it is an image showing a bacterial lysis phase with viral particles around it. In the work of Bullock et al., (13) cited in the comment by Dr. Laue just in Figures 1C and 2C, are clearly visible viral particles indicated by the authors as coronavirus particles perfectly identical to those we show inside the bacterium in our Figure 2A and around the lysed bacterium in Figure 2B. Moreover, the authors cite the following sentence to demonstrate that the protein spike, unless a special preparation with tannic acid is used, is almost never visible in microscopic images as they report:\" (ii) Coronaviruses do have projections on the surface; however, in thin sections, the \"spikes\" on the outside are not always (indeed, not usually) clearly visible, unless specially stained (e.g., with tannic acid). They may or may not appear as a very short 'fuzz.'\" The ribonucleoprotein, with all due respect and contrary to Dr. Laue's comments, is clearly visible, just like that shown in the works of Dittmayer, Laue, et al. (5), and Bullock et al. (13). The Aurion particles of 10 nm may overlap, but in the supplementary materials (s.m.), we show Figure 2s where the same test was repeated with the pre-ebbending technique in another facility and also satisfies this aspect challenged in the comments. (line 176- 194s.m.). With due respect to the reviewer, all supporting data, including those added in the supplementary materials, dispel doubts shown, and it is still worth noting that the evidence of the nitrogen radioisotope found in the viral proteins after adding the element in the 30-day bacterial culture dispels all doubt. The data should be integrated and analyzed together, and not considered individually. The figure is missing controls such as stained and unstained images of comparable bacteria without the presence of the alleged SARS-CoV-2 viral particles. Given these observations and the importance of this figure to the central tenet of this manuscript, I recommend the editorial team seeks input from an expert in TEM. R : In Image 3, we added panels F and G with only controls on gram+ bacteria in the absence of SARS-CoV-2. The objections made by the reviewer seem identical to those in the commentary by Dr. Michael Laue, an imaging expert. Responding to the reviewer, we also questioned Dr. Michael Laue's objections. We remind the reviewer that these are the first images of coronavirus in bacterial cultures. There are no other comparisons in the current literature, so any speculation on the present manuscript finds as debate the serious shortcoming of the failure to control infectivity first on prokaryotic cells, which are much more abundant above the epithelial layer where virus-receptor interaction takes place. What should be done before proclaiming for certain and establishing some possible pathogenetic mechanisms of infectivity, i.e., some possible viral protein and epithelial cell receptor binding interactions, is the control between coronaviruses in particular but also other RNA viruses in general and bacterial cells, much more abundant, it bears repeating, within the human microbiome. Moreover, even if an interaction does not take place, control also over bacterial metabolism and what they produce (2,14) in the presence of a novel viral pathogen should in no way be excluded. This, too, is a serious deficiency in possible controls. The hypothesis that SARS-CoV-2 may infect bacteria is both biologically fascinating and clinically highly relevant. R: We apologize to the reviewer: but with due respect: it is no longer a hypothesis but new observations (ref 2,14, 15). We thank the reviewer for giving us an opportunity to engage in constructive scientific debate and to improve the present paper by highlighting what he thought was right and by improving what he thought was appropriate. This is because there are no examples that I know of or can find of viruses that affect humans that can also retain the molecular machinery to affect bacterial cells. Therefore, the idea that this is possible is biologically fascinating and can pave the path to many follow-up studies. Further, SARS-CoV-2 continues to be a major threat, having claimed over 6 million people worldwide. Therefore, careful evaluation of the potential sources of future outbreaks is critical from a personal and public health standpoint. If in fact bacteria in the gut can harbor infectious SARS-CoV-2 viruses, this adds to another dimension of the COVID-19 pandemic that calls for urgent precautionary measures. Unfortunately, the current manuscript is missing many controls and methodological details, and has insufficient data to make the case that bacteria are in fact infected by SARS-CoV-2. Given the hugely significant impact that concluding gut bacteria can be infected by SARS-CoV-2 through a bacteriophage-like property can have to humanity, I encourage the authors and editorial team to exercise caution and responsibility in promoting this conclusion with insufficient evidence. R : We believe that the reviewer now has much more clarification, but may notice more information about the concepts laid out and the importance of doing the checks between viruses and bacteria, to avoid epidemiologically and pathogenic misdiagnoses in the article under review also on F1000--Petrillo M, Querci M, Brogna C et al. Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 1; peer review: awaiting peer review]. F1000Research 2022, 11:292 (https://doi.org/10.12688/f1000research.109236.1) References Petrillo M, Brogna C, Cristoni S, Querci M, et al.: Increase of SARS-CoV-2 RNA load in faecal samples prompts for rethinking of SARS-CoV-2 biology and COVID-19 epidemiology.F1000Res. 2021; 10: 370 PubMed Abstract | Publisher Full Text Brogna C, Brogna B, Bisaccia DR, Lauritano F, et al.: Could SARS-CoV-2 Have Bacteriophage Behavior or Induce the Activity of Other Bacteriophages?. Vaccines (Basel). 2022; 10 (5). PubMed Abstract | Publisher Full Text Pedersen R, Tornby D, Bang L, Madsen L, et al.: Rectally shed SARS-CoV-2 lacks infectivity: time to rethink faecal–oral transmission?. Nature Reviews Gastroenterology & Hepatology. 2021; 18 (9). Publisher Full Text Alexandersen S, Chamings A, Bhatta T: SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication. Nature Communications. 2020; 11 (1). Publisher Full Text Dittmayer C, Meinhardt J, Radbruch H, Radke J, et al.: Why misinterpretation of electron micrographs in SARS-CoV-2-infected tissue goes viral. The Lancet. 2020; 396 (10260): e64-e65 Publisher Full Text Calomeni E, Satoskar A, Ayoub I, Brodsky S, et al.: Multivesicular bodies mimicking SARS-CoV-2 in patients without COVID-19. Kidney International. 2020; 98 (1): 233-234 Publisher Full Text Guo M, Tao W, Flavell RA, Zhu S. Potential intestinal infection and faecal-oral transmission of SARS-CoV-2. Nat. Rev. Gastroenterol. Hepatol. 2021;18:269-283. doi: 10.1038/s41575-021-00416-6. Guo M, Tao W, Flavell RA, Zhu S. Reply to: Rectally shed SARS-CoV-2 lacks infectivity: time to rethink faecal-oral transmission? Nat Rev Gastroenterol Hepatol. 2021 Sep;18(9):669-670. doi: 10.1038/s41575-021-00503-8. PMID: 34312525; PMCID: PMC8311630 Zhou, P., Yang, XL., Wang, XG. et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579, 270-273 (2020). https://doi.org/10.1038/s41586-020-2012-7 Stone R. A new killer virus in China? Science. (2014). Available online at: https://www.sciencemag.org/news/2014/03/new-killer-virus-china Floridia, M. & Cristoni, S. PROSAD: A powerful platform for instrument calibration and quantification. Rapid Commun. Mass Spectrom. 2014. doi: https://doi.org/10.1002/rcm.6808.): ARB= [Σ(SI*NF*COF)/ Σ (NF*COF)] where SI: Signal intensity converted to Counts/s; NF: Noise Factor; COF: Correction Factor Dunbar SA. Applications of Luminex xMAP technology for rapid, high-throughput multiplexed nucleic acid detection. Clin Chim Acta. 2006. doi: https://10.1016/j.cccn.2005.06.023 Bullock HA, Goldsmith CS, Miller SE. Best practices for correctly identifying coronavirus by transmission electron microscopy. Kidney Int. 2021 Apr;99(4):824-827. doi: 10.1016/j.kint.2021.01.004. Epub 2021 Jan 22. PMID: 33493525; PMCID: PMC7825881 Brogna C, Cristoni S, Petrillo M, Querci M, Piazza O, Van den Eede G. Toxin-like peptides in plasma, urine and faecal samples from COVID-19 patients. F1000Res. 2021;10:550. Published 2021 Jul 8. doi:10.12688/f1000research.54306.2 Petrillo M, Querci M, Brogna C et al. Evidence of SARS-CoV-2 bacteriophage potential in human gut microbiota [version 1; peer review: awaiting peer review]. F1000Research 2022, 11:292 (https://doi.org/10.12688/f1000research.109236.1)"
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https://f1000research.com/articles/11-135
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https://f1000research.com/articles/13-1239/v1
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16 Oct 24
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{
"type": "Research Article",
"title": "A Cross-Sectional Study on Key Factors of Burnout Among Tunisian Oncology Nurses",
"authors": [
"ines Ben Safta",
"Feten Fekih Romdhane",
"Maher Slimane",
"Ben Dhiab Tarek",
"Feten Fekih Romdhane",
"Maher Slimane",
"Ben Dhiab Tarek"
],
"abstract": "Background Nurses play an essential role in patient care, and nurse-patient relationship are a fundamental aspect of healthcare delivery. Research has indicated that oncology nurses are particularly susceptible to burnout. However, there is limited research on nurse burnout in oncology, particularly in the Arab Muslim world.\n\nObjective This study aimed to investigate burnout among oncology nurses and analyze its association with professional and sociodemographic factors.\n\nMethods A cross-sectional study was conducted with oncology nurses at the Salah Azaiz Institute. We assessed socio-demographic data, work variables, job satisfaction, and burnout using the Maslach Burnout Inventory.\n\nResults Of the nurses surveyed, 78 responded correctly to the questionnaire. The median age of participants was 37 years, with a predominance of females (52.6%). The median duration of oncology work was 11 years. Regarding job satisfaction, 30.8% were somewhat dissatisfied, and 24.4% were not satisfied. The prevalence of burnout was 89.9%, with 73.1% experiencing high levels of emotional exhaustion, 48.7% high levels of depersonalization, and 25.6% a low level of personal accomplishment. Personal medical and psychiatric history, along with job satisfaction, emerged as the strongest predictors of burnout in the multivariate analysis.\n\nConclusion This study highlights the significant prevalence of burnout among nurses in oncology settings. In Tunisia, there is an urgent need to prioritize the psychological well-being of oncology nurses. Preventive strategies should emphasize enhancing working conditions to reduce these risks.",
"keywords": [
"Burnout",
"Oncology",
"Nurses",
"Oncology nurses",
"Job satisfaction"
],
"content": "1. Introduction\n\nThe role of nurses in oncology is essential, with a significant amount of time spent in relational care, making the nurse-patient relationship a cornerstone of patient care. As described by Orlando et al. (1958), the relationship between a patient and a nurse in a meeting is a dynamic ‘whole’ and each time unique.1 No specific personality traits were identified as predisposing factors for burnout. However, a variety of elements can precipitate its development, including: underlying motivations for selecting a career, resilience in facing occupational difficulties, an overly idealistic view of one’s profession, insufficient acknowledgment in the workplace, and a lack of prospects for career advancement.2\n\nBurnout, while not a disease, is a transitional syndrome frequently associated with specific circumstances, especially in high-stress specialties such as oncology.3 Nurses in this field face unique challenges, including dealing with critically ill patients, emotional workplace stress, caregiving burden, and patient mortality, leading to diminished empathic behavior towards patients.4 This not only threatens care quality but also impacts the survival of healthcare institutions.3 The consequences of burnout include reduced professional efficacy, reduced quality of life, mood alterations, anxiety, irritability, depression, suicidal ideation, and increased work absenteeism.5 Furthermore, some authors have reported that the repercussions of burnout are predominantly characterized by addictive behaviors and suicidal ideation.6\n\nTherefore, early prevention and diagnosis of burnout early are essential. It has been observed that when sufficient resources are available and there is effective collaboration among staff members within a unit, the perception of burnout decreased.7\n\nThis study aimed to explore burnout among oncology nurses and, examine its relationship with occupational and socio-demographic factors, particularly in the under-researched context of the Arab Muslim world.\n\n\n2. Methods\n\nThis descriptive cross-sectional study was conducted over one month, from April 15 to May 15, 2018, at the Salah Azaiez Institute (ISA) in four departments: cancer surgery, otorhinolaryngology, medical oncology, and radiotherapy. Eligible nurses had at least one year of oncology experience and sufficient French proficiency to complete the questionnaire. The exclusion criteria were nurses in training, those with administrative roles or without direct patient contact, those with a first-degree relative with cancer, and those suffering from a severe, disabling somatic condition (including cancer). Nurses with incomplete questionnaire responses or thise who withdrew their consent were also excluded.\n\nData were collected using an anonymous form that gathered socio-demographic and occupational information Table I (Extended data).8 Burnout was assessed using the Maslach Burnout Inventory (MBI), a tool developed by Maslach and Jackson in 1981.9 For this study, a copyright license was obtained to authorize the use of this proprietary instrument. The MBI evaluates three key dimensions of burnout: Emotional Exhaustion (EE), Depersonalization (DP), and Loss of Personal Achievement (PA). Burnout diagnosis was based on MBI scores exceeding Maslach’s defined thresholds in any of the three components.10 We categorized burnout into three levels: no, full, and intermediate.8\n\nThis study was conducted in accordance with the ethical standards outlined in the Declaration of Helsinki. Ethical approval was obtained from the Institutional Review Board (IRB) of the Salah Azaiez Institute, with the approval reference number ISA/2024/01. The committee approved the study on 30 January 2024, ensuring strict adherence to ethical guidelines and the protection of participants’ rights and confidentiality throughout the research process\n\nData analysis was performed using SPSS software (version 23.0, IBM Corp). Continuous variables were tested for normal distribution using the Shapiro-Wilks test. Owing to significant deviations from the normal distribution, medians, interquartile ranges, and extreme values were calculated for quantitative variables. Group differences for continuous variables were analyzed using Mann-Whitney or Kruskal-Wallis tests, and percentages were compared using Fisher’s exact test. The Spearman correlation coefficient was used to examine associations between quantitative variables, considering p < 0.05 as indicative of correlation. Multiple linear regression identified independent predictors of EE, DP, and PA, with the significance level set at 0.05. Please refer to the relevant underlying data.8\n\n\n3. Results\n\nAmong 139 nurses working at the institute, 78 provided complete responses to the questionnaire. The selection process for the participants is shown in Figure 1.\n\nThe socio-demographic characteristics of our study population are detailed in the extended data.8 The sample predominantly consisted of female nurses (52.6%, n=41), with a sex ratio of 0.9.\n\nSignificantly, 35.9% (n=28) of the nurses had a medical history of cardiovascular or endocrine diseases, and 23.1% (n=18) reported a psychiatric history of anxiodepressive disorders. Psychotropic drug use in the past year was reported by 17.9% (n=14) of nurses, including antidepressants (11.5%, n=9), anxiolytics (2 cases), and hypnotics (3 cases).\n\nA significant 89.9% (n=70) of the nurses experienced burnout, as indicated by the severe levels in at least one sub-dimension of the Maslach Burnout Inventory (MBI). A detailed analysis revealed that all nurses included in the study were affected by burnout to some degree, with 46.2% (n=36) exhibiting high levels on at least one burnout subscale.\n\nThe results of the univariate analysis results are presented in Table II (Extended data).8 A multivariate multiple linear regression was conducted, incorporating the variables most correlated with Emotional Exhaustion (EE), Depersonalization (DP), and Personal Achievement (PA), as shown in Table III. This analysis identified personal psychiatric history and job satisfaction as the major predictors of EE. Job satisfaction has also emerged as a principal independent predictor of PA.\n\n\n4. Discussion\n\nOur findings corroborate the widely reported high prevalence of burn out among oncology nurses, emphasizing that job satisfaction is a primary predictor of EE and PA.\n\nOur study identified a substantial burnout rate (89.9%) among nurses. In the literature, the comparison between different burnout levels in oncology nurses in published series remains difficult. Indeed, so far there is no clear and precise consensus on two essential points: the precise definition of burnout as a syndrome, and the interpretation of the obtained scores in each of the three dimensions. Moreover, the majority of studies on burnout in oncology comprised all caregivers (doctors, nurses and assistant nurses); the published results were heterogeneous.\n\nIn the studies that defined burnout as the elevation of one of the three dimensions of the MBI, our results were quite comparable to the literature data.\n\nA French study conducted in 2008 among caregivers in oncology showed that 39% of the studied population was affected by burnout with predominance among doctors (38%), followed by assistant nurses (35.2%) and nurses (25%) 18.11\n\nA study conducted in 2010 in Italy compared the burnout levels among Oncology nurses (59 nurses working in the oncology units at the hospital and 33 at hospices, and found a higher level of burnout among nurses working at the Hospital.12\n\nFor other authors, burnout was defined by a high level of EE.\n\nIn a study published in 2005, American authors studied burnout among 305 nurses in Oncology, and found a high level of EE in 39% of cases.13\n\nA multicenter Chinese study published in 2013 including 708 nurses working in Oncology showed that 36.8% of the study population had high levels of burnout.14\n\nIn other works, the burnout was retained in the presence whether high levels of EE and DP, or a low level of PA.\n\nIn a Swedish multicenter study conducted in 2015 including 7412 nurses, the authors compared nurses according to their assignment services: a first group of nurses working in services and treating cancer patients (80% of treated patients, n = 1440) and a second group with a lower number of cancer patients (10-70% of treated patients, n = 5972).15 The authors identified a burnout rate of 22.8% in the first group versus 25% in the second one.\n\nOther authors retained a burnout syndrome in the presence of an alteration of the three dimensions of the MBI scale (high levels of EE and DP, and a low level of PA).\n\nAfter applying this definition, an Iranian study published in 2017 on 67 nurses working in oncology found a burnout rate of 38.8%.16\n\nThe results of a meta-analysis published in 2018, including 17 studies of which 82.3% were cross-sectional and using the MBI scale to assess the levels of burnout among oncology nurses17 found high scores of EE and DP in 30% and 15% of the cases, respectively, and low PA scores in 35% of cases.\n\nThe concept of burnout in Arab Muslim countries has not been well explored. A Tunisian study published in 2014, that assessed 60 nurses caring for end-of-life patients, revealed a burnout prevalence of 70%. Notably, 81.7% of participants exhibited high levels of burnout. Among them, 80% experienced a high level of emotional exhaustion, 70% reported a high level of depersonalization, and 17% demonstrated a low sense of personal accomplishment.18\n\nOther studies conducted in some countries such as Algeria and Saudi Arabia showed that nurses, in these countries, suffered from Burnout.19,20 A Jordanian study conducted among 181 psychiatric nurses found high levels of EE and DP in 32.7% and 27.7% of cases, respectively, and low levels of AP in 16.8% of cases).21 In a systematic review assessing burnout among healthcare professionals in Arabic countries, the authors recorded high EE (81.0%), high DP (80.0%), and low PA (85.8%).22\n\nIn our study, we found an association between high EE levels and female sex.\n\nIn the literature, the role of sex in the occurrence of burnout remains unclear. According to a meta-analysis published in 2010 that analyzed 183 studies, women were more emotionally exhausted than men, while men had higher levels of depersonalization than women.23\n\nThe results of a Norwegian study published in 2011 also suggested that female nurses exerienced more burnout than male nurses (especially higher levels of EE).24 An American study of all caregivers in oncology showed that men had a greater sense of PA than women.25\n\nA greater prevalence of burnout among women was explained by greater involvement in the emotional relationship with their patients as well as more difficulties in reconciling their professional and family lives.26 Therefore, Burnout tend to be more common among women because of more important life roles (housework and childcare) and work–family conflict.\n\nWe found that younger age was associated with lower AP levels. According to Maslach and Goldberg,27 the older one gets, the more adaptive mechanisms against stress are improved. For Ullrich and FitzGerald,28 young oncology health professionals would have more difficulties communicating with their patients, would be more stressed at work, and would express more criticism at work.\n\nSome authors have explained this fact by three points: (1) experience and capacity of adaptation (coping strategies) improves with age; (2) distancing from many factors of stress occurs with age, and (3) more dissatisfied nurses would leave at a young age.29\n\nIn our study, we did not find statistically significant associations between burnout and other socio-demographic factors (marital status, number of children, habitat type and socio-economic level).\n\nThese results match the majority of studies published on the burnout in the literature.30,31\n\nHowever, some authors have suggested that having a partner and children is a protective factor against burnout.31 Maslach and Jackson32 found that individuals without children are more likely to experience burnout. Another study showed that having children is correlated with the occurrence of EE.33\n\nIn our study, a high DP level was significantly associated with the presence of a medical history. In a publication dealing with the assessment of burnout among 67 nurses in oncology, Quattrin et al. found a statistically significant association between personal medical history and the severity of burnout.33 The study showed that EE was correlated with the presence of a medical surgical personal history and the experience of having a family member affected by cancer.\n\nThis study showed a statistically significant association between the level of high EE and the presence of a personal psychiatric history, taking psychotropic drugs in the last year and asking for psychological help because of work exhaustion.\n\nThis association has been previously described in the literature. Catt and al.34 found a psychiatric comorbidity associated with burnout in 5-27% of cases in 10 carcinology teams in England. For example, n Italy, Bressi et al. reported a 28.8% prevalence of psychiatric disorders among oncology nurses.35 The authors also found a statistically significant association between psychiatric morbidity and the three dimensions of burnout. Finally, in a literature review burnout among caregivers in oncology was found to be associated with somatic, psychological and behavioral disorders.36\n\nIn our population, lack of leisure activities (sports, music, etc.) was associated with EE. Leisure and social extra-professional activities would play an important role in easing and tension stress. Quattrin and al. showed that the different strategies adopted by oncology nurses to manage stress (physical activity, medical examinations, no conventional strategies to manage stress, healthy eating behaviors, rest, healthy lifestyle and hobbies) were associated with a reduction in EE levels.33\n\nIn addition, the fact that not knowing or not being able to take time to relax has been mentioned in several publications as being one of the first disturbance in burnout.36 In our study, tobacco and/or alcohol consumption did not correlated with the severity of the burnout.\n\nKash et al.25 found that the consumption of cigarettes, alcohol or drugs to relax is a predictor of EE and DP. In our study, the number of years worked in oncology was negatively correlated with a high level of DP.\n\nIn the literature, there is conflicting data on the relationship between burnout and professional experience.\n\nFor some authors, the more old a caregiver is in a team, the less they are at risk of burnout. Inexperienced caregivers would be made fragile and disappointed with the reality on the ground which is opposed to the ideals of the profession at the beginning of their career, while more experienced caregivers stood and went past this stage. On the other hand, prolonged exposure to suffering and difficult patients, and the accumulation of a significant workload without compensatory recognition could lead these experienced caregivers to exhaustion in the middle or at the end of their careers.\n\nIn our study, 55.2% of the nurses were somewhat unsatisfied or unsatisfied at work. A statistically significant association was found between high EE, low PA and dissatisfaction at work. In the multivariate analysis, lack of job satisfaction was found to be an independent predictor of increased EE and decreased PA scores.\n\nSome authors stated that poor job satisfaction would represent the roots of burnout; the causes would be chronic devaluation and insufficient recognition from the hierarchy, reflected by weak PA scores.37\n\nShang et al.14 found that lack of satisfaction was predictive of psychiatric illness and burnout. Gulalp and al.38 have shown that lack of job satisfaction is associated with the three dimensions of burnout.\n\nBressi et al. found that 10% of oncology nurses were not satisfied at work; this dissatisfaction was correlated with low levels of PA.35\n\nA Turkish study published in 2017 used the “Minnesota Job Satisfaction score” to determine the level of satisfaction of 129 nurses working in oncology, and found a negative and significant correlation between the burnout level measured by the MBI and the satisfaction score.39\n\nThe burnout of nurses was associated in the literature with psychiatric symptomatology manifesting itself through a loss of sleep, a feeling of stress, depression and dissatisfaction with daily activities.11 In addition, the burnout of caregivers lowers the quality of care, and influences the working conditions of health care providers.40 Burnout reduces satisfaction with work, involvement in the organization and performance. This increases the desire to change jobs as well as absenteeism. Even in his position, a caregiver suffering from burnout is less effective and therefore less productive in economic terms.41\n\nWhile his study, provide valuable insights into burnout among Tunisian oncology nurses, it has certain limitations. Firstly, the relatively small sample size necessitates caution when generalizing the results. Additionally, the study’s cross-sectional design limited our ability to draw conclusions about longitudinal changes or establish causal relationships between the variables studied and the level of nurse burnout. Future studies with larger samples across various oncology services in Tunisia are recommended to provide more comprehensive insights.\n\nThe findings of this study indicate a high prevalence of burnout among oncology nurses, which has significant clinical implications. The association between burnout and factors such as job satisfaction and personal psychiatric history highlights the need for targeted interventions. These could include mental health support, improved working conditions, and strategies for enhancing job satisfaction. Addressing these factors is essential for maintaining nurse’s well-being and ensuring the delivery of quality patient care in oncology settings.\n\n\n5. Conclusion\n\nThis study confirms that burnout is a significant issue among oncology nurses in Tunisia, with a notably high prevalence. This highlights the urgent need for measures to support the psychological well-being of healthcare professionals. Given the association between burnout and personal psychiatric history and job satisfaction, tailored strategies to improve working conditions and mental health support are essential.\n\n\nConsent\n\nAll participants were fully informed about the purpose of the study, and verbal consent was obtained before they completed the questionnaires. Written consent was not deemed necessary due to the non-invasive nature of the study. This approach was approved by the ethics committee, which granted a waiver for written consent. Only participants who provided verbal consent were included in the study.\n\n\nStatement of author roles/contributions to the manuscript\n\nAuthor Ines Ben Safta participated in the conceptualization, formal analysis and drafting the manuscript. Author Feten Fekih-Romdhane supervised study and helped draft the manuscript. Author Maher Slimane helped to draft the manuscript. Author Tarak Ben Dhiab validated the manuscript. All authors have read and approved the final manuscript.",
"appendix": "Data availability\n\nHarvard Dataverse: questionnaire burn out oncologic nurses english version, https://doi.org/10.7910/DVN/UXZJP2 8\n\nThis project contains the following underlying data:\n\n• Date file 1: burn out ENGLISH version.xlsx (anonymised underlying data collected from oncologic nurses)\n\nHarvard Dataverse: questionnaire burn out oncologic nurses english version, https://doi.org/10.7910/DVN/UXZJP2 8\n\nThis project contains the following extended data:\n\n• Questionnaire: questionnaire ENGLISH.docx\n\n• Sociodemographic data and univariate analysis.docx\n\nData are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication).\n\n\nAcknowledgments\n\nWe acknowledge the support provided by ChatGPT, an AI language model developed by OpenAI, for its valuable assistance in enhancing the clarity and coherence of the medical writing, as well as for the accurate translation of content from French into English. ChatGPT was utilized to streamline the writing process, and to facilitate the translation, preserving the scientific integrity of the original text while making it accessible to an English-speaking audience.\n\n\nReferences\n\nBilleter-Koponen S, Fredén L: Long-term stress, burnout and patient–nurse relations: qualitative interview study about nurses’ experiences. Scand. J. Caring Sci. 2005 Mar 1 [cited 2024 Jan 10]; 19(1): 20–27. PubMed Abstract | Publisher Full Text\n\nLe Barbier D : syndrome d’épuisement professionnel du soignant. Presse Med. 2004 Mar 1; 33(6): 394–399. PubMed Abstract | Publisher Full Text\n\nColombat P, Dauchy S, Machavoine JL: Le syndrome d’épuisement professionnel des soignants en oncologie et hématologie. Hematologie. 2015 Sep 1; 21(5): 280–288. Publisher Full Text\n\nWilkinson H, Whittington R, Perry L, et al.: Examining the relationship between burnout and empathy in healthcare professionals: A systematic review. Burn. Res. 2017 [cited 2024 Jan 13]; 6: 18–29. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEelen S, Bauwens S, Baillon C, et al.: The prevalence of burnout among oncology professionals: oncologists are at risk of developing burnout. Psychooncology. 2014 Dec 1 [cited 2024 Jan 13]; 23(12): 1415–1422. Reference Source\n\nMhamdi S, Nakhli MS, Kahloul M, et al.: Prévalence du burnout en milieu d’anesthésie réanimation dans le centre tunisien. PAMJ. 2018 [cited 2024 Jan 13]; 31(111). PubMed Abstract | Publisher Full Text | Free Full Text Reference Source\n\nRussell K: Perceptions of Burnout, Its Prevention, and Its Effect on Patient Care as Described by Oncology Nurses in the Hospital Setting.2016 Jan 1 [cited 2024 Jan 13]; 43(1): 103–109. Reference Source\n\nBen SI: questionnaire burn out oncologic nurses english version [Database]. Harvard Dataverse. 2024.\n\nMaslach C, Jackson SE: The measurement of experienced burnout. J. Organ. Behav. 1981 Apr 1 [cited 2024 Jan 13]; 2(2): 99–113. Publisher Full Text\n\nMaslach Burnout Inventory: Third edition.[cited 2024 Jan 13]. Reference Source\n\nLissandre S, Abbey-Huguenin H, Bonnin-Scaon S, et al.: Facteurs associés au burnout chez les soignants en oncohématologie. Oncologie. 2008 Feb 20 [cited 2024 Jan 13]; 10(2): 116–124. Publisher Full Text\n\nOstacoli L, Cavallo M, Zuffranieri M, et al.: Comparison of experienced burnout symptoms in specialist oncology nurses working in hospital oncology units or in hospices. Palliat. Support. Care. 2010 Dec [cited 2024 Jan 13]; 8(4): 427–432. Publisher Full Text Reference Source\n\nFriese CR: Nurse Practice Environments and Outcomes: Implications for Oncology Nursing.2005 Feb 8 [cited 2024 Jan 13]; 32(4): 765–72. Number 4/2005. Reference Source\n\nShang J, Friese CR, Wu E, et al.: Nursing Practice Environment and Outcomes for Oncology Nursing. Cancer Nurs. 2013 May [cited 2024 Jan 13]; 36(3): 206–212. PubMed Abstract | Publisher Full Text | Free Full Text\n\nLagerlund M, Sharp L, Lindqvist R, et al.: Intention to leave the workplace among nurses working with cancer patients in acute care hospitals in Sweden. Eur. J. Oncol. Nurs. 2015 Dec 1; 19(6): 629–637. PubMed Abstract | Publisher Full Text\n\nTaleghani F, Ashouri E, Saburi M: Empathy, Burnout, Demographic Variables and their Relationships in Oncology Nurses. Iran. J. Nurs. Midwifery Res. 2017; 22(1): 41–45. PubMed Abstract | Publisher Full Text\n\nCañadas-De la Fuente GA, Gómez-Urquiza JL, Ortega-Campos EM, et al.: Prevalence of burnout syndrome in oncology nursing: A meta-analytic study. Psychooncology. 2018 May 1 [cited 2024 Jan 13]; 27(5): 1426–1433. PubMed Abstract | Publisher Full Text\n\nAmamou B, Bannour AS, Yahia MBH, et al.: Haute prévalence du Burnout dans les unités Tunisiennes prenant en charge des patients en fin de vie. Pan Afr. Med. J. 2014 [cited 2024 Jan 13]; 19: 9. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAiken LH, Clarke SP, Sloane DM: Hospital staffing, organization, and quality of care: Cross-national findings. Nurs. Outlook. 2002 Sep 1 [cited 2024 Jan 13]; 50(5): 187–194. PubMed Abstract | Publisher Full Text Reference Source\n\nAl-Turki HA, Al-Turki RA, Al-Dardas HA, et al.: Burnout syndrome among multinational nurses working in Saudi Arabia. Ann. Afr. Med. 2010 [cited 2024 Jan 13]; 9(4): 226–229. PubMed Abstract | Publisher Full Text\n\nHamaideh SH: Burnout, social support, and job satisfaction among jordanian mental health nurses. Issues Ment. Health Nurs. 2011; 32(4): 234–242. PubMed Abstract | Publisher Full Text\n\nElbarazi I, Loney T, Yousef S, et al.: Prevalence of and factors associated with burnout among health care professionals in Arab countries: a systematic review. BMC Health Serv. Res. 2017 Jul 17 [cited 2024 Jan 13]; 17(1): 491. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPurvanova RK, Muros JP: Gender differences in burnout: A meta-analysis. J. Vocat. Behav. 2010 Oct 1; 77(2): 168–185. Publisher Full Text\n\nInnstrand ST, Langballe EM, Falkum E, et al.: Exploring within- and between-gender differences in burnout: 8 different occupational groups. Int. Arch. Occup. Environ. Health. 2011 Oct [cited 2024 Jan 13]; 84(7): 813–824. PubMed Abstract | Publisher Full Text\n\nKash KM, Holland JC, Breitbart W, et al.: Stress and burnout in oncology. Oncology (Williston Park). 2000 Nov 1 [cited 2024 Jan 13]; 14(11): 1621–33. discussion 1633. PubMed Abstract\n\nSobrequés J, Cebrià J, Segura J, et al.: Job satisfaction and burnout in general practitioners. Aten. Primaria. 2003 [cited 2024 Jan 13]; 31(4): 227–233. PubMed Abstract | Publisher Full Text | Free Full Text\n\nMaslach C, Goldberg J: Prevention of burnout: New perspectives. Appl. Prev. Psychol. 1998 Dec 1; 7(1): 63–74. Publisher Full Text\n\nUllrich A, FitzGerald P: Stress experienced by physicians and nurses in the cancer ward. Soc. Sci. Med. 1990 [cited 2024 Jan 13]; 31(9): 1013–1022. PubMed Abstract | Publisher Full Text\n\nJt B: Stress and stress management: an overview. J. Nurs. Educ. 1980.\n\nDe la Fuente-Solana EI, Gómez-Urquiza JL, Cañadas GR, et al.: Burnout and its relationship with personality factors in oncology nurses. Eur. J. Oncol. Nurs. 2017 Oct 1 [cited 2024 Jan 13]; 30: 91–96. Publisher Full Text Reference Source\n\nAlacacioglu A, Yavuzsen T, Dirioz M, et al.: Burnout in nurses and physicians working at an oncology department. Psychooncology. 2009 May 1 [cited 2024 Jan 13]; 18(5): 543–548. Publisher Full Text\n\nMaslach C, Jackson SE: The role of sex and family variables in burnout. Sex Roles. 1985 Apr [cited 2024 Jan 13]; 12(7–8): 837–851. Publisher Full Text\n\nQuattrin R, Zanini A, Nascig E, et al.: Level of Burnout Among Nurses Working in Oncology in an Italian Region.Number 4/July 2006. 2006 Jan 2 [cited 2024 Jan 13]; 33(4): 815–820. Reference Source\n\nCatt S, Fallowfield L, Jenkins V, et al.: The informational roles and psychological health of members of 10 oncology multidisciplinary teams in the UK. Br. J. Cancer. 2005 Nov 4 [cited 2024 Jan 13]; 93(10): 1092–1097. PubMed Abstract | Publisher Full Text | Free Full Text\n\nBressi C, Manenti S, Porcellana M, et al.: Haemato-oncology and burnout: an Italian survey. Br. J. Cancer. 2008 Mar 25 [cited 2024 Jan 13]; 98(6): 1046–1052. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSchraub S, Marx E: Le point sur le syndrome d’épuisement professionnel des soignants ou burn out, en cancérologie. Bull. Cancer. 2004 Sep 1 [cited 2024 Jan 13]; 91(9): 673–676. PubMed Abstract Reference Source\n\nSabbah I, Sabbah H, Sabbah S, et al.: Burnout among Lebanese nurses: Psychometric properties of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). Health N Hav. 2012; 04(09): 644–652. Publisher Full Text\n\nGulalp B, Karcioglu O, Sari A, et al.: Burnout: need help? J. Occup. Med. Toxicol. 2008 [cited 2024 Jan 13]; 3(1): 32. PubMed Abstract | Publisher Full Text | Free Full Text\n\nKoç Z, Masat S, Öztürk EA, et al.: Determination of level of job satisfaction and burnout of oncology nurses. Eur. J. Cancer. 2017 Feb; 72: S133. Publisher Full Text\n\nVahey DC, Aiken LH, Sloane DM, et al.: Nurse burnout and patient satisfaction. Med. Care. 2004 [cited 2024 Jan 13]; 42(2 Suppl): II57–66. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWallace JE, Lemaire JB, Ghali WA: Physician wellness: a missing quality indicator. Lancet. 2009 Nov 14 [cited 2024 Jan 13]; 374(9702): 1714–1721. Publisher Full Text Reference Source"
}
|
[
{
"id": "340752",
"date": "21 Nov 2024",
"name": "Margaret I Fitch",
"expertise": [
"Reviewer Expertise I have expertise in oncology nursing",
"psychosocial oncology and palliative care as well as extensive administrative and research 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\nThank you for the opportunity to review this manuscript. It is focused on an important topic of burnout in Nurses. As I read the manuscript, I noted several places where additional details would strengthen the article.\n1. In the abstract clarify that burnout has been well studied in some countries but not in the Arab Muslim contest. Also, the use of the phrase 'respond correctly' implies that there is a right or correct response. I am not convinced this is the best word to use here.\n\n2. In the initial introduction paragraph there ought to be a better link between relational care and burnout. It feels like there is some thought that needs to be added to connect the two notions.\n3. I believe it would be important when the descriptions about past research is added, that there is clarity whether the work was done in High Income Settings or other cultural contexts; then the case for why this burnout work is needed in an Arb Muslim context is needed. Is there an expectation there will be differences? Why? These ideas need to be part of the introduction and rationale for the research study.\n\n4. Explain why the 4 departments were selected.\n5. Explain how the questionnaires were distributed to the potential participants and how they were informed about consenting.\n6. When the discussion is added about comparable studies try to focus on recent work; the context of cancer care is changing and the recent picture is what we need to understand.\n7. In the discussion I think it would be important to be clear about where the repots are coming from - which ones are in other income settings and cultural settings. This would make the comparison more realistic. It is important to be clear about what is influencing the environment in your setting versus some of the other settings of past work.\n\n8. I would be helpful to have tables I and II in the text.\n\n9. please review the paper for typos and English grammar errors.\n10. Finally, please watch the use of single sentence paragraphs - it is better to try to summarize and present coherent thoughts within a fulsome paragraph.\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/13-1239
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https://f1000research.com/articles/13-500/v1
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17 May 24
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{
"type": "Research Article",
"title": "Concomitant Infection of Helicobacter pylori and Intestinal Parasites: Burden, Sociodemographic and Clinical Characteristics in Hospitalized Children and Adolescents in Northern Lebanon",
"authors": [
"Sara MINA",
"Sara Daher",
"Nour Mina",
"Ghalia Khoder",
"Sara Daher",
"Nour Mina"
],
"abstract": "Background\nHelicobacter pylori and intestinal parasites are well-known for their high prevalence in children, especially in developing countries. However, their concomitant infections are poorly documented. In this study, we aimed to evaluate the association between intestinal parasites and H. pylori among hospitalized children and adolescents with upper gastrointestinal complaints in Northern Lebanon.\n\nMethods A cross-sectional study was conducted involving 297 hospitalized pediatric patients, aged between 1 and 15 years, who presented with gastrointestinal symptoms. The socio-demographic, lifestyle, and gastrointestinal characteristics of all participants were analyzed. Fresh stool samples were collected and screened for the presence of intestinal parasites and H. pylori infections.\n\nResults 6.4% of the patients were positive for intestinal parasitic infections, 5.4% were positive for H. pylori infection, and 11.8% were co-infected. The results of the Chi-square test showed that H. pylori infection is significantly associated with parasitic infection but not with a particular species. The most frequent coinfection was H. pylori-Entamoeba histolytica (77.1%). Moreover, H. pylori infection was associated with overcrowding and infrequent washing of vegetables before eating. The prevalence of co-infections increased in patients of mothers with a primary educational level or less. In regards to clinical characteristics, our findings showed a statistically significant relationship between i) gastric reflux and H. pylori, and ii) severe diarrhea and parasitic infection.\n\nConclusion Our data highlighted the association between H. pylori and intestinal parasitic infections. Thus, H. pylori detection could be taken into consideration while screening for parasitic infections in children and adolescents.",
"keywords": [
"Co-infection",
"Lebanon",
"Intestinal parasites",
"Helicobacter pylori",
"Stool."
],
"content": "Introduction\n\nGastrointestinal symptoms are common in the pediatric population, especially in developing countries. Co-infections involving bacteria and protozoa are an emerging phenomenon featuring concurrent ecological niches or shared transmission routes and risk factors (Akoolo et al., 2022). Consequently, co-infecting pathogens may interplay synergistically or antagonistically and modulate disease severity and host health outcomes (Hoarau et al., 2020; Devi et al., 2021). Intestinal parasites and the pathobiont bacterium Helicobacter pylori (H. pylori) are well known for their high prevalence in children, especially in low-resource settings.\n\nH. pylori infection has been extensively investigated over the last 30 years. It may currently be the most well-studied chronic bacterial infection in humans in a specific biological niche, specifically in the gut territory, and one of the major public health problems (Hooi et al., 2017). H. pylori colonization is one of the most prevalent infectious diseases and is predominantly acquired during childhood. A higher burden was reported in developing countries at a younger age than in developed countries (Borka Balas et al., 2022). Despite the vast number of studies that have been conducted to extensively investigate the spread of H. pylori, its main route of transmission is still elusive and no predominant mode has been yet identified. It is widely believed that person-to-person transmission is the most common mode of transmission. Moreover, it has been proven that H. pylori can be transmitted vertically or horizontally by three possible pathways: the fecal-oral, the oral-oral, and the gastro-oral routes (Kayali et al., 2018). Of note, recently published data pointed out the probable role of untreated water and food products in the environmental transmission of H. pylori (Vesga et al., 2023). However, the scarcity of data failed to ascribe a definite foodborne transmission, thus extensive epidemiological studies should be performed to corroborate this hypothesis. Clinical manifestations are non-specific but some may be alarming in children such as persistent abdominal pain, vomiting, and gastrointestinal bleeding that require histopathologic examination of H. pylori (Aguilera Matos et al., 2020). Gastric reflux is often associated with H. pylori infection even without the presence of macroscopic lesions on gastroduodenal mucosa (Burkitt et al., 2017).\n\nIntestinal parasites are significant contributors to morbidity and mortality in the pediatric population. Their prevalence is significantly associated with poor sanitation and fecal contamination of water supplies (Hernández-Castro et al., 2024). Major burdens of intestinal parasitic infections in children are attributed to members of the Entamoeba complex (Entamoeba histolytica (E. histolytica), Entamoeba dispar and Entamoeba moshkovskii), Blastocystis hominis (B. hominis), Giardia lamblia (G. lamblia) (syn. Giardia intestinalis and Giardia duodenalis), and Cryptosporidium. Their transmission typically occurs through the fecal-oral route after direct or indirect contact (by contaminated food or water) with the infective forms (cysts/oocysts) (Ahmed, 2023). In Lebanon, recent studies reported cases of E. histolytica infection in South Lebanon and Beirut (Salami et al., 2019; El Achkar et al., 2023). Other protozoa including B. hominis, Entamoeba coli (E. coli), and G. lamblia were also found but at lower prevalence (El Achkar et al., 2023).\n\nSeveral previous studies from different locations have highlighted a potential association between intestinal parasites and H. pylori (Ankarklev et al., 2012; Seid et al., 2018; Ibrahim et al., 2019). Since these pathogens are likely to share similar routes of transmission and risk factors, it is crucial to investigate this type of co-infection in the pediatric population. Not much data is available in Lebanon about the prevalence of H. pylori in this population and its potential association with intestinal parasitic infections. Understanding the prevalence pattern of H. pylori and intestinal parasite co-infections in the Lebanese pediatric population and their risk factors will aid in prioritizing public health efforts to better manage the burden of these infections and long-term complications.\n\n\nMethods\n\nThe sample size was calculated using the sample size calculator (https://select-statistics.co.uk/calculators/sample-size-calculator-population-proportion/) with a confidence level of 95%, a margin of error of 5%, and an estimated prevalence of 25% based on a previous local study (Khoder et al., 2021). The suggested sample size was initially 289 participants; however, 297 participants were included to account for any equivocal data that may be removed during the study. Patients eligible for the study consisted of any hospitalized child or adolescent presenting with complaints of one or more upper gastrointestinal symptoms at one of the two healthcare facilities during the study period. Pediatric patients met the following inclusion criteria: (i) aged less than 15 years old, (ii) onset of symptoms within the last week. An informed consent statement was signed by the patient or his parents. Participants were excluded if they i) had chronic diarrhea, ii) had a documented history of non-infectious etiology (symptoms persisting for longer than 4 weeks), iii) had recent antiparasitic therapy or proton pump inhibitors and bismuth preparations within the last two weeks before study enrollment, and iv) had viral diarrhea. Each patient or legal representative completed a face-to-face questionnaire addressing sociodemographic and socioeconomic characteristics, lifestyle, and clinical characteristics (presence of gastrointestinal symptoms).\n\nA stool specimen was collected from each patient before any prescribed antimicrobial therapy. Fresh stool samples were labeled and received in an airtight transport container and divided into two parts. One to two milligrams were immediately examined macroscopically for color and consistency. In addition, the presence of whole or partial parts of parasites was investigated using wet mount preparation in normal saline by direct-light microscopy (DLM). All examinations were repeated twice by two experienced microbiologists. The remaining stool samples were stored either at 4°C for up to three days or immediately frozen at −20°C until tested for the presence of H. pylori antigen. H. pylori infection was detected from patients’ fecal specimens by the H. PYLORI QUICK CHEKTM kit (TECHLAB, USA), a rapid qualitative sandwich enzyme immunoassay that uses immobilized capture monoclonal anti-H. pylori antibodies. Diluted fecal samples and controls were added to each antibody-coated microtiter well. Tests were performed in duplicate according to the manufacturer’s instructions. Absorbance equal to or above 0.12 at 450 nm or 0.08 at 450/620 nm or 450/630 nm was considered a positive result.\n\nData were entered and statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS) program (version 21.0) (https://www.ibm.com/products/spss-statistics). Descriptive statistics were reported as frequencies and percentages for the categorical variables and as means and standard deviations (SD) for the continuous variables. The differences in gastrointestinal symptoms, sociodemographic characteristics, and hygiene-related practices between study groups were examined using the Chi-square test for categorical variables and independent t-tests for continuous variables. A p ≤ 0.05 was considered statistically significant.\n\n\nResults\n\nThe sociodemographic characteristics of 297 children and adolescents included in this study are presented in Table 1. Patients aged less than 5 years constituted 68.0% of the study sample, followed by 23.9% aged 5-10 years, and 8.1% aged 10-15 years. Most of the patients were residing in urban areas (79.8%). In addition, 61.5% and 80.5% of mothers and fathers respectively, had an educational level of primary school or less. Furthermore, 83.5% of the study sample households reported having an insufficient monthly income.\n\nPatients were divided into four groups according to their infection status: i) intestinal parasitic infection only (IP infection), ii) H. pylori infection only (HP infection), iii) H. pylori and intestinal parasitic co-infection (HP-IP co-infection), and iv) H. pylori and intestinal parasites free infections (Free Infection).\n\nAmong the 297 tested patients’ stools, 6.4% were positive for IP infection, 5.4% were positive for HP infection, 11.8% were positive for HP-IP co-infection, and 76.4% were negative (free infection). Furthermore, E. histolytica accounted for the highest proportion of parasitic infection (77.8%), followed by G. lambliae (20.4%), and E. coli (1.9%). However, no statistical significance between the type of parasite and HP-IP co-infection was observed (Table 2). Furthermore, when diagnosed with HP infection, a higher percentage of patients exhibited a positive mixed parasitic infection compared to cases where H. pylori infection was absent (66.0% vs. 35.2%, p < 0.001) (Table 2).\n\n* Cells have expected count less than 5 – used Fisher’s test instead of Pearson Chi-Square.\n\nThe most frequently reported symptoms among children and adolescents were vomiting (56.6%), abdominal pain (39.4%), mild diarrhea (33.3%), and fever (28.3%) with no statistically significant differences between study groups (p > 0.005) as observed in Table 3 and Figure 1. On the other hand, children infected with H. pylori only or co-infected reported higher frequencies of reflux symptom (37.5% and 17.1% respectively) than those with intestinal parasitic infection only (5.3%) or without infection (6.6%) (p = 0.001). However, patients infected with H. pylori alone or free of both infections had zero or lower percentages of severe diarrhea (0.0% and 15.9% respectively) compared to those infected with intestinal parasitic infections (36.8%) or both H. pylori and intestinal parasitic infections (25.7%) with a statistically significant difference between the study infectious groups (p = 0.013).\n\n* Cells have expected count less than 5 – used Fisher’s test instead of Pearson Chi-Square.\n\nTable 4 summarizes the associations between the four study groups and the sociodemographic and hygiene-related practices. Children and adolescents residing in urban areas exhibited a higher susceptibility to both mono-infections and mixed infections by intestinal parasites and H. pylori in comparison to their rural counterparts (p = 0.453). Additionally, a significantly elevated crowding index was observed among patients with HP infection when compared to other groups (p = 0.025).\n\n* Cells have expected count less than 5 – used Fisher’s test instead of Pearson Chi-Square.\n\nChildren and adolescents of mothers with primary education or lower exhibited a significantly elevated likelihood of HP-IP compared to those born to mothers with secondary education or higher (p = 0.025). Furthermore, patients from households that reported never washing vegetables before eating were significantly more likely to be infected with H. pylori only (p = 0.010). Surprisingly, children and adolescents from households that reported washing hands correctly after defecating were significantly more likely infected with intestinal parasites only (p = 0.046).\n\n\nDiscussion\n\nGastrointestinal complaints including gastric reflux, diarrhea, and vomiting are one of the major indications for pediatric hospital admissions (Dipasquale et al. 2018). H. pylori, E. histolytica, and G. lamblia are the most common intestinal pathogens in humans residing in low- and middle-income countries. In the present study, the overall prevalence of intestinal parasitic infection was found to be 54%, among them E. histolytica was the predominant protozoan parasite (77.8%). It is worth noting that our findings indicate that the North Lebanese pediatric population were at higher risk of intestinal parasitic infections than their counterparts admitted to a private tertiary care hospital located in South Lebanon (26.3%) (Ghssein et al., 2018). In addition, a recent retrospective study addressed the prevalence of intestinal parasites in all age groups of patients at a tertiary care center in Beirut where E. histolytica accounted for 7% and 10% of the cases during the pre-COVID and post-COVID periods, respectively (El Achkar et al., 2023). Although these three governorates belong to the same biogeographic region and share similar geographical and climatic conditions, the observed discrepancies could be explained by intrinsic differences in sanitation infrastructures and facilities. Moreover, this difference can be also associated with compounded crises following the deteriorated economic condition, and most importantly the Syrian influx that is greatly pronounced in the Northern region of Lebanon.\n\nOur findings showed an increase in the prevalence of H. pylori infection with overcrowding and infrequent washing of vegetables before eating. These factors may facilitate the transmission of H. pylori within households and support the intra-familial clustering of this pathogen (Palanduz et al., 2018). These findings were consistent with recent reports from different countries where living in crowded households was found to be a significant risk factor for H. pylori infection (Aitila et al., 2019; Che et al., 2022). Moreover, our findings support and extend evidence reported in several studies worldwide regarding the transmission of H. pylori through unwashed vegetables (Szaflarska-Popławska and Soroczyńska-Wrzyszcz, 2019; Yisak et al., 2022). This can be explained by the direct contamination of vegetables by the bacterium or by irrigation with untreated wastewater (Kayali et al., 2018). In addition, vegetables may provide a suitable niche for H. pylori survival thanks to the ability of this bacteria to form biofilm and microcolonies on vegetable surfaces for an extended period (Ng et al., 2017). Thus, vegetables may potentially serve as a transmission vehicle for H. pylori, however, this hypothesis is still poorly documented.\n\nIntestinal parasites and H. pylori share similar predisposing factors, thus a better understanding of the epidemiology of H. pylori infection in children infected with intestinal parasites is crucial to investigate whether H. pylori provides a favorable niche for intestinal parasitic infections or vice versa. We did not find any statistical significance between HP and a specific IP infection, so our analysis was based on HP-IP co-infections. Our findings showed that higher H. pylori colonization was found among individuals infected with intestinal parasites than non-infected subjects. The most frequent intestinal parasites were protozoa, and specifically, the association of H. pylori with E. histolytica was the most prevalent. Comparative data highlighting these co-infections were reported in African countries. A similar E. histolytica and H. pylori co-infection (12%) was reported in a Sudanese study that included individuals from all age groups (Yousif Abd Elbagi et al., 2019). Another cross-sectional study enrolled children aged 14 years or younger living in Ethiopia and showed a 23% prevalence of coinfection with any intestinal parasite and H. pylori. Maternal education was described as a significant risk factor for co-infection (Spotts et al., 2020). Abd El Hameed et al. (2021) showed an association between H. pylori and parasitic infections, especially G. lamblia (35.9%), in Egyptian children aged between 1 and 15 years. In Europe, a single study conducted in Northeastern Italy found a significant association between H. pylori and concomitant parasitic infection in different ethnicities, with Blastocystis being the most frequent co-infecting parasite (Pomari et al., 2020). Fuenmayor-Boscán et al. (2016) reported a significant association with helminths in South American children aged less than 5 years old. Nonetheless, their finding disagreed with ours that showed an inverse association between H. pylori and G. lamblia, indicating an antagonistic interaction that may hinder the colonization of the gut by exogenous intestinal pathogens. These associations detected in different countries support the similar fecal-oral route in the transmission of the etiologic agents. However, the environmental exposure factors to the fecal-oral transmission route investigated herein were associated with H. pylori only regarding the infrequency of washing vegetables before eating (p = 0.01) and handwashing with soap after defecating (p = 0.046). Regarding the epidemiological factors associated with co-infections, children and adolescents of mothers with primary education or less were significantly more likely to be co-infected compared with children from mothers with higher educational levels (p = 0.025). It is noteworthy that the homogenous lifestyle of this study population may have masked any possible association between this environmental factor and intestinal infections or co-infections. Moreover, urease production by H. pylori converts urea into carbon dioxide and ammonia resulting in buffering the environment and thus enhancing bacterial colonization. Changes in the local environment could result in a higher incidence of intestinal parasitic infections by modulating the host’s immune responses. Furthermore, H. pylori was described as a candidate training of immune cells, especially primary human monocytes, towards subsequent microbial pathogens (Frauenlob et al., 2023).\n\nVomiting was the most frequent complaint (60%) in co-infected children, and in patients infected with intestinal parasites (73.7%), while it was less frequently recorded in H. pylori-infected and in co-infected individuals (43.8% and 60%, respectively). In addition, gastric reflux was significantly associated (37.5%; p = 0.001) with H. pylori infection. On the other hand, severe diarrhea was less recorded in co-infected children (24.7%) than in those with intestinal parasitic infection (36.8%; p = 0.013). Consequently, co-infection could modulate the host immune response and, thus, the clinical manifestation of each pathogen regarding severe diarrhea. Indeed, it has been described that children who tested positive for H. pylori are at lower risk of diarrheal diseases, especially during giardiasis, than children who are negative for this infection (Abd El Hameed et al., 2021). These results suggest that pediatric infections with H. pylori may condition a balanced host immune response to subsequent infections by playing a potential protective role during the diarrheal episode in co-infected patients and suppressing hyperimmune responses in the gut. Previous investigations seem to support this argument. Interferon-gamma (IFN-γ) is secreted along with Th1 responses toward intestinal amebiasis and was shown to play a protective role by clearing the amebae (Deloer et al., 2017). It can be also expressed at a higher level in H. pylori-positive children than in healthy children (Yu et al., 2020). Thus, patients enrolled in our study can be at the early stage of amebiasis and IFN-γ may reduce the risk of severe outcomes in H. pylori-positive individuals. However, our findings are not consistent with previous reports that demonstrated that the presence of intestinal protozoa in the gut together with H. pylori amplifies the recruitment of Th1 cells. This leads to exaggerated inflammation and tissue damage and thus it may worsen the disease (Krzyżek and Gościniak, 2017).\n\nThe present study is the first to report novel assessment and risk data on the association between H. pylori and intestinal parasites in the Lebanese pediatric population attending tertiary care hospitals. Future large-scale and multicenter epidemiological studies should be performed using different diagnostic methods to support these findings and to explore the mechanistic interaction between H. pylori and particular types of parasitic infection. Understanding these interactions highlights the importance of considering and mitigating these co-infections by health authorities and decision-makers to improve the methods of detection and implement effective intervention measures and public health strategies.\n\n\nConclusion\n\nThe association between H. pylori and intestinal parasitic infections was assessed for the first time among Lebanese hospitalized children and adolescents. A moderate prevalence of H. pylori and intestinal parasite co-infection was observed and associated with the low educational level of the participants’ mothers. In regards to the clinical manifestations reported in this study, gastric reflux was significantly associated with H. pylori infection and severe diarrhea showed a significant relationship with intestinal parasitic infection. This study could provide valuable insights into the complexity of the interconnected relationship between enteric pathogens and how they can promote each other’s persistence in the gut, and thus affect child health and development.\n\nThis cross-sectional hospital-based study was conducted in two hospitals located in Northern Lebanon from October 2023 to December 2023. The institutional review board (IRB) committee at Beirut Arab University approved this study on October 2023 (2023-H-0154-HS-R-0548), in accordance with the Declaration of Helsinki. Written informed consent was obtainedfrom parents or legal guardians before participation in the study.",
"appendix": "Data availability\n\nFigshare: Raw data collected from patients enrolled in this study: Mina, Sara (2024). RAW Data_Children_HP and Parasites.sav. figshare. Dataset. https://doi.org/10.6084/m9.figshare.25292653.v1.\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nFigshare: Questionnaire Concomitant infection of Helicobacter pylori and intestinal parasites, https://doi.org/10.6084/m9.figshare.25690047.v1\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nAbd El Hameed YF, Boghdadi AM, Ghobrial CM, et al.: Association of Helicobacter pylori and parasitic infections in childhood: impact on clinical manifestations and implications. J. Parasit. Dis. 2021 Sep; 45(3): 790–796. Epub 2021 Feb 23. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAguilera Matos I, Diaz Oliva SE, Escobedo AA, et al.: Helicobacter pylori infection in children. BMJ Paediatr. Open. 2020 Aug 3; 4(1): e000679. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAhmed M: Intestinal Parasitic Infections in 2023. Gastroenterology Res. 2023 Jun; 16(3): 127–140. Epub 2023 Jun 11. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAitila P, Mutyaba M, Okeny S, et al.: Prevalence and Risk Factors of Helicobacter pylori Infection among Children Aged 1 to 15 Years at Holy Innocents Children’s Hospital, Mbarara, South Western Uganda. J. Trop. Med. 2019 Mar 7; 2019: 9303072. PubMed Abstract | Publisher Full Text | Free Full Text\n\nAkoolo L, Rocha SC, Parveen N: Protozoan co-infections and parasite influence on the efficacy of vaccines against bacterial and viral pathogens. Front. Microbiol. 2022 Nov 25; 13: 1020029. 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PubMed Abstract | Publisher Full Text\n\nNg CG, Loke MF, Goh KL, et al.: Biofilm formation enhances Helicobacter pylori survivability in vegetables. Food Microbiol. 2017 Apr; 62: 68–76. Epub 2016 Oct 3. PubMed Abstract | Publisher Full Text\n\nPalanduz A, Erdem L, Cetin BD, et al.: Helicobacter pylori infection in family members of patients with gastroduodenal symptoms. A cross-sectional analytical study. Sao Paulo Med. J. 2018 May-Jun; 136(3): 222–227. Epub 2018 Jun 4. PubMed Abstract | Publisher Full Text | Free Full Text\n\nPomari E, Ursini T, Silva R, et al.: Concomitant Infection of Helicobacter pylori and Intestinal Parasites in Adults Attending a Referral Centre for Parasitic Infections in North Eastern Italy. J. Clin. Med. 2020 Jul 24; 9(8): 2366. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSalami A, Fakih H, Chakkour M, et al.: Prevalence, risk factors and seasonal variations of different Enteropathogens in Lebanese hospitalized children with acute gastroenteritis. BMC Pediatr. 2019 Apr 30; 19(1): 137. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSeid A, Tamir Z, Kasanew B, et al.: Co-infection of intestinal parasites and Helicobacter pylori among upper gastrointestinal symptomatic adult patients attending Mekanesalem Hospital, northeast Ethiopia. BMC. Res. Notes. 2018 Feb 20; 11(1): 144. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSpotts H, Walelign S, Tesfaye M, et al.: Concurrent infection of intestinal parasites and Helicobacter pylori among school-age children in Central Ethiopia. Parasite Epidemiol. Control. 2020 Aug 25; 11: e00177. PubMed Abstract | Publisher Full Text | Free Full Text\n\nSzaflarska-Popławska A, Soroczyńska-Wrzyszcz A: Prevalence of Helicobacter pylori infection among junior high school students in Grudziadz, Poland. Helicobacter. 2019 Feb; 24(1): e12552. Epub 2018 Nov 15. Erratum in: Helicobacter. 2019 Dec; 24(6): e12673. PubMed Abstract | Publisher Full Text\n\nVesga FJ, Beltrán-Benavides AR, Márquez-Duque AM, et al.: Helicobacter pylori virulence genotypes in Bogotá River and wastewater treatment plants in Colombia. Helicobacter. 2023 Dec; 28(6): e13023. Epub 2023 Sep 27. PubMed Abstract | Publisher Full Text\n\nYisak H, Belete D, Mahtsentu Y: Helicobacter pylori infection and related factors among pregnant women at Debre Tabor General Hospital, Northwest Ethiopia, 2021: Anemia highly related with H. pylori. Womens Health (Lond). 2022 Jan-Dec; 18: 17455057221092266. 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}
|
[
{
"id": "284870",
"date": "13 Jun 2024",
"name": "Marwa Gouda",
"expertise": [
"Reviewer Expertise parasitology",
"infectious 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\nThank you for the opportunity to review the manuscript titled “Concomitant Infection of Helicobacter pylori and Intestinal Parasites: Burden, Sociodemographic and Clinical Characteristics in Hospitalized Children and Adolescents in Northern Lebanon”. I would like to appreciate the authors' effort to undertake this valuable task. I have some concerns that may help to improve the manuscript.\nThe authors reported limited research in their subject matter, however by searching some authors previously documented this subject with the same details. It would be better to concise limited research to the locality of research and add data concerning the prevalence of the examined pathogen in the research locality. It would be beneficial to have a more detailed background on why the concomitant infection of H. pylori and intestinal parasites specifically is of interest. The procedures used in stool examinations are limited and inadequate to diagnose all intestinal parasites. Have the authors performed any other techniques or special stains in diagnosis?? Consider whether there should be more detail on the specific laboratory techniques used for detecting H. pylori and intestinal parasites. It might be useful for the authors to hypothesize why certain sociodemographic factors (e.g., mother's education level) are associated with higher rates of co-infection. The study's limitations are not explicitly mentioned in the provided snippet. Please, discuss potential limitations and their impact on the findings. The authors should provide suggestions for future research based on their 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? 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": "12609",
"date": "15 Oct 2024",
"name": "Sara MINA",
"role": "Author Response",
"response": "Dear Dr. Gouda, We sincerely appreciate your efforts in refining our manuscript. Your insightful comments were highly valuable and helped us to significantly improve the quality of our work. Every comment and concern raised has been meticulously addressed, and we have made all the necessary modifications. These changes have been comprehensively tracked in review mode for your reference. We are hopeful that with these revisions, the manuscript now fulfills the requirements for publication in the F1000Research journal. Comment #1: The authors reported limited research in their subject matter, however by searching some authors previously documented this subject with the same details. It would be better to concise limited research to the locality of research and add data concerning the prevalence of the examined pathogen in the research locality. Response: Thank you for your valuable comments and suggestions. We have now included additional references related to the prevalence of the pathogen in the research locality, as recommended (Naous et al., 2007; Al Kirdy et al., 2020). You may view the revisions made in the track changes mode. The Naous et al. (2007) study was initially omitted from the manuscript because it is an older fecoprevalence study that focused solely on the prevalence of H. pylori in children, without addressing any concurrent intestinal parasites. However, we have reconsidered its relevance and included it as per your suggestion. Comment #2: It would be beneficial to have a more detailed background on why the concomitant infection of H. pylori and intestinal parasites specifically is of interest. Response: We appreciate the valuable feedback provided by the reviewer. Indeed, the authors have not highlighted enough the interest behind the concomitant infection of H. pylori and intestinal parasites. Co-infections can modulate disease dynamics through synergistic or antagonistic interactions. Interestingly, the co-existence of H. pylori and intestinal parasites may alter the disease severity and skew host immune responses (Jaka and Smith, 2024; Krzyżek and Gościniak, 2017). Changes have been implemented and tracked under review mode. Comment #3: The procedures used in stool examinations are limited and inadequate to diagnose all intestinal parasites. Have the authors performed any other techniques or special stains in diagnosis?? Response: Thank you for your valuable comments. The authors acknowledge the importance of utilizing the most appropriate techniques for diagnosing intestinal parasites. However, given the available resources in our research laboratory and the project’s budget constraints, we primarily relied on wet mount preparations in normal saline and direct-light microscopy (DLM) for detecting intestinal parasites, observing either partial or whole parasite structures. To ensure accuracy, all examinations were conducted in duplicate by two experienced microbiologists. Additionally, a modified Ziehl-Neelsen (MZN) staining technique at 1,000× magnification was employed to detect coccidian parasites. For the detection of H. pylori in stool samples, we utilized the H. PYLORI QUICK CHEK™ kit (TECHLAB, USA), following established methodologies (Halland et al., 2021). Halland M, Haque R, Langhorst J, Boone JH, Petri WA. Clinical performance of the H. PYLORI QUIK CHEK™ and H. PYLORI CHEK™ assays, novel stool antigen tests for diagnosis of Helicobacter pylori. Eur J Clin Microbiol Infect Dis. 2021 May;40(5):1023-1028. doi: 10.1007/s10096-020-04137-7. Epub 2021 Jan 3. PMID: 33389260; PMCID: PMC7778841. Comment #4: Consider whether there should be more detail on the specific laboratory techniques used for detecting H. pylori and intestinal parasites. Response: Thank you for your suggestion. It was addressed in the previous response to comment #3. Comment #5: It might be useful for the authors to hypothesize why certain sociodemographic factors (e.g., mother's education level) are associated with higher rates of co-infection. Response: Thank you for your insightful comment. We agree that the relationship between a mother’s education level and higher rates of co-infection was not sufficiently explored in our initial discussion. We hypothesize that a mother’s education level can significantly influence hygiene practices within the household, which may impact the incidence of microbial infections in children. This hypothesis is supported by findings from Wangda et al. (2017), which demonstrated that a mother’s educational background is closely linked to her knowledge and traditional practices regarding the prevention and treatment of diseases in children (Wangda et al., 2017). Comment #6: The study's limitations are not explicitly mentioned in the provided snippet. Please, discuss potential limitations and their impact on the findings. Response: Thank you for highlighting this point. To the best of our knowledge, the present study is the first to report novel assessment and risk data on the association between H. pylori and intestinal parasites in a Lebanese pediatric population attending tertiary care hospitals. However, the findings may not be generalizable to the Lebanese population. The cross-sectional design did not allow for drawing causal conclusions. In addition, the recruitment of hospitalized patients with gastrointestinal symptoms may affect internal validity. Adding to this, the authors agree that using more appropriate techniques to identify intestinal parasites with more precision could be one of the limitations to be considered in future studies. Comment #7: The authors should provide suggestions for future research based on their findings. Response: Thank you for your suggestion. In this study, we focused on hospitalized children and adolescents in Northern Lebanon. Moving forward, we plan to expand this research to include asymptomatic children and adults, given that H. pylori infection is often asymptomatic and widespread. To build on our findings, future large-scale, multicenter epidemiological studies with appropriate control groups are needed. These studies should employ a variety of diagnostic methods to further validate our results and investigate the mechanistic interactions between H. pylori and specific parasitic infections. Additionally, metagenomic analyses of stool samples could help identify distinct pathogenic profiles (including parasites, viruses, and fungi) and their associations with H. pylori virulence factors, such as CagA, VacA, babA, and others."
}
]
},
{
"id": "318918",
"date": "19 Sep 2024",
"name": "Steven F Moss",
"expertise": [
"Reviewer Expertise Helicobacter pylori",
"susceptibility testing",
"NGS"
],
"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 study by Mina et. al the prevalence and associations between intestinal parasitic infection and H. pylori infection is examined among a cohort of children aged 1-15 years hospitalized with gastrointestinal symptoms in Northern Lebanon. A modest association between H. pylori infection and intestinal parasites is demonstrated, suggesting similar modes of transmission. Some other positive clinical correlations are reported, suggesting etiological factors. I have the following concerns:\n\nThe study involved parasite testing, interviews with patients/and or their family members etc beyond that necessary for routine investigation of the mainly upper and non-specific GI symptoms. Was IRB approval obtained for these extra elements? How were the extra tests and interviews funded?\n\nDetails regarding how the histories of vegetable washing, handwashing practices etc are obtained is lacking. Were the patients quizzed, or were there relatives? What questions were asked specifically?\n\nWithin the methods section the authors describe that they collected fresh stool samples for H. pylori and parasite evaluation. However, some of the patients had diarrhea which could dilute the samples, leading to false negative results. This may explain why the H. pylori prevalence in this cohort is lower than found in many other studies from the middle East. There are no controls, e.g patients without gastrointestinal symptoms, that could shed light upon this issue.\n\nThe protocol for pathogen testing is not well-defined. Which bacterial and protozoal species were evaluated specifically. Were stools cultured for salmonella, shigella, etc? How were viral infections excluded?\n\nThe authors should discuss the clinical implications of their findings\n\nAs a cross sectional study there are intrinsic limitations including lack of ability to determine causality that should be outlined within the manuscript. Generalizability is also a concerns, as well as the methodological issues discussed above. I suggest the authors include the strengths and limitations of their study design within the discussion or conclusion section\n\nOverall, I would recommend against acceptance until the above recommendations and comments are 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? Partly\n\nAre sufficient details of methods and analysis provided to allow replication by others? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "12610",
"date": "15 Oct 2024",
"name": "Sara MINA",
"role": "Author Response",
"response": "Dear Dr. Moss, We sincerely appreciate your efforts in refining our manuscript. Your insightful comments were highly valuable and helped us significantly improve the quality of our work. Every comment and concern raised has been meticulously addressed, and we have made all the necessary modifications. These changes have been comprehensively tracked in review mode for your reference. We are hopeful that with these revisions, the manuscript now fulfills the requirements for publication in the F1000Research journal. Comment #1: The study involved parasite testing, interviews with patients/and or their family members etc beyond that necessary for routine investigation of the mainly upper and non-specific GI symptoms. Was IRB approval obtained for these extra elements? How were the extra tests and interviews funded? Response: IRB approval for the entire study, including additional tests and interviews, was obtained from the Institutional Review Board (IRB) at Beirut Arab University (Approval No. 2023-H-0154-HS-R-0548). Furthermore, parental consent and child assent were secured before participation. All participants provided informed consent, confirming their voluntary involvement in the study. There was no incentive for the interviews, and the extra tests were performed as a part of the routine hospital investigations. Comment #2: Details regarding how the histories of vegetable washing, handwashing practices etc are obtained is lacking. Were the patients quizzed, or were there relatives? What questions were asked specifically? Response: Thank you for these critical questions. The patients were interviewed in the presence of their parents. Adolescents responded by themselves, and the parents responded on behalf of younger participants. To assess the level of handwashing practices, the participants or their parents were asked about using water only or water and soap, the duration of handwashing, and how often they wash their hands after toilet. In addition, they were asked about washing vegetables under running water and rubbing them with their hands to remove surface microorganisms. Comment #3: Within the methods section the authors describe that they collected fresh stool samples for H. pylori and parasite evaluation. However, some of the patients had diarrhea which could dilute the samples, leading to false negative results. This may explain why the H. pylori prevalence in this cohort is lower than found in many other studies from the middle East. There are no controls, e.g patients without gastrointestinal symptoms, that could shed light upon this issue. Response: Thank you for this valuable and insightful comment. The authors fully agree that watery stool samples could lead to a higher incidence of false negatives. According to the manufacturer's guidelines for the H. PYLORI QUICK CHEK™ kit (TECHLAB, USA), watery stools were not collected for the stool antigen test (SAT). To address this, patients with severe diarrhea were asked to provide stool samples immediately after the episode had subsided. The authors acknowledge that this may present a limitation in the study. We concur that future research should focus on asymptomatic subjects to explore similar correlations between H. pylori and intestinal parasites. Comment #4: The protocol for pathogen testing is not well-defined. Which bacterial and protozoal species were evaluated specifically. Were stools cultured for salmonella, shigella, etc? How were viral infections excluded? Response: Thank you for this important technical question. In this study, stool samples were not cultured for the isolation of Salmonella or Shigella. The primary focus of the study was on detecting H. pylori using the H. PYLORI QUICK CHEK™ kit, as well as identifying intestinal parasites through direct-light microscopy (DLM). Additionally, a modified Ziehl-Neelsen (MZN) staining technique at 1,000× magnification was used to detect coccidian parasites. Patients with culture-confirmed bacterial gastroenteritis or diagnosed viral infections, such as rotavirus or adenovirus, identified through routine hospital investigations, were excluded from the study. Comment #5: The authors should discuss the clinical implications of their findings Response: Thank you for this valuable comment. H. pylori is a known contributor to gastric ulcers, chronic gastritis, and potentially gastric cancer. However, when parasitic infections occur simultaneously, they can intensify or obscure these symptoms, making diagnosis more challenging. Clinicians may need to adopt a broader differential diagnosis when evaluating gastrointestinal issues, ensuring both bacterial and parasitic infections are considered. Moreover, the interaction between H. pylori and parasitic infections may impact treatment options. For instance, standard H. pylori therapies like antibiotics might be less effective if parasitic infections are not treated concurrently. Administering antiparasitic therapies alongside H. pylori eradication could improve outcomes but may also introduce concerns about drug interactions or resistance. These findings may shape screening protocols, emphasize the importance of integrated treatment strategies, and prompt the development of guidelines for managing co-infections in clinical practice. Comment #6: As a cross sectional study there are intrinsic limitations including lack of ability to determine causality that should be outlined within the manuscript. Generalizability is also a concerns, as well as the methodological issues discussed above. I suggest the authors include the strengths and limitations of their study design within the discussion or conclusion section Response: Thank you for this valuable feedback. To the best of our knowledge, this study is the first to provide novel data on the association between H. pylori and intestinal parasites in a Lebanese pediatric population attending tertiary care hospitals. This represents a key strength of the study, especially given the limited epidemiological research on H. pylori in Lebanon. However, we acknowledge that the findings may not be fully generalizable to the broader Lebanese population. The cross-sectional design of the study limits the ability to establish strong causal relationships, and the recruitment of hospitalized patients with gastrointestinal symptoms may have affected internal validity. These limitations have been discussed in the discussion section, as suggested, and are reflected in the track changes."
}
]
}
] | 1
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https://f1000research.com/articles/13-500
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https://f1000research.com/articles/13-1235/v1
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15 Oct 24
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{
"type": "Case Study",
"title": "GIS integration for spatial analysis of urban expansion in Tisaleo canton (Ecuador).",
"authors": [
"Patricia Alexandra Chiriboga Zamora",
"Ligia Ximena Tapia Hermida",
"Martha Lucia Romero Flores",
"Danny Francisco Espín Real",
"Pedro A. Carretero Poblete",
"Ligia Ximena Tapia Hermida",
"Martha Lucia Romero Flores",
"Danny Francisco Espín Real"
],
"abstract": "Political or economic interests have led to an empirical zonal delimitation, and the deficient use of Geographic Information Systems does not allow the specific characterisation of the territories. This article aims to determine the spatial analysis of the urban expansion areas of the canton of Tisaleo by integrating Geographic Information Systems, using a quantitative research method. The main components analysed are: the situational diagnosis of the canton through the characterisation of its biophysical component, its human settlements and the public system of facilities and social services that support it. Based on this information, an interrelation of the data collected is carried out to complement a spatial analysis with GIS software (ArcGis/QGis, ESRI, 2018). The results show that in the canton of Tisaleo there are areas suitable for urban growth, but their limits are overdimensioned, i.e. they include areas that do not have the aptitude to be urbanised, as well as rural areas that have the characteristics to be considered urban.",
"keywords": [
"urban expansion",
"geographic information systems",
"spatial analysis",
"Tisaleo."
],
"content": "Introduction\n\nThe present proposal was developed based on the results obtained from the surveys carried out on the independent variable “Spatial Analysis” and the dependent variable “Expansion of the urban area”; on the properties of the canton of Tisaleo; the same data that allowed us to know the ordered urban growth, this allows us to carry out spatial analysis studies integrating geographic information systems to identify the urban expansion which integrates the territorial components: biophysical, socio-cultural, economic, human settlements, mobility, energy, connectivity and political institutions. Software belonging to the Geographic Information Systems (GIS) are tools that have been generated since the 1970s that improve the collection, processing, analysis and management of geographically referenced data, linking their alphanumeric (quantitative data) and geographic attributes. In GIS, data are generally distributed in layers that represent each characteristic, type of data or event that takes place in a specific geographic space.\n\nTisaleo is one of the nine cantons of the province of Tungurahua, located in the southwest of the province. It has an area of 59.64 square kilometres, which represents 1.75% of the province’s territory. It is bordered to the north and west by Ambato, to the south by the canton of Mocha and to the east by the canton of Ceballos. The canton Tisaleo is divided into two parishes: Tisaleo, an urban parish “cabecera cantonal” in the north; and, “Quinchicoto”, a rural parish located in the southeast of the canton. The limits of the canton of Tisaleo have not increased in 10 years. The analysis developed in this research allows us to understand Tisaleo as a decentralised and expansive model that uses more territory to achieve a moderate demographic growth; therefore, the following proposal proposes a spatial analysis through GIS software that delimits the areas of urban expansion of the canton of Tisaleo. It is proposed to carry out an urban growth model with a practical and reasonable standard, thus addressing the use of geographic information systems, maintaining the vision of cantonal development that focuses on: “agricultural, livestock and industrial development, balanced and sustainable growth, intercultural, participatory, inclusive and empowered societies that provide essential quality services and allow the inhabitants to live well”.\n\n\nLiterature review\n\nSpatial analysis, emerging since the 1950s and 1970s, addresses the need to examine temporal and spatial data, overcoming limitations in data sourcing and representation (Goodchild, 2005). This field, also known as cartographic modelling, involves interactive operations and commands that use maps for spatial decisions, focusing on processes. It reveals geographical structures and analyses formative processes, using concepts such as distance and spatial interaction (Pumain, 2004). Geographic space, according to Pulgarín (2007), is the living framework of an organism, while Castañeda (1997) defines it as the interaction between nature and society, differentiating into urban and rural contexts.\n\nSpatial measurement scales are a long-standing problem in spatial analysis; more details are available in the modifiable area unit (MAUP) topic. Landscape ecologists have developed a number of scale-invariant metrics for ecological aspects of fractal properties. More generally, scale-independent approaches to spatial statistical analysis are not widely accepted.\n\nSpatial sampling allows the identification of a limited number of localities in geographic space to faithfully measure phenomena affected by dependencies and heterogeneity. Dependencies show that, given a location, the value of different locations can be predicted, which does not require observations at both locations. Heterogeneity suggests that the relationship may vary spatially, making it impossible to rely on any degree of dependence outside what may be a small area. Basic spatial sampling schemes include the following modes: random, cluster, and system.\n\nDepending on a given spatial hierarchy (e.g., urban area, city, neighborhood), these basic schemes can be applied at multiple levels. Secondary data, such as the use of property values as a guide in spatial sampling schemes, can also be leveraged to measure educational attainment and income. Spatial models, such as autocorrelation statistics, regression, and interpolation, can also determine sample designs.\n\nThe perspectives of the definition of GIS, depends on its functionality, for the purposes of this study, we take the ability of these systems to create digital models of reality with the use of tools as discipline provides for these purposes.\n\nAccording to the National Center for Geographic Information and Analysis (NCGIA) of USA, 1990, taken by Del Bosque et al. in 2012, GIS is a System composed of hardware, software and procedures for the capture, management, manipulation, analysis, modeling and representation of georeferenced data, with the objective of solving complex planning and management problems (Del Bosque González, Fernández Freire, Martín-Forero & Pérez, 2012).\n\nGIS can be confused depending on essentially different issues, since the same acronym is used for discipline, project or software. The term GIS software corresponds to the program or set of programs that make it possible to develop the discipline and implement GIS projects, thus we speak of proprietary GIS Software, Free GIS of one or another commercial house (Del Bosque González, Fernández Freire, Martín-Forero & Pérez, 2012).\n\nThe canton of Tisaleo, according to its current Development and Land Use Plan, referred to the period 2019-2023, is a settlement that dates back more than 4 centuries with the name of San Miguel de Tisaleo, characterized until today by its fertile soil and agricultural vocation, in 1858 it was recognized as a civil parish and was elevated to canton on November 17, 1987. Tisaleo is located on the slopes of the Carihuairazo volcano, and at its eastern end is dissected by the crossing of the Pan-American Highway and the Camino Real, recognized as the old Inca Trail. It has an area of 59.64 km2. Its boundaries are: to the north with the canton of Ambato, to the south with the canton of Mocha, to the east with the cantons of Ambato, Cevallos and Quero and to the west with the canton of Ambato (Figure 1).\n\nTisaleo as a canton is divided into 2 parishes: Tisaleo and Quinchicoto; which in turn contains 15 hamlets: Alobamba, Chilco la Esperanza, El Calvario, La Unión, Quinchicoto Alto, San Diego, San Francisco, San Juan, San Luis, San Vicente, Santa Lucía Arriba, Santa Lucia Centro, Santa Lucia la Libertad, Santa Marianita and a large area designated as the Chimborazo Fauna Production Reserve (Figure 2).\n\nAccording to Article 241 of the Constitution of the Republic of Ecuador (2008), decentralized autonomous governments are obliged to plan their land use and management, while Articles 41 and 48 of the Organic Code of Planning and Public Finance explain that development and land use plans are instruments for strategic development decisions in the territory and their development and land use plans must be updated at the beginning of each administration.\n\nAnother tool that regulates territorial planning in Ecuador is the Land Use and Management Plan, according to Article 27 of the Ley Orgánica de Uso y Gestión del Suelo (2016): “In addition to the Organic Code of Planning and Public Finance, municipal and metropolitan decentralized autonomous governments will have a land use and management plan, which will incorporate structural and urban components”.\n\nThus, the municipal and metropolitan Decentralized Autonomous Governments have provisions and guidelines on the control and use of both urban and rural territory; in this way the Municipal Decentralized Autonomous Government of Tisaleo in 2019 and 2020 carried out the administrative processes for the update of its Development and Land Management Plan and its Land Use and Management Plan.\n\nIn this sense, the Autonomous Decentralized Municipal Government of Tisaleo has defined its land in 2 main categories in compliance with the current legal and technical regulations issued by the Superintendence of Land Use and Land Management, as shown in Figure 3.\n\nThe urban boundary defined in the Development and Land Management Plan for the period 2014-2019 and in the Land Use and Management Plan for the period 2020-2032, contains an area of 132.32 Hectares, which represents 2.22% of the total cantonal area. A priori in map 3 above, one can observe the presence of agricultural land that is still within the urban area defined since 2014.\n\nHowever, according to the studies that preceded this research, not all the urban area has all the services of the public system such as water, sewage or electricity, it is still worth noting that the percentage of occupation barely reaches the average of 20.74% covering the category of occupation in “formation” (Figure 4).\n\nSimilarly, the urban area of the parish of Quinchicoto was defined in the Development and Land Use and Management Plan for the period 2014-2019 and in the Land Use and Management Plan for the period 2020-2032, and covers an area of 25.95 hectares, which represents 0.44% of the total area of the canton. According to the Land Use and Management Plan for the period 2020-2032, the current occupation of Quinchicoto is 12.97%, i.e. the urban settlement is still in its infancy (GAD Municipal de Tisaleo, 2020).\n\nAccording to the Land Use and Management Plan in force for the canton of Tisaleo, two specific areas are defined as urban; Tisaleo as a city and the head of the parish Quinchicoto, which, according to the analysis of the Plan, the two do not exceed 25% of occupation, that is to say that they are still in formation.\n\nFor the same reason, the question arises as to how this urban growth has been developing. For the purposes of this research, we used current and existing tools such as satellite images of the years 2005, 2012 and 2020 (Figure 5, Google Earth, 2024).\n\nIf we analyze the percentage of growth based on the current urban limit, we obtain the following results: Table 1\n\nThe current urban boundary in relation to the urban area digitized in 2020, is oversized by 487% more than what reality indicates (Table 1), defined in relation to the concentration of housing that has been established since the base year which is 2005, this analysis is made in relation to the ordinance that defines the urban boundary does not match reality (Figure 6).\n\nIn the case of Quinchicoto, something similar happens, but due to the resolution of the satellite images and cloud coverage, it is not possible to homologate the process, in this sense, within the PUGS in force in the Gad Municipal de Tisaleo (2021).\n\n\nMethods\n\nThe methodology of this scientific research is based on a quantitative approach, using surveys to collect data to be analyzed statistically (Álvarez, 2021). Documents such as the Development and Land Use Plan of the canton of Tisaleo, the Land Use and Management Plan, files and reports of the canton were analysed. The relationship between the independent variable “spatial analysis” and the dependent variable “expansion of the urban area” was analysed.\n\nField research was carried out in the territory where the georeferencing of urban facilities and services was carried out, as well as a survey of the use given to the property. For the calculation of the present sample, a finite sample size of 1030 properties registered in the urban cadastre of the GAD Municipal del cantón Tisaleo was used, in order to obtain updated information with the reality of the inhabitants of the canton of Tisaleo.\n\nThis method is appropriate when the problem to be studied presents data that can be represented by mathematical models, allowing the elements of the research to be clear, defined and limited.\n\nThe study design is non-experimental and cross-sectional, since it is based on categories, concepts, variables, events or contexts without the direct intervention of the researcher, and observations and records are made at a single point in time. The research includes documentary, descriptive, explanatory and field components. The documentary research focuses on the search and analysis of secondary data, while the descriptive research is dedicated to present an actual interpretation of the results obtained, describing in detail the spatial analysis with GIS for urban sprawl (Baxendale & Buzai, 2011; Bernal, 2018; Bonham-Carter, 1994). The explanatory research seeks to understand the relationships between variables, and the field research was conducted in situ, collecting information individually in the canton of Tisaleo, focusing on the georeferencing of urban facilities and services. A finite sample size was used for a population of 1030 properties registered in the urban cadastre of the GAD Municipal del cantón Tisaleo (2020).\n\n\nResults\n\nThe Tisaleo canton, being located in the Ecuadorian highlands, contemplates the presence of topography and relief different from that of the Ecuadorian coast or Amazon, which is a component that can condition the location of human settlements, agricultural activities and, in itself, the territorial development of the towns.\n\nIn Figure 7 and Table 2, the predominant slopes are those classified between 12 and 25%, followed by those classified between 5 and 12%, which according to the definition of the CLIRSEN and MAGAP object catalogs in 2008 would determine that the relief of slopes in Tisaleo canton are slightly and moderately undulating reliefs, and by the classification of between 25-40% are strongly dissected reliefs (CLIRSEN, 2011).\n\nAn important structuring component to determine population and urban growth is water, in this case the canton of Tisaleo is located on the slopes of Carihuairazo, and has the presence of many streams, springs, streams, and lagoons; the same that dissert the relief and reduce the continuity of the villages in an extensive or regular way. All of these bodies of water flow into two main watersheds: the Ambato and Panchanlica rivers, which contribute to a larger water system, the Pastaza River (GAD Municipal de Tisaleo, 2020).\n\nAnother important component that can define or condition urban delimitation and growth are the natural protected areas, which are areas of land especially dedicated to the protection and maintenance of biological diversity, recognized by the State and managed through legal or other effective means (UICN, 1998). In the case of Tisaleo, 18.61% belongs to the Chimborazo Fauna Production Reserve, as shown in Figure 8. The decentralized autonomous municipal and metropolitan governments are responsible for defining and managing land use through their development and land use plans, as well as their land use and management plans: Forest Reserve Zones in water zones and the San Antonio water recharge zone.\n\nThe three types of reserves currently have human intervention, to the point that there are private properties within the Chimborazo Fauna Production Reserve, due to the transposition of adjudications and reserve declarations; and in addition to this, the georeferencing technologies of the Natural Areas cadastre and property cadastres are recent.\n\nIn the biophysical characterization component, one of the most important factors that determines urban growth and its delimitation with areas susceptible to natural hazards. According to the Secretariat of Risk Management, Tisaleo is located in areas susceptible to volcanic hazards, mass movements, drought and forest fires (Secretaría de Gestión de Riesgos, 2022).\n\nOne of the main risks is mass movements, as can be seen in Figure 9, which continues, susceptibility is concentrated in the foothills of the Carihuairazo and bodies of water, intersecting with infrastructure such as roads, towns, urban facilities, thus generating in the case of a natural event affecting infrastructure and equipment.\n\nAccording to the history of the canton, in 1698 there was a collapse of the Carihuairazo volcano, where landslides and mud deposits were recorded as a result of a strong tectonic earthquake. According to Vásconez (2009), these are still present today throughout the canton of Tisaleo, Quero and Ambato (Vásconez, 2009). As shown in Figure 10, taken from the work “Devastating mudflows triggered in the Carihuairazo volcano by the earthquake of June 20, 1698”.\n\nIn addition to these risks, the canton of Tisaleo has a low susceptibility to drought and a high susceptibility to forest fires in the paramo areas near the foothills of the Carihuairazo volcano (Figure 11).\n\nIn this sense, the biophysical structure of a territory is the important basis for determining its territorial growth; as indicated by Gómez Orea & Gómez Villarino (2013), both the carrying capacity of the ecosystems and the natural risks are causal for determining the carrying capacity of a space to carry out activities, be they conservation, production, urbanization, among others.\n\nGómez de Antonio (2003) mentions that endogenous resources, both natural and human, in addition to exogenous activities affect the distribution of territorial activities, but with an urban planning approach, it is the response to the construction of the city, its urban expansion and the classification and urban qualification of the land (Figure 12).\n\nThe Organic Law of Land Management, Land Use and Management in its fourth article issues the definition on a populated settlement and other territorial organizations; in this sense if the city and a populated settlement are related, this differs in that a city contains the necessary and ordered goods and services to generate the economic, political, social and cultural development of its citizens, and a settlement itself is a conglomerate of settlers who settle in a concentrated or dispersed way on a space or territory (LOOTUGS, 2018).\n\nThe organization of the populated settlements in the canton of Tisaleo, the subject of this study, are not differentiated, that is, according to the Development and Land Management Plan and the Land Use and Management Plan, there are currently 69 population centers, which according to data collected for this research are known as: “hamlets, sectors, communes or other names” (GAD Municipal de Tisaleo, 2020). With this background, it is concluded that the differentiation, delimitation or conceptualization of what can be considered as a city (urban) or populated settlement (urban or rural) cannot be defined by a law or manual, but rather with the individualized treatment of each territory of each canton, due to the exclusivity of the municipalities in defining the classification between urban and rural.\n\nErroneously, as reviewed in previous sections, the urban limits of Tisaleo and its rural parish of Quinchicoto are oversized, including agricultural and livestock areas without any housing use, and other sectors such as Alobamba, are still defined as rural, having a greater use and concentration of housing, goods, services and equipment than the parish of Quinchicoto (Figure 13).\n\nThe delimitation between urban and rural, under current regulations to generate a Land Use and Management Plan, are mainly the following variables: road network and transportation, water for human consumption, sewage, electric service, parks and squares, health facilities, education, social welfare, recreation and sports, security, and public administration. In this sense, for the purposes of this research, each of these factors was analyzed separately, as these are the ones that would delimit the urban expansion zones in the short, medium and long term.\n\nRegarding the road and transportation network, it converges in the characterization of the cantonal road network that can be differentiated by some indicators such as: annual average daily traffic, roughness, roadway, condition, width, works of art, among others; however, for the purposes of this study, the hierarchy, coverage of the road network, transportation routes and their equipment are analyzed; these characteristics are a vital part as a component of the urban development of a town, canton or country. The cantonal road network has a total length of 302.53 km and is composed of five types of roads: cobblestone, asphalt, concrete, stone and dirt. Dirt roads predominate with 165.78 km, representing 54.80%, followed by asphalt roads with a length of 91.01 km, representing 30.08%, and only 2% are cobblestone roads. Figure 15 shows where asphalt and cobblestone roads are concentrated, areas that are new for building new housing or plans (GAD Municipal de Tisaleo, 2020). Traffic and transportation management in the province of Tungurahua for the cantons of Baños, Cevallos, Mocha, Patate, Pelileo, Pillaro, Quero and Tisaleo, generate their own traffic and transportation plan, where they define a hierarchy of their roads as follows (Figures 14 & 15):\n\nTisaleo is connected by the Panamerican Highway E35 and articulated by secondary roads that connect with the cantons of Ambato, Cevallos and Mocha, and a countless number of third order roads that are paved and/or dirt roads. In terms of mobility, the Panamerican Highway and the secondary roads are currently being used as nodal roads, where all the traffic of the third order roads converge and are progressively becoming overcrowded with vehicles due to the increase in the number of vehicles. Regarding public transportation routes, the presence of the Pan-American Highway and secondary roads, this service and the infrastructure of bus stops are concentrated in these 2 types of roads; and mixed cabs complement the transportation coverage at the level of the entire canton (Empresa Pública de Mancomunidad de Tránsito de Tungurahua, 2017).\n\nA basic element that contributes to the growth of cities is the drinking water and sewerage service, in the case of Tisaleo, for these two elements of review, the existing information of the existing multifinalitarian cadastre in the Municipal GAD, having the following results:\n\nAt the cantonal level, the concentration of water and sewerage services coincides with the presence of asphalt and paved roads, i.e., when roads are increased, they go hand in hand with water and sewerage services. As can be seen in the following map (Figure 16).\n\nThe analysis was carried out with a universe of 16048 properties registered at the Head Office of Appraisals and Cadastre of the Municipal Government of Tisaleo, of which were selected based on the attributes of sewerage and water for human consumption; 52% of them have access to drinking water and 37% have sewerage; therefore, 37% have both water and sewerage.\n\nAnother important factor in determining the growth of urban areas is the provision of electricity service; since, in addition to water and sewage coverage and accessibility by roads and transportation, these are the basic services to encourage new construction of housing or commerce, in addition to biophysical and socioeconomic factors.\n\nElectric power coverage covers 51.66% of the existing properties in the canton, and there is an electric substation with the same name (Tisaleo) located in the north of the canton, in the Chilco La Esperanza hamlet; this station is part of the 500 kV transmission system and connects the new Coca Codo Sinclair and Sopladora projects (Figure 17).\n\nTherefore, it is the detail of the above elements that can determine the territory’s capacity to provide for the construction of housing or urban facilities in the short, medium or long term, but it is also convenient to analyze the coverage of public or private urban services such as education, health, social welfare, recreation and sports, and security.\n\nTo analyze the coverage of social and public services and facilities (Table 3), coverage is measured using radii of influence, with neighborhood, sector, zone, city or regional scope, and for each of the services and facilities there is a corresponding radius described in the following Table 3:\n\nThe relationship between public and social service facilities and their coverage depends on the existing demand of the population, i.e., in Ecuador and Latin America the causality for the construction of social service facilities does not depend on medium or long term planning but rather on the needs of the population; i.e., the construction of streets, housing and basic services increases faster than the construction of public and social service facilities.\n\nSocio-economic characterization:\n\nIn the last census of 2010 conducted by the Institute of Statistics and Census, it dates a number of 12,137 inhabitants, but for the year 2020 according to the same population growth data (1.80%) indicates a total of 14,317 settlers. Fifty-one percent of the population is female and 49% is male, and a quarter of the population is mostly young.\n\nTisaleo is an eminently agricultural canton, with agricultural activities distributed from the highest part with pastures for livestock, in the middle part with the production of short-cycle crops and in the lower part with fruit crops, taking advantage of its young economically active population, which represents 26.4% of the total EAP. According to data from its current cantonal development plan, 74.13% of its land has irrigation for its crops; as a result, agriculture and construction are the main sources of income for its inhabitants (GAD Municipal de Tisaleo, 2020).\n\nLand fragmentation is recognized as a cause of decreased production capacity and yields, according to population data within their current plans as of the date of this research; on the other hand, an important problem is that 40% of the arable layer is worn and degraded. In terms of agroindustrial initiatives, there have been few initiatives to improve the added value of their products and to technify the areas that are still purely productive (GAD Municipal de Tisaleo, 2020).\n\nProcess of interrelation between structuring elements of urban expansion in the canton of Tisaleo.\n\nHaving described the elements that structure and determine urban growth in a generalized way, territories and their endogenous and exogenous characteristics differ greatly within each province, each country and continent; it is impossible to compare one canton with another. In this sense, for this research we define which are the most common structuring elements with easily accessible information, and the relationship that these elements have in order to later analyze these variables and better define urban limits and their expansions.\n\nKnowing the information collected, its sources and scales are of vital importance to categorize it, weight it and evaluate whether or not it is feasible to use it within a spatial analysis with GIS software (Figure 18).\n\nThese three major groups contribute to the orderly urban growth of the canton of Tisaleo, but the degree of importance of these are very different, i.e. the causality between these parts from having a suitable biophysical area and out of natural risks in order to implement roads, services and equipment; for this reason these two major groups will be taken quantitatively, which are the biophysical structure and the public support system. In order to prioritize which of these factors has the greatest degree of intervention in urban expansion, a double-entry matrix was used, with the following evaluation criteria (Tables 4 & 5):\n\nOnce evaluated the importance between each variable, it coincides that, natural risk zones are considered as the most important factor that would determine urban growth, followed by hydrography and relief, in this way once a spatial analysis is performed will be the most suitable way the weighting of the variables and so that its value is the one that has the most interference in terms of planning an urban boundary and its growth.\n\n\nConclusions\n\nCities are dynamic, the constant demand for housing and the population’s need for a place to live have generated that rural soils, from productive soils to soils with susceptibility to natural risks, are populated. In the case of Tisaleo, according to this research, it has agricultural potential, although its connection with the canton of Ambato, which is the provincial capital, and because of its location on the Pan-American Highway, urban expansion has been occurring in a disorderly manner. Tisaleo, located in the inter-Andean zone of Ecuador, on the slopes of the Carihuairazo volcano, has heterogeneous bio-physical characteristics that determine the distribution of its settlements, as well as a very high coverage of basic services in relation to the average for the country and the province of Tungurahua. According to the surveys conducted, housing occupancy within the investigated properties ranges from 2 to 3 people, thus having an under-occupation of the land that could be concentrated in areas that are suitable for housing and commerce.\n\nEach of these elements has different importance and influence on the territory in terms of the land’s suitability for urban growth, since a biophysical element is more decisive than an infrastructure element such as a road or electric power. The synergy that marks the construction of new roads leads in this case that the new constructions are directed towards where the roads are being opened and improved.\n\nWith all the data and their degree of importance, one of the tools used to interact and intersect their variables involves the use of geographic information systems software, which more than interrelating their alphanumeric data, also interrelates geographically georeferenced data, thus adding spatial coincidences in terms of the characteristics of territory that would improve the conditions where new urbanization and construction of housing, stores and equipment can be carried out. In the case of Tisaleo, where the coincidences of aptitudes for urban growth converge, it coincides with the areas currently considered as urban, which are Tisaleo and Quinchicoto, but its limit is oversized, that is, it includes areas that do not have the aptitudes to be urbanized, as well as areas such as Alobamba and Santa Lucia Arriba that are considered as rural, but have all the characteristics to be considered as urban.",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nZenodo: GIS integration for spatial analysis of urban expansion in Tisaleo canton (Ecuador), https://zenodo.org/records/12702689 (Chiriboga Zamora et al., 2024).\n\nThe cadastral data for this project have been obtained from: https://www.tisaleo.gob.ec/\n\nThe maps have been produced by the authors from: Secretaría de Gestión de Riesgos de Ecuador (https://www.gestionderiesgos.gob.ec/), Ministerio de Ambiente, Agua y Transición Ecológica (https://www.ambiente.gob.ec/), Instituto Geográfico Militar de Ecuador (https://www.geoportaligm.gob.ec/portal/).\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\n\nReferences\n\nÁlvarez R: Metodología de la Investigación: Operacionalización de Variables. Colombia: McGraw-Hill; 2021.\n\nBaxendale C, Buzai GD: Análisis Espacial con Sistemas de Información Geográfica. Aportes de la Geografía para la elaboración del Diagnóstico en el Ordenamiento Territorial. Fronteras. 2011; 10: 25–38.\n\nBernal A: Modelo Espacial-Temporal para Sistemas Dinámicos Discretos en Sistemas de Información Geográfica. México: 2018. Doctoral Tesis.\n\nBonham Carter G: Geographic Information Systems for geoscientists: Modelling with GIS. Elsevier; 1994.\n\nCastañeda J: Geografía y medio ambiente: Una relación interdependiente. Editorial Universitaria; 1997.\n\nChiriboga Zamora PA, Tapia Hermida LX, Romero Flores ML, et al.: GIS integration for spatial analysis of urban expansion in Tisaleo canton (Ecuador). [Data set]. Zenodo. 2024. Publisher Full Text\n\nCLIRSEN. Centro de Levantamientos Integrados de Recursos Naturales por Sensores Remotos: Catálogo de objetos y clasificación de pendientes para el cantón Tisaleo.2011.\n\nConstitución de la República del Ecuador: 2008. Reference Source\n\nDel Bosque González I, Fernández Freire C, Martín-Forero Morente L, et al.: Los Sistemas de información geográfica y la investigación en Ciencias Humanas y Sociales. Madrid: CECEL-CSIC; 2012. Reference Source\n\nEmpresa Pública de Mancomunidad de Tránsito de Tungurahua: Informe de movilidad y transporte en el cantón Tisaleo. Ecuador: Tungurahua; 2017.\n\nESRI: ArcGIS Desktop.2018. Reference Source\n\nGAD Municipal de Tisaleo: Plan de Desarrollo y Ordenamiento Territorial. Plan de Uso y Gestión del Suelo. Tisaleo: 2020. Reference Source\n\nGAD Municipal de Tisaleo: Plan de Uso y Gestión del Suelo (PUGS).2021. Reference Source\n\nGoogle Earth Pro (versión 7.3.3): Imágenes de satélite obtenidas el 15 de febrero del.2024. Reference Source\n\nGómez de Antonio M: Un modelo para cuantificar el impacto de las variables territoriales en el crecimiento de la renta per capita de las provincias españolas. Estudios Regionales. 2003; pp. 107–132.\n\nGómez Orea D, Gómez Villarino A: Ordenación Territorial. Madrid: Mundiprensa; 2013.\n\nGoodchild MF: The future of the spatial sciences. J. Geogr. Syst. 2005; 7(1): 3–9. Publisher Full Text\n\nIGM. Instituto Geográfico Militar: Información espacial.2014. Reference Source\n\nIGM. Instituto Geográfico Militar: Información espacial.2022. Reference Source\n\nLey Orgánica de Ordenamiento Territorial, Uso y Gestión de Suelo: 2016. Reference Source\n\nMAE. Ministerio del Ambiente: 2020. Reference Source\n\nMinisterio de Ambiente, Agua y Transición Ecológica: 2021. Reference Source\n\nPulgarín MR: El estudio del espacio geográfico, ¿posibilita la integración de las ciencias sociales que se enseñan? Revista Educación y Pedagogía. 2007; 14(34): 179–194.\n\nPumain D: Análisis espacial en geografía. Espacio Geográfico. 2004; 26(1): 15–24.\n\nRuiz Pozo LE: Los actores sociales en la construcción de la política de vivienda: cinco años de acción del contrato social por la vivienda en Ecuador 2005-2010. Tesis de Maestría. Flacso Ecuador; 2011.\n\nLOOTUGS. Superintendencia de ordenamiento territorial: Glosario de conceptos y Definiciones de la ley orgánica de ordenamiento territorial, uso y gestión del Suelo.2018. Reference Source\n\nSecretaría de Gestión de Riesgos: Informacion espacial. 2021. Reference Source\n\nSecretaría de Gestión de Riesgos: Informacion espacial. 2022. Reference Source\n\nUICN: Directrices para las categorías de gestión de áreas protegidas. Gland, Suiza y Cambridge, Reino Unido: UICN; 1998.\n\nVásconez R: Devastadores flujos de lodo disparados en el volcán Carihuayrazo por el terremoto del 20 de junio de 1698. Revista Politécnica. 2009; 30(1): 92–111."
}
|
[
{
"id": "335661",
"date": "13 Nov 2024",
"name": "Moh Dede",
"expertise": [
"Reviewer Expertise Landscape dynamics",
"environmental management",
"sustainable tourism",
"geography of crime",
"geography education",
"social studies"
],
"suggestion": "Not Approved",
"report": "Not Approved\n\ninfo_outline\nAlongside their report, reviewers assign a status to the article:\n\nApproved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested\n\nApproved with reservations\nA number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.\n\nNot approved Fundamental flaws in the paper seriously undermine the findings and conclusions\n\nDear authors, The manuscript presents a spatial analysis of urban expansion in Tisaleo Canton, Ecuador, using GIS. While the topic holds significant relevance in urban studies and spatial planning, the current draft has several key areas requiring improvement to enhance clarity, depth, and academic rigor. Below, I provide detailed feedback on various sections of the manuscript.\nThe title, \"GIS Integration for Spatial Analysis of Urban Expansion in Tisaleo Canton (Ecuador),\" appears somewhat redundant with the combined use of \"GIS\" and \"spatial.\" Since the analysis inherently involves spatial components, the inclusion of both terms may be unnecessary. I suggest simplifying the title by omitting \"GIS\" and using \"Spatial Analysis of Urban Expansion in Tisaleo Canton (Ecuador)\" for a more concise and focused title. The abstract lacks a clear background to frame the significance of the study, particularly regarding the rationale behind the chosen area and the primary data sources used. Additionally, multi-parameter assessments are central to suitability analysis but are not mentioned in the abstract. Including this information would help readers better understand the study's scope and methodology.\n\nThe introduction currently reads more as a summary of Tisaleo Canton rather than a detailed introduction to the research problem or the broader urban expansion issues it aims to address. This section should be expanded to provide a comprehensive problem statement and contextual background on urban expansion challenges, ideally citing relevant studies to substantiate the significance of the work. The literature review appears shallow and lacks depth, as well as organization. It blends situational descriptions of the study area with general literature, which can be confusing for readers. Furthermore, maps are provided in the original language without English translations for symbols, which hinders comprehension. The literature review should focus on existing studies relevant to urban expansion and spatial analysis, moving any study area details to a separate section if necessary. The methodology section lacks the level of detail required to understand the analytical process fully. For example, if a multi-criteria decision-making model is used, it should clearly explain the weight and scoring systems applied to each variable. Furthermore, the source of the \"relative weight\" for variables should be clarified—whether derived from established decision-making models or calculated through another technique. A more explicit breakdown of each step in the spatial analysis would strengthen this section considerably. The results and discussion section lacks systematic presentation and coherence. Maps and figures are still presented in the original language rather than English, making it difficult for non-native readers to interpret the results. Additionally, the study’s main objective—urban expansion analysis—seems overshadowed by environmental and socioeconomic parameters, which do not directly tie back to the expansion theme. The discussion would benefit from a stronger analytical narrative and supportive argumentation to clarify findings. The conclusion does not sufficiently reflect the study’s tentative hypotheses or validate them with data. It would be more impactful if it clearly outlined the patterns, drivers, and extent of urban expansion observed, connecting back to the research objectives. A well-structured conclusion would enhance the paper’s coherence and provide a more meaningful takeaway for readers. The references are predominantly local sources, limiting the study's broader relevance. Expanding the reference list to include international studies on urban expansion and spatial analysis would provide a more comprehensive foundation and strengthen the manuscript's scholarly contribution.\nIn conclusion, while this study has a promising subject, addressing the comments above will considerably improve its academic quality and coherence.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nIs the work clearly and accurately presented and does it cite the current literature? Partly\n\nIf applicable, is the statistical analysis and its interpretation appropriate? No\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\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? Partly",
"responses": []
},
{
"id": "335669",
"date": "21 Nov 2024",
"name": "Muhammad Salem",
"expertise": [
"Reviewer Expertise Urban Planning",
"Land Use management and GIS"
],
"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 offers an insightful case study on urban expansion in Tisaleo, Ecuador, with potential contributions to understanding land suitability in small urban centers. However, the study would benefit from addressing the methodological gaps and refining its focus on how GIS methods specifically inform urban planning challenges. My suggestions for improvements are as follows:\nThe introduction should begin with general information about urban expansion and the relevance of GIS-based land suitability analysis before focusing specifically on Tisaleo as a case study. Additionally, while the study presents Tisaleo as an interesting case, the introduction doesn't clearly explain why studying Tisaleo’s urban expansion is particularly valuable or how the findings contribute to broader urban planning issues. A concise statement of the specific research objectives or questions would provide stronger context. Highlighting how GIS methods support urban expansion studies in small urban centers like Tisaleo would also reinforce the value of this case study. The discussion on scale should be explicitly tied to the case study’s focus on urban expansion in Tisaleo. Explaining the significance of scale in interpreting urban boundaries, population densities, and infrastructure distribution would make this section more relevant to the research context. While the paper provides useful geographical context on Tisaleo, I recommend reducing excessive background details about its general geography. Instead, prioritize discussing factors that directly affect urban growth, such as infrastructure, socio-economic conditions, and local land-use policies. The case study approach benefits from providing specific methodological details, but the paper does not elaborate on the sampling method (e.g., random sampling, stratified sampling) for the stated sample size of 1,030 properties. Details about the survey design, such as the type of questions asked and the data collected, are missing. Briefly explaining the survey’s primary focus (e.g., resident perceptions of urban growth or utility service usage) The paper would benefit from discussing how restrictions in protected areas influence urban expansion in Tisaleo Figure 5: Combining the various boundaries into a single figure with a clear legend would make interpreting and comparing the data easier. Table 1: The growth percentages should be related to the previous urban boundary area, rather than the initial boundary, to provide a more accurate representation of incremental growth trends. Figures: To ensure accessibility and clarity, all legends and labels should be provided in English.\n\nIs the background of the case’s history and progression described in sufficient detail? Partly\n\nIs the work clearly and accurately presented and does it cite the current literature? 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? No\n\nAre the conclusions drawn adequately supported by the results? Partly\n\nIs the case presented with sufficient detail to be useful for teaching or other practitioners? No",
"responses": [
{
"c_id": "13294",
"date": "07 Feb 2025",
"name": "PATRICIA CHIRIBOGA",
"role": "Author Response",
"response": "Dear members of the editorial team, We appreciate the review and comments provided by the reviewer. We agree with the observations and are willing to make the suggested adjustments to our manuscript. We remain attentive to your indications on the process to follow in order to implement the changes correctly and comply with the requirements of the journal. We thank you for your guidance and look forward to your instructions."
}
]
}
] | 1
|
https://f1000research.com/articles/13-1235
|
https://f1000research.com/articles/13-1234/v1
|
15 Oct 24
|
{
"type": "Study Protocol",
"title": "Effect of immediate dentin sealing on the fracture strength of indirect posterior restorations:Systematic review and meta-anlysis protocol.",
"authors": [
"Yosra Gassara",
"Rim Kallala",
"Rihab Dakhli",
"Sarra Nasri",
"Nourhen Klach",
"Belhassen Harzallah",
"Rim Kallala",
"Rihab Dakhli",
"Sarra Nasri",
"Nourhen Klach",
"Belhassen Harzallah"
],
"abstract": "Background Immediate Dentin Sealing (IDS) is a technique that applies an adhesive layer immediately after tooth preparation, prior to the placement of indirect restorations. This method is gaining attention due to its potential to improve the bond strength and mechanical properties of restorations, particularly in the posterior region where restorations endure significant masticatory forces. The objectif of this systematic review and meta-analysis is to evaluate the effect of IDS on the fracture strength of indirect posterior restorations.\n\nMethods Following PRISMA guidelines, a comprehensive literature search was conducted in four databases: Web of Science, Scopus, Cochrane Library, and PubMed. Inclusion criteria focused on in vitro studies involving human teeth with indirect posterior restorations, published between 2014 and 2023. Studies using IDS were compared to those using conventional methods. The risk of bias was assessed using the Cochrane Collaboration’s tool, and a meta-analysis was performed with a random-effects model. The standard mean difference and 95% confidence intervals were calculated to compare fracture strength, with I2 statistics assessing heterogeneity. Forest and funnel plots were employed to visualize results and publication bias, respectively.\n\nDiscussion The results indicate that IDS generally enhances the fracture strength of indirect posterior restorations, particularly with ceramic materials like lithium disilicate. However, the effectiveness of IDS varies depending on the material and restoration type. While some studies demonstrated improved fracture resistance with IDS, others showed minimal benefit, especially with composite restorations. Additionally, IDS improved marginal adaptation and internal fit but increased the risk of severe failures, such as root fractures.\n\nSystematic review registration PROSPERO: CRD42024584545 (Registered on 08/09/2024).",
"keywords": [
"Fracture Strength",
"Endocrown",
"Overlay",
"occlusal veneer",
"Indirect restoration",
"Inlay",
"Onlay",
"immediate dentin sealing"
],
"content": "Introduction\n\nImmediate Dentin Sealing (IDS) has emerged as a highly influential technique in the field of restorative dentistry, particularly in the context of indirect posterior restorations.1–4 This technique involves the application of an adhesive layer immediately after tooth preparation and before the final restoration is placed.5,6 The primary goal of IDS is to optimize the bond strength between the tooth and restoration, while simultaneously preserving the vitality of the tooth by creating a durable seal. In contrast to delayed dentin sealing, which occurs after temporization, IDS is performed in the initial stages of the restorative process, leading to enhanced adhesion and improved long-term outcomes.7\n\nThe technique has gained significant attention for its potential to improve the mechanical properties of partial restorations, particularly those located in the posterior region of the mouth, where restorations are exposed to substantial masticatory forces.8–11 These forces make the posterior region especially vulnerable to mechanical failure, making it critical for restorations in this area to exhibit both high durability and fracture resistance. For these reasons, it is important to investigate how IDS impacts the long-term success of indirect posterior restorations, especially in terms of their ability to withstand the stresses of everyday function.8\n\nDespite its growing popularity, the effects of IDS on fracture strength remain a topic of debate. While several studies suggest that IDS enhances the fracture resistance of indirect restorations, discrepancies exist depending on factors such as the materials used, the specific restoration type, and the methods employed. Therefore, a systematic review and meta-analysis are necessary to consolidate the existing evidence and provide a clear understanding of IDS’s role in improving fracture strength.12,13\n\nThis systematic review and meta-analysis aim to assess the effect of IDS on the fracture strength of indirect posterior restorations, offering a thorough evaluation of current evidence.\n\n\nProtocol\n\nThis systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. It will also comply with the Methodological Expectations of Cochrane Intervention Reviews and the Cochrane Handbook for Systematic Reviews of Interventions. The review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42024584545, as of September 8, 2024.\n\nPrimary objectives\n\nSpecify the effect of immediate dentin sealing on the fracture strength of indirect posterior restorations.\n\nSecondary objectives\n\nDescribe the benefits of IDS in posterior partial restorations\n\nPresent the mechanical properties of these restorations.\n\nSpecifying the impact of IDS on their fracture resistance.\n\nThe PICOS framework (Participants, Intervention, Comparison, Outcome, Study Design) will be used to organize the eligibility criteria, which is intended to emphasize the key components of the research question.\n\nThe research question for this systematic review is:\n\nThe PICO question is: What is the effect of immediate dentin sealing (intervention) on the fracture strength (outcome) of indirect posterior restorations (population) compared to delayed dentin sealing (comparison)?\n\n• Types of participants:\n\nThis systematic review will focus on teeth restored with indirect posterior restoration: Endocrown, Overlay, occlusal veneer, Inlay and Onlay.\n\n• Types of interventions:\n\nThe intervention of interest is immediate dentin sealing (IDS). This technique involves sealing the dentin immediately after tooth preparation, before the indirect restoration is placed.\n\n• Types of outcomes:\n\nThe primary outcome of interest is the fracture strength of the indirect posterior restorations.\n\n• Measures of effect:\n\nThe main outcome, fracture strength, will be measured using either the risk ratio (relative risk) or odds ratio, depending on the type and availability of the data from the included studies. Meta-analysis will be performed if sufficient homogeneous data is available.\n\n• Study types:\n\nThis review will include both in vivo and in vitro studies that assess the effect of immediate and delayed dentin sealing on fracture strength. Both randomized controlled trials (RCTs) and observational studies with a comparative design will be considered.\n\nStudies will be excluded if they meet any of the following criteria:\n\nStudies involving indirect anterior restorations.\n\nStudies with animal models.\n\nInterventions on temporary teeth.\n\nTwo independent searchers, Y.G. and R.K. will search four different databases: Web of Science, Scopus, Cochrane library and PubMed.\n\nThey will perform a manual search and meticulously reviewed the reference lists of the studies included in this review to identify eligible ones. Additionally, electronic searches in databases will conduct using a combination of mesh terms (Table 1).\n\nTo select studies, duplicates will be removed. Titles and abstracts will be reviewed by the two investigators, and studies that do not meet the inclusion criteria will be excluded.\n\nThe methodological quality of the included studies will be assessed using the Cochrane Collaboration’s risk of bias tool, a standard method for evaluating biases in clinical research. This assessment will be done using Review Manager software (RevMan, version 5.4). Each type of bias, such as selection, performance, and detection bias, will be evaluated individually. The risk of bias for each domain will be rated as “low,” “unclear,” or “high” according to Cochrane guidelines. An overall rating will then be assigned to summarize the risk of bias for each study.\n\nData from the included articles will be collected by one author (Y.G.), while a second researcher (R.K.) will review all the extracted data. The collected data will include: the first author, year, type of study, sample characteristics, IDS technique used in each study, and fracture strength values.\n\nThe meta-analysis will evaluate the fracture strength of indirect posterior restorations (inlays, overlays, occlusal veneers) by comparing conventional methods to the immediate dentin sealing (IDS) method. Studies that contrast IDS with conventional methods will be included. Data analysis will be performed using RevMan software (version 5.4). The standard mean difference with a 95% confidence interval will be applied, andthe I2 statistic will assess heterogeneity by measuring the percentage of variation across studies caused by true differences rather than chance. It helps determine if differences in study populations, methods, or interventions explain the variability. Due to the variability in immediate dentin sealing (IDS) techniques, types of restorations, and methodologies employed across the included studies, a random effects model will be used for the meta-analysis. This model is appropriate in this context as it accounts for the inherent differences among studies, allowing for a more accurate estimate of the overall effect size.\n\nTo visually represent the results of the meta-analysis, forest plots will be generated. These plots will display the individual study outcomes along with the overall pooled effect, providing a clear illustration of the results and the degree of consistency among the studies. Additionally, funnel plots will be employed to evaluate the potential for publication bias. By plotting the effect sizes of the studies against their standard errors, funnel plots can help identify any asymmetry that may suggest selective reporting or other biases affecting the literature.\n\n\nDiscussion\n\nIDS generally enhances the fracture strength of indirect posterior restorations, especially with ceramic materials like lithium disilicate.12 However, its effectiveness varies depending on the material and type of restoration.14,15 While many studies report improved fracture resistance with IDS, others show only modest benefits, particularly in composite restorations.12 Additionally, IDS contributes to superior marginal adaptation and internal fit but may also elevate the risk of severe failures, such as root fractures.16,17\n\nThis review serves as a valuable resource for clinicians, offering guidance when restoring posterior teeth with indirect restorations.\n\nEthical approval is not required for this systematic review. The authors plan to present the results at relevant conferences and publish the findings in a peer-reviewed journal, following open science practices.\n\nThe protocol of this systematic review was submitted to PROSPERO registry on 08th September, 2024 (CRD42024584545).",
"appendix": "Data availability\n\nNo data are associated with this article.\n\nFigshare. PRISMA-P checklist for Effect of immediate dentin sealing on the fracture strength of indirect posterior restorations: Systematic review and meta-analysis Protocol. DOI: https://doi.org/10.6084/m9.figshare.27143277.v1 18\n\nThe project contains the following dataset:\n\n• PRISMA-P-checklist.docx\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0)\n\n\nReferences\n\nHofsteenge JW, Hogeveen F, Cune MS, et al.: Effect of immediate dentine sealing on the aging and fracture strength of lithium disilicate inlays and overlays.\n\nAbdulsattar YH, Kadhim AJ: Effect of immediate dentin sealing on the fracture strength of indirect overlay restorations using different types of luting agents: A comparative in vitro study. J. Conserv. Dent. Endod. 2023; 26: 434–440. PubMed Abstract | Publisher Full Text\n\nMagne P, Kim TH, Cascione D, et al.: Immediate dentin sealing improves bond strength of indirect restorations. J. Prosthet. Dent. 2005; 94: 511–519. PubMed Abstract | Publisher Full Text\n\nMueller B, Pilecco RO, Valandro LF, et al.: Effect of immediate dentin sealing on load-bearing capacity under accelerated fatigue of thin occlusal veneers made of CAD-CAM glass-ceramic and resin composite material. Dent. Mater. 2023; 39(4): 372–382. PubMed Abstract | Publisher Full Text\n\nOliveira EG, Mota GA, Borges LH, et al.: Influence of immediate dentin sealing techniques on cuspal deflection and fracture resistance of teeth restored with composite resin inlays. Oper. Dent. 2014; 39(1): 72–80. PubMed Abstract | Publisher Full Text\n\nMagne P, Schlichting LH, Maia HP, et al.: In vitro fatigue resistance of CAD/CAM composite resin and ceramic posterior occlusal veneers. J. Prosthet. Dent. 2010; 104: 149–157. PubMed Abstract | Publisher Full Text\n\nOzer F, Batu Eken Z, Hao J, et al.: Effect of immediate dentin sealing on the bonding performance of indirect restorations: A systematic review. Biomimetics (Basel). 2024; 9(3): 182. PubMed Abstract | Publisher Full Text | Free Full Text\n\nOliveira DC, et al.: Influence of glycerin coating on the bond strength of resin-dentin interfaces. J. Adhes. Dent. 2003; 5(4): 309–315.\n\nSaadeddin N, Al-Khalil MA, Al-Adel O: Effect of immediate dentin sealing on the fracture strength of lithium disilicate ceramic onlays. Swiss Dent. J. 2022; 132: 482–489. PubMed Abstract | Publisher Full Text\n\nSchlichting LH, Maia HP, Baratieri LN, et al.: Novel-design ultra-thin CAD/CAM composite resin and ceramic occlusal veneers for the treatment of severe dental erosion. J. Prosthet. Dent. 2011; 105: 217–226. PubMed Abstract | Publisher Full Text\n\nTeche FP, Valenzuela EBS, Tavares JG, et al.: Immediate dentin sealing influences the fracture strength of ultrathin occlusal veneers made of a polymer-infiltrated ceramic network. J. Mech. Behav. Biomed. Mater. 2022; 133: 105331. PubMed Abstract | Publisher Full Text\n\nvan den Breemer CRG , Özcan M, Cune MS, et al.: Effect of immediate dentine sealing on the fracture strength of lithium disilicate and multiphase resin composite inlay restorations. J. Mech. Behav. Biomed. Mater. 2017; 75: 92–99.\n\nShafiei F, Aghaei T, Jowkar Z: Effect of proanthocyanidin-mediated immediate and delayed dentin sealing on the strength of premolars restored with composite resin inlay. J Clin Exp Dent. 2020; 12(3): e235–e241. Publisher Full Text\n\nSignore A, Benedicenti S, Covani U, et al.: A 4- to 6-year retrospective clinical study of cracked teeth restored with bonded indirect resin composite onlays. Int. J. Prosthodont. 2007; 20: 609–616. PubMed Abstract\n\nAndrade JP, Stona D, Bittencourt HR, et al.: Effect of different computer-aided design/computer-aided manufacturing (CAD/CAM) materials and thicknesses on the fracture resistance of occlusal veneers. Oper. Dent. 2018; 43: 539–548. PubMed Abstract | Publisher Full Text\n\nAshy LM, Marghalani H, Silikas N: In vitro evaluation of marginal and internal adaptations of ceramic inlay restorations associated with immediate vs delayed dentin sealing techniques. Int. J. Prosthodont. 2020; 33: 48–55. PubMed Abstract | Publisher Full Text\n\nSchenke F, Hiller K, Schmalz G, et al.: Marginal integrity of partial ceramic crowns within dentin with different luting techniques and materials. Oper. Dent. 2008; 33: 516–525. PubMed Abstract | Publisher Full Text\n\nGassara Y: PRISMA-P checklist for Effect of immediate dentin sealing on the fracture strength of indirect posterior restorations: Systematic review and meta-analysis Protocol. Dataset. figshare. 2024. Publisher Full Text"
}
|
[
{
"id": "344743",
"date": "23 Jan 2025",
"name": "Dinesh Rokaya",
"expertise": [
"Reviewer Expertise Dental Biomaterials",
"Prosthetic Dentistry"
],
"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 done to evaluate the effect of IDS on the fracture strength of indirect posterior restorations.\nAbstract: The spelling of the Objective is a mistake. Please correct. The Introduction presents the background and Method explains in detail. PICOS framework (Participants, Intervention, Comparison, Outcome, Study Design is also clear.\nDoes the IDS affect the bonding of the ceramic?\nMore discussion is needed. Discuss with similar previous studies.\n\nIs the rationale for, and objectives of, the study clearly described? Partly\n\nIs the study design appropriate for the research question? Yes\n\nAre sufficient details of the methods provided to allow replication by others? Yes\n\nAre the datasets clearly presented in a useable and accessible format? Yes",
"responses": []
}
] | 1
|
https://f1000research.com/articles/13-1234
|
https://f1000research.com/articles/12-929/v1
|
03 Aug 23
|
{
"type": "Research Article",
"title": "Container buildings used for residential and business purposes in Johannesburg, South Africa and potential heat-related health risks",
"authors": [
"Tanganedzeni Mfamadi",
"Kimberley Chivimbo",
"Philistase Mogadime",
"Shalin Bidassey-Manilal",
"Thandi Kapwata",
"Natasha Naidoo",
"Caradee Y Wright",
"Tanganedzeni Mfamadi",
"Kimberley Chivimbo",
"Philistase Mogadime",
"Shalin Bidassey-Manilal",
"Thandi Kapwata",
"Natasha Naidoo"
],
"abstract": "Background: Outdoor and indoor air temperature affects human health and wellbeing. Climate change projections suggest that global temperatures will continue to increase and this poses a threat to health. Housing that can protect humans from the adverse effects of temperature is essential, especially in the context of climate change.\nMethod: In this cross-sectional study, we measured indoor temperature inside shipping containers comprising a seven-storey block of apartments and businesses in Johannesburg, South Africa. We assessed indoor temperature and relative humidity; evaluated measured temperatures in relation to thresholds known to be associated with adverse health risks; and sought to understand heat-health perceptions and symptoms of people living and working in shipping container units.\nResults: Median indoor apparent temperature (AT) (a combination of temperature and relative humidity) was 16 °C with values ranging from 6 °C (observed at 8:00) to 42 °C (observed at 17:00). Insulated units had temperatures between 2°C and 9°C cooler than uninsulated units. Heat-health risks from AT exposure were likely in all units, although there was variation in the number of occurrences that AT measurements exceeded the four symptom bands of caution, extreme caution, danger and extreme danger. Some participants believed that their units were hot during hot weather and most people opened windows or did nothing during hot weather. Few participants reported experiencing adverse heat-health impacts, except for experiencing headaches (n=62, 58%) and feeling tired or weak (40%).\nConclusion: Container units should be insulated and have adequate windows for ventilation when used for residential and commercial purposes, especially in hot climates. Awareness regarding heat-health risks of living and working in hot spaces needs to be done, especially in the context of repurposed container units.",
"keywords": [
"Climate change",
"Environmental health",
"Temperature",
"Thermal comfort",
"Urban area"
],
"content": "Introduction\n\nImproved housing conditions can prevent disease, reduce poverty, and increase quality of life.1 Adequate, safe housing is essential in the current global context of urbanisation, ageing populations, and climate change. In South Africa, around 80% of the population (of around ~60 million people) live in formal dwellings, 11% live in informal dwellings such as shacks and 4% live in traditional dwellings (the remaining 5% remains unknown.2 Among the formal dwellings are the government-provided, low-cost housing or Reconstruction and Development Programme (RDP) housing that attempts to give every South African a home. In recent years, initiatives by developers have seen an increase in the use of shipping containers to provide low-cost dwellings for South Africans who earn little to afford other types of formal dwellings, beside government housing. The shipping containers have been combined as a single storey or stacked to make a multi-storey block of apartments. In wealthier countries, shipping containers have been used as a sustainable housing option, sometimes called an ‘eco-pod’.3 This form of housing has also been used during emergency relief after extreme weather events displace people from their homes, as was the case in the Philippines.4 Similarly, following Hurricane Katrina in 2005, the Christchurch earthquake in 2011 and the Victoria (Australia) Black Saturday bushfires in 2009, shipping container dwellings were used to temporarily house displaced populations.5\n\nOf importance when making use of shipping containers as places to live or work is ensuring that the temperature inside the container is kept stable, thermally appropriate, and suitable for human habitation. Temperature measurements made inside shipping containers while they are on ships have shown that temperatures may exceed 60°C.6 Therefore, indoor temperatures in shipping containers may pose a challenge for their use as dwellings, especially in hot climates. Elrayies7 assessed thermal performance of shipping container architecture in hot and humid Port Said, Egypt and found indoor temperatures exceeded 44°C in some units, depending on the type of insulation applied (foam performed better than rock wool, wool, or straw). In the Philippines, different types of insulation such as foam and fibreglass batting did not improve the indoor thermal conditions of the shipping containers in a tropical (hot and humid) climate.4\n\nNo measurements have been made of temperature inside shipping containers converted into residences or business in South Africa, although, temperatures have been measured inside shipping container classrooms in Johannesburg, South Africa and were found to exceed 40°C during summer months.8 Therefore, we aimed to measure indoor temperatures inside shipping containers comprising a seven-storey block of apartments and businesses in Johannesburg, South Africa. There were three study objectives: 1) to assess temperature inside shipping container units used as dwellings and places of business; 2) to evaluate measured temperatures in relation to thresholds known to be associated with adverse health risks; and 3) to understand heat-health perceptions and symptoms of people living and working in shipping container units. These findings are important to inform policymaking and health awareness campaigns related to living and working in shipping containers in hot climates.\n\n\nMethods\n\nWe applied the STROBE reporting guideline to plan and execute this study which was a cross-sectional study conducted in the suburb of Maboneng located in the City of Johannesburg, South Africa. Maboneng is a mixed-use neighbourhood within the central business district of the city. Here, there is a building made of 140 shipping containers (Figure 1) repurposed into 107 units that are either residential apartments (n=103) or businesses (n=4). We aimed to install temperature loggers in ten units from the 12 September to 25 September 2021 after obtaining permission from the owner of the building and the tenants/owners of the units. We also administered a short survey questionnaire to occupants of the units after obtaining their informed consent.\n\n(Photo credit: Driveline Studios).\n\nResearch ethics clearance was obtained from the University of Johannesburg Faculty of Health Sciences Research Ethics Committee (REC-1055-2021, 4 June 2021).\n\nWritten informed consent was obtained from all participants for participation in the study as well as publication of their self-reported data.\n\nTemperature loggers called iButtons were installed in the container units to measure indoor temperature. iButtons are small, portable sensors that record temperature and relative humidity onboard for download after monitoring. iButtons were installed against a piece of furniture like a cupboard away from the walls in each of the ten containers from the 12 September to 25 September 2021. This approach was made instead of suspending the iButton from the ceiling to minimise intrusion of the instrument to the inhabitant and has been done successfully before.9 Data were downloaded as.txt files and imported into R software10 for analysis.\n\nAmbient temperature and relative humidity data for the meteorological station closest to the container building were obtained from the South African Weather Service (SAWS). Wind data were also available. Meteorological data were provided at 10-minute intervals which were converted to hourly interval calculations.\n\nIndoor and ambient temperature and relative humidity data were used to calculate indoor and outdoor apparent temperature (AT), respectively. AT is a calculation that considers ‘real-feel’ temperature and is an indicator of thermal comfort as well as gives an indication of potential heat-health impacts based on defined thresholds.11 AT was calculated as follows:\n\nWhere:\n\nTa = dry bulb temperature (°C)\n\ne = water vapour pressure (hPa)\n\nws = wind speed (set to 0 for indoor conditions, and using the SAWS wind speed data for outdoors)\n\nWater vapour was calculated using Equation 2:\n\nAT is given in degrees Celsius (°C) and was calculated for hourly intervals.\n\nAT measurements made inside the shipping container units were considered in relation to thresholds known to be associated with adverse health impacts (Table 1).\n\nThe questionnaire was used to gather information from randomly selected participants (simple random sampling with equal chance of selection) about demographic and socio-economic characteristics, heat-related symptoms ever experienced while occupying the container units, perceptions around heat, and container characteristics. Participants were eligible for the study when they lived in an apartment in the container building or worked in one of the businesses in the container building; they were 18 years old or older; and they consented to participate using an informed consent process.\n\nSample size was determined by the number of fieldworkers (n=3) and the number of fieldwork days available for the study (n=14) together with the required time to conduct the survey (~20 minutes). Some of the participants were not conversant in English so the researchers communicated in other languages such as Zulu, Sotho and Tshwane during data collection. All participants were considered exposed. Responses were anonymised and coded prior to analysis in STATA (version 16) (StataCorp, 2019).12\n\nDescriptive statistics were used to summarize participant characteristics, diurnal and daily patterns of indoor AT and outdoor AT in the shipping containers. Missing data were left as is and no data were inferred. Paired t-tests were used to assess differences between indoor and outdoor AT. A 0.05 level of significance was used for all statistical analysis and data were analysed using R, a language and environment for statistical computing.10 No sensitivity analyses were done.\n\n\nResults\n\nWe were able to analyse temperature and relative humidity data from seven container units and a total of 62 participants (58%) answered the survey.20 Other residents and business owners (n=45) in the building were not available to participate during the study period.\n\nThe study took place during the austral spring (i.e., September) when average ambient temperatures in Johannesburg are ~8°C (minimum) and ~24°C (maximum).13 We successfully measured temperature and relatively humidity in seven container units (three of the iButtons failed during the study campaign). Indoor AT measurements made in the container units displayed similar diurnal patterns with the warmest temperatures occurring in the mid-afternoon (Figure 2). Median indoor AT was 22°C with values ranging from 12°C (observed at 6:00 in unit 9) to 33°C (observed at 15:00 in unit 10). For ambient conditions, median AT was 14°C with values ranging between 6°C to 23°C.\n\nThe whiskers indicate the 95th and 5th percentile, the box indicates the interquartile range, and the middle line is the median.\n\nA comparison of indoor and outdoor AT showed that indoor AT was ~ 7°C higher on average compared to the ambient AT during the study campaign (Figure 3). However, indoor and outdoor conditions were very similar in the afternoon between 13:00 and 17:00 with an AT difference of ~ 1°C. Also, indoor AT fluctuated more than outdoor AT with steep increases observed in the morning and steep decreases recorded in the afternoon.\n\nUnits 2 (residential), 4 (residential), 5 (residential), 6 (residential), 8 (residential), and 10 (business) had insulation installed in the container walls and roof in an attempt to moderate the impacts of ambient temperature on indoor temperature. Unit 9 (business) did not have insulation. Figure 4 illustrates the difference that insulation makes in relation to AT recorded inside the container units with and without insulation. The amplitude of the AT measurements made inside insulated units was smaller than that seen for the non-insulated units for both minimum and maximum indoor AT. The difference in AT for insulated versus non-insulated units ranged between ~2–9°C.\n\nHeat-health risks from AT exposure occurred in all units although there was variation in the number of occurrences that AT measurements exceeded the four symptom bands (Table 2). AT in unit 5 reached the ‘danger’ threshold of between 40 to 51°C once during the study period. In unit 10 there were 13 hourly exceedances of the ‘extreme caution’ threshold of 33–39°C. All units in which AT was measured experienced some exceedances of the ‘caution’ threshold with the greatest occurrences taking place in units 9 (uninsulated) and 10 (insulated).\n\nThe majority of the participants were older than 26 years of age, were male and had completed high school (Table 3). At the time of the survey, the building was 5 years old (built in 2017) and was units were available to rent (and buy) hence most renting occupants had lived in the building for less than 6 months. All surveyed occupants reported that their units had windows and were occupied by one or more people.\n\nAll participants reported that their container units had windows and two-thirds said that these windows, when opened, helped to cool down their units (Table 4). Findings were ambivalent regarding whether participants believed that their units were hot during hot weather and most people opened windows or did nothing during hot weather. Few participants reported experiencing adverse heat-health impacts, except for experiencing headaches (58%) and feeling tired or weak (40%) (Table 5).\n\n* Participants could select multiple responses.\n\n\nDiscussion\n\nThis study has shown the significant variation in indoor temperatures in shipping container units used for living and business purposes in the metropolitan city of Johannesburg. Indoor and outdoor temperatures followed a similar diurnal pattern with far less variation for indoor conditions compared to outdoors. On average, indoor temperatures were consistently warmer than outdoor temperatures and with some non-optimal high temperature exceedances presenting a reason for concern regarding people’s heat-health risks. Laksitoadi and As Syarif14 measured temperatures inside shipping containers repurposed into offices in Badung, Indonesia which has a hot, wet climate. They found that indoor temperatures were on average cooler than outdoor temperatures – differing from our findings here – and that the location of the offices in the building by floor did not influence indoor temperatures. The latter is true for our study findings; there was no consistent pattern in indoor temperatures by storey/level.\n\nAll units in which measurements were made had exceedances of the heat-health risk threshold values related to ‘caution’, ‘extreme caution’, ‘danger’ and ‘extreme danger’. Two container units had the highest frequency of occurrences of temperatures reaching the ‘caution’ (27–32°C) threshold – one unit was insulated and the other was not – that are associated with fatigue possible with prolonged exposure and/or physical activity. This suggests that insulation might not be the sole solution for maintaining consistent temperatures in shipping container units. Alternative means to ensure thermal comfort inside shipping container residential and business units include green/vegetated roofs and outside walls and double-glazing on windows.15 Solar-powered air-conditioning may also be an alternative energy source for indoor cooling, especially in energy-constrained environments such as South Africa. Window shading with awnings or blinds may also help maintain cool indoor temperatures.\n\nSeveral factors influence indoor temperature in dwellings such as the size of the dwelling, number of doors and windows, shading and human behaviour in relation to ventilation and heating/cooling. Shipping containers are a standard size (~14 m2 to 30 m2) – in this apartment block, the open plan studio units were made from containers varying between 28–56 m2 and each had an open landing outdoor space on the ‘inside-facing’ sides of the building. These spaces were less likely to receive natural wind-driven ventilation due to the nature of the balcony location between the two ‘wings’ of the building above the central courtyard (see Figure 1). It will be important for future buildings to consider ventilation and through breezes in their design and construction to ensure indoor temperatures may be reduced, especially in hot climates.\n\nStudy participants were ambivalent regarding whether their units were hot during hot weather; this may be since they had only lived in the unit for around 6 months and had yet to experience the heat of summer between December to February. Few people reported adverse heat-health impacts except for experiencing headaches and feeling tired/weak. Several symptoms and health effects are associated with exposure to non-optimally high indoor temperatures. High indoor temperature exposure has been associated with respiratory, cardiovascular, and mental health effects.16 While our study participants were relatively young, they are also vulnerable to the health impacts of extreme heat. A recent study found stronger associations between days of extreme heat and a higher risk of emergency department visits for any cause, heat-related illness, renal disease, and mental disorders among young and middle aged compared to older adults.16\n\nWhile shipping containers are perceived to be a good alternative for building dwellings, businesses, school classrooms, relief shelters etc. due to their relative low cost, ease of availability, speed to completion during the build, low maintenance, weather-resistant, supposedly relatively low environmental impact (low carbon footprint since at end-of-life at sea/on the road, it is repurposed/upscaled), they may release toxic substances if they had a history of carrying chemicals and they need insulation since the metal frames do not possess insulating properties. The latter is particularly important, especially in light of global warming. South Africa is projected to experience an increase in average ambient temperature between 4–6°C by 2100.17 Furthermore, a heat stress assessment study found that the CBD of the city of Johannesburg, which is where the containers were located, exhibited urban heat island characteristics due to high building densities and sparse vegetation. Thus, residents are at increased risk of heat stress because of exposure to high night and daytime temperatures. Simulations of future local climates estimated increases of up to 5°C, therefore efficient means of maintaining indoor thermal comfort are necessary.18,19 When indoor temperatures inside shipping container units used for living and working mimic outdoor temperatures, and outdoor temperatures are likely to increase, there is reason for concern regarding the health and wellbeing of the occupants. Housing is a constitutional right in South Africa; however, the thermal comfort of the housing requires attention given future climate risks.\n\nThere were several study limitations. We only had ten iButtons available to us which limited our sample size and some of the iButtons failed so data were lost. In future, two iButtons should be placed side-by-side to have a back-up device in the event that one logger fails to prevent data loss. Most of the participants mentioned that they would be out of the city for the holidays so that limited our sample period and sample size. The study period was relatively short (i.e., 14 days) and took place in spring; additional measurements should be made in summer when ambient temperatures are likely higher compared to temperatures in spring. We should have asked business owners working in the business units about the nature of their business to understand whether indoor temperatures were affected by business activities, e.g., the use of hair dryers in a hair salon. We should have also recorded whether the units were north- or south-facing. It would be useful in future studies to conduct physiological measurements of inhabitants of container homes to assess possible heat-health related impacts during hot weather. One may also consider having the participants wear temperature-logging wearables to estimate personal exposure while living and/or working in container-made buildings.\n\n\nConclusion\n\nHousing characteristics influence indoor temperature, and this has an impact on human health and wellbeing. Shipping containers upscaled into living and working units in a modular apartment block is a viable alternative to low-cost housing, however, it is important to consider and factor into the building design indoor temperature stability and by inference, thermal comfort. Given the potential health symptoms and threats associated with non-optimal indoor temperatures, interventions and solutions for thermal comfort must be considered when building residential and business spaces with shipping containers in Africa and elsewhere around the world.",
"appendix": "Data availability\n\nZenodo: iButton and Questionnaire data for container building in Johannesburg, https://doi.org/10.5281/zenodo.8085438. 20\n\nThis project contains the following underlying data:\n\n• Questionnaire data.xlsx (Questionnaire data)\n\n• Temperatures.csv (Temperature data from measurements made in the container rooms)\n\nData are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).\n\nZenodo: STROBE checklist for ‘Container buildings used for residential and business purposes in Johannesburg, South Africa and potential heat-related health risks’, https://doi.org/10.5281/zenodo.8143086. 21\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 thank the owner of the building and the occupants for permitting us to conduct this research. We acknowledge the South African Medical Research Council for the loan of the iButtons.\n\n\nReferences\n\nWorld Health Organization: WHO Housing and Health Guidelines.23 November 2018. Accessed 26 June 2023. Reference Source\n\nStatistics South Africa: General Household Survey.2021. 23 June 2022. Accessed 26 June 2023. Reference Source\n\nLakot Alemdag E, Aydin O: A study of shipping containers as a living space in context of sustainability. ARTiUM. 2015; 3(1): 17–29. Reference Source\n\nZafra RG, Mayo JRM, Villareal PJM, et al.: Structural and thermal performance assessment of shipping container as post-disaster housing in tropical climates. Civil Engineer J. 2021; 7(8): 1437–1458. Publisher Full Text\n\nZhang G, Setunge S, van Elmpt S : Using shipping containers to provide temporary housing in post-disaster recovery: social case studies. Procedia Economic Fin. 2014; 18: 618–625. Publisher Full Text\n\nTheShipsAI: How hot do shipping containers get? Accessed 26 June 2023. Reference Source\n\nElrayies GM: Thermal performance assessment of shipping container architecture in hot and human climates. Int J Advanced Sci Engin Inform Tech. 2017; 7: 1114–1126. Publisher Full Text Reference Source\n\nBidassey-Manilal S, Wright CY, Engelbrecht JC, et al.: Students’ Perceived Heat-Health Symptoms Increased with Warmer Classroom Temperatures. Int J Environ Res Public Health. 2016; 13(6): 566. PubMed Abstract | Publisher Full Text | Free Full Text\n\nNaicker N, Teare J, Balakrishna Y, et al.: Indoor Temperatures in Low Cost Housing in Johannesburg, South Africa. Int J Environ Res Public Health. 2017; 14(11): 1410. PubMed Abstract | Publisher Full Text | Free Full Text\n\nR Core Team: R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2022. Accessed 24 June 2023. Reference Source\n\nSteadman RG: Norms of apparent temperature in Australia. Accessed 23 June 2023. Reference Source\n\nStataCorp: Stata Statistical Software: release 16. College Station, TX: StataCorp LLC.; 2019. Accessed 25 June 2023. Reference Source\n\nClimate Data: Johannesburg Climate (South Africa).2023. Accessed 23 June 2023. Reference Source\n\nLatsitoadi B, As Syarif MH: Refurbished shipping containers as architectural module in Bandung. Advances in Social Science, Education and Humanities Research, Proceedings of the 3rd International Conference on Dwelling Form (IDWELL 2020). 2020; 475: 1–9. Publisher Full Text\n\nTaleb H, Elsebaei M, El-Attar M: Enhancing the sustainability of shipping container homes in a hot arid region: A case study of Aswan in Egypt. Architect Engineer Design Manage. 2019; 15: 459–474. Publisher Full Text\n\nTham S, Thompson R, Landeg O, et al.: Indoor temperature and health: a global systematic review. Public Health. 2020 Feb; 179: 9–17. PubMed Abstract | Publisher Full Text\n\nSun S, Weinberger KR, Nori-Sarma A, et al.: Ambient heat and risks of emergency department visits among adults in the United States: time stratified case crossover study. BMJ. 2021; 375: e065653. PubMed Abstract | Publisher Full Text | Free Full Text\n\nEngelbrecht F, Adegoke J, Bopape M-J, et al.: Projects of rapidly rising surface temperatures over Africa under low mitigation. Environ. Res. Lett. 2015; 10: 085004. Publisher Full Text\n\nSouverijins N, De Ridder K, Veldeman N, et al.: Urban heat in Johannesburg and Ekurhuleni, South Africa: A meter-scale assessment and vulnerability analysis. Urban Clim. 2022; 46: 101331. PubMed Abstract | Publisher Full Text | Free Full Text\n\nWright C: IButton and Questionnaire data for container building in Johannesburg. [Dataset]. Zenodo. 2023. Publisher Full Text\n\nWright C: STROBE checklist for ‘Container buildings used for residential and business purposes in Johannesburg, South Africa and potential heat-related health risks’. Zenodo. 2023. Publisher Full Text"
}
|
[
{
"id": "206274",
"date": "03 Oct 2023",
"name": "Lee Yee Yong",
"expertise": [
"Reviewer Expertise Thermal behaviour in building material",
"thermal comfort study."
],
"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 measured the indoor temperature inside shipping containers comprising a seven-story block of apartments and businesses in Johannesburg, South Africa. This study is good as it could potentially give an important insight into another type of sustainable housing by using containers. However, the effects of temperature are essential due to its material properties on heat transfer, especially in the context of climate change.\nIn the overview of the article, the authors suggest improving the introduction by highlighting the thermal behavior of the material used for the container, as it is also part of the factor contributing to indoor heat storage due to heat transfer. It is also suggested that the author include some thermal properties of the material to support your justification for the impact of heat on temperature. It is important to emphasize the needs and novelty of your contribution towards knowledge as well as promoting the usage of container buildings by overcoming the effects of temperature, especially climate change.\nIn terms of methodology, the authors are advised to include the locality of the instruments within the space of the measurement. The location of the instrument is essential to validating the method of data collection. There are 10 units of containers that have been chosen. Suppose it is believed that there are 10 different surrounding environments for each of the units. The author is suggested to describe the different characteristics of the 10 units to show the temperature variation and fit to the data reporting in the results section. It will have more meaning to reflect the different environmental conditions affecting heat impacts. Besides that, this study incorporated a questionnaire survey and physical measurements. It would be nice if the author could associate the survey findings with the results from the physical measurement, where there is no discussion about it.\nUnder the results section, apparent temperature findings mostly presented the data and lacked critical discussion, which reflected the significant AT difference between the units, e.g., paragraphs 3 and 4 in the results section. More references to support the judgment and the input for different environmental conditions may be helpful in this case.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Partly\n\nAre the conclusions drawn adequately supported by the results? Yes",
"responses": [
{
"c_id": "11107",
"date": "13 Apr 2024",
"name": "Caradee Wright",
"role": "Author Response",
"response": "Reviewer 1 1. This article measured the indoor temperature inside shipping containers comprising a seven-story block of apartments and businesses in Johannesburg, South Africa. This study is good as it could potentially give an important insight into another type of sustainable housing by using containers. However, the effects of temperature are essential due to its material properties on heat transfer, especially in the context of climate change. Response: We thank the reviewer for their comments. 2. In the overview of the article, the authors suggest improving the introduction by highlighting the thermal behavior of the material used for the container, as it is also part of the factor contributing to indoor heat storage due to heat transfer. It is also suggested that the author include some thermal properties of the material to support your justification for the impact of heat on temperature. Response: We have revised the introduction to emphasize the thermal behavior of the container material and its contribution to indoor heat storage. Additionally, we have included relevant thermal properties of the material to support our justification for the impact of heat on temperature. “Shipping containers are made of Corten steel, which possesses the physical properties that make it weldable and rust-resistant.11 Although Corten steel can withstand different weather elements, it also absorbs heat, which can make the interior extremely hot and uncomfortable for humans.10” 3. It is important to emphasize the needs and novelty of your contribution towards knowledge as well as promoting the usage of container buildings by overcoming the effects of temperature, especially climate change. Response: We thank the reviewer for pointing out that we need to emphasize the importance of our study. We have made the following adjustments to the introduction: “The only study analysing temperatures inside shipping containers was of classrooms in Johannesburg, South Africa, which showed temperatures in excess of 40 °C during the summer.15 There have been no studies to characterise thermal comfort conditions by measuring both temperature and humidity inside shipping containers converted into residences or businesses in South Africa. Therefore, we aimed to measure indoor temperature and humidity inside shipping containers comprising a seven-storey block of apartments and businesses in Johannesburg, South Africa.” “The study data may form a foundation for the development of guidelines and regulations required to improve the habitability of converted containers. In addition, these findings are important to inform policy making and health awareness campaigns related to living and working in shipping containers in hot climates.” 4. In terms of methodology, the authors are advised to include the locality of the instruments within the space of the measurement. The location of the instrument is essential to validating the method of data collection. There are 10 units of containers that have been chosen. Suppose it is believed that there are 10 different surrounding environments for each of the units. The author is suggested to describe the different characteristics of the 10 units to show the temperature variation and fit to the data reporting in the results section. It will have more meaning to reflect the different environmental conditions affecting heat impacts. Response: We have rephrased the information on the locality of the instruments within the container space to clarify the suggestion given by the reviewer, thereby specifying the iButton locations for accurate validation of the data collection method. “iButtons were uniformly installed against a cupboard, away from the walls, in all ten containers from September 12 to September 25, 2021.” The characteristics of the 10 selected units have been described in the methodology section, illustrating the variation in environmental conditions affecting heat impacts. “Units 1 to 8 had a similar interior characteristics. The units contain a built-in cupboard and closet, a stove, a fridge, TV stand, couch/chairs and a bed. Unit 9, which was the salon had a wall-to-wall table with 7 chairs, a cabinet where they store their tools, and some tools were, displayed on the table. The office contained a table, four chairs and a small free-standing cabinet.” 4. Besides that, this study incorporated a questionnaire survey and physical measurements. It would be nice if the author could associate the survey findings with the results from the physical measurement, where there is no discussion about it. Response: We thank the reviewer for their insightful feedback and suggestion to link physical measurements to survey findings. We appreciate their thoroughness in reviewing our work. Unfortunately, the request cannot be fulfilled due to logistical constraints as this data cannot be linked. 5. Under the results section, apparent temperature findings mostly presented the data and lacked critical discussion, which reflected the significant AT difference between the units, e.g., paragraphs 3 and 4 in the results section. More references to support the judgment and the input for different environmental conditions may be helpful in this case. Response: You rightly pointed out that paragraphs 3 and 4 in the results section primarily present the data without critical discussion. However, It is a common practice to maintain a clear distinction between the results and discussion sections to enhance the clarity and organization of the manuscript. The results section is intended to present the findings without interpretation, allowing readers to objectively evaluate the data. On the other hand, the discussion section serves the purpose of interpreting the results, comparing them with existing literature, and providing a broader context for the study. By adhering to this separation, we aim to ensure a logical flow and readability of the manuscript. Therefore, we propose that the critical discussion of the apparent temperature findings, along with additional references to support the judgment and insights on different environmental conditions, be appropriately addressed in the dedicated discussion section. We are committed to enhancing the manuscript based on your valuable suggestions and we have added additional insights in the discussion section. 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? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Yes"
}
]
},
{
"id": "206272",
"date": "06 Oct 2023",
"name": "Sarah Roffe",
"expertise": [
"Reviewer Expertise I am a climatologist. Within this field",
"and relevant to this study",
"I focus on outdoor thermal comfort (stress) as one aspect of my 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\nThis article, assessing indoor (and outdoor) thermal comfort in container buildings, is very relevant in the context of South Africa's housing crisis and the need to explore alternative, cheaper housing options while bearing in mind thermal health-related risks associated with housing options. Academically this article provides a good contribution to the limited literature regarding thermal comfort (stress) in a South African context, and it is important to inform South African developers (housing and non-housing developers). Thus, there is merit in its publication. However, before publication I have minor (perhaps even major in some instances) suggestions that I believe can significantly improve the article content and presentation:\nCheck the author affiliations - I think no 1 & 2 should be the same.\n\nAbstract, background - The title refers to container buildings for housing and business yet the background is more focused on housing. Perhaps you could adjust the wording to 'Buildings (for housing and business purposes) that can protect humans...'\n\nAbstract, method - To contextualise the results and their repetitiveness, add in the sampling period duration.\n\nAbstract, results - When noting the AT range it will be valuable to provide the AT classification as well so that a reader can contextualise the classified body effect.\n\nAbstract, results - In your sample, there was only one non-insulated unit. Compared to the insulated units, there was certainly a difference, but care must be taken to highlight this caveat.\n\nAbstract, results - n = ? for the feeling tired or weak statistic.\n\nAbstract, conclusion - Although Figure 4 shows that on average insulated units have lower variation in AT (compared to the one non-insulated unit), Table 2 results suggest that the recommendation of insulated units should be assessed further (compare results for units 5, 9 [NI] and 10). This certainly suggests that above insulation, there may be other factors influencing the AT values, thus I would rather note that tentatively, the results suggest that units should be insulated. And in the conclusion I would make a note that further research on this topic is very much needed. You could also note that air conditioning is needed - of course as you highlighted, solar air conditioning would be most viable given the current electricity crisis in South Africa.\n\nAbstract, conclusion - Perhaps this is an addition for the conclusion in the article... The value of your study in educating those building these container buildings should also be highlighted as it is largely their building specifications that will determine whether the building will be suitable in light of thermal health related risks.\n\nIntroduction - This section only focuses on the consideration of housing, yet many people spend a large proportion of their time in a business context in buildings. Provide some consideration thereof in the introduction.\n\nIntroduction - First word improved is perhaps misleading. Improved compared to? Perhaps use good as an alternative word.\n\nIntroduction - Add bracket after '...(the remaining 5% remains unknown\n\nIntroduction - First sentence of second paragraph needs a reference. Consider checking whether references are included where needed throughout the manuscript.\n\nMethods, Study design - Provide further detail of the STROBE reporting guideline for a reader who does not know about it.\n\nMethods, Study design - Consider adding in a study site map to show the location of the container units, especially in relation to the SAWS weather station used.\n\nMethods, Study design - Why was the period of 12-25 Sep 2021 used for sampling? I would provide justification in text.\n\nMethods, Temperature measurements - The heading of this section is misleading as you did not only record temperatures. Instead title the section Meteorological measurements?\n\nMethods, Temperature measurements - More information is required for the iButtons loggers. How often do they provide measurements?\n\nMethods, Temperature measurements - More information is required for the SAWS weather station. Which weather station was this? How far is it from the container building? etc. This is why I suggested a study site map - perhaps consider adding landuse/cover and elevation to give the reader context on how representative this station is.\n\nMethods, Apparent temperature calculations and heat-health risks - Why have you considered the apparent temperature method? Provide some justification, especially because the metric used to assess thermal comfort can strongly influence results (see: Simpson, C.H., Brousse, O., Ebi, K.L. and Heaviside, C., 2023. Commonly used indices disagree about the effect of moisture on heat stress. npj Climate and Atmospheric Science, 6(1), p.78.). I am not suggesting to change the method, but I am suggesting you acknowledge this consideration of metrics and their potential influence on results, especially in your final discussion paragraph.\n\nMethods, Survey questionnaire - All participants were considered exposed. Exposed to what? Be more specific.\n\nMethods, Statistical analysis - Provide detail on how much data were missing. A supplementary table should suffice.\n\nMethods, Statistical analysis - You report on using the paired t-test, but in the results you do not show any results thereof. Either add these results or omit noting that you used the paired t-test.\n\nResults - The first paragraph provides information more suited to the methods. I would incorporate this information in the methods.\n\nResults, Apparent temperature findings - Avoid referral to ambient temperature in the context of your work. Rather refer to indoor or outdoor temperature as ambient temperature refers to the temperature of the immediate surroundings which can be indoor or outdoor.\n\nResults, Apparent temperature findings - Over what period (i.e. years) and at what resolution (i.e. daily or monthly) are the September temperatures you refer to, and is this from the SAWS station you used? Take care not to omit such important information.\n\nResults, Apparent temperature findings - 'Indoor AT measurements made in the container units displayed similar diurnal patterns with the warmest temperatures occurring in the mid-afternoon (Figure 2).' Your figure does not show this?\n\nResults, Apparent temperature findings - Your figure captions are slightly incorrect. You cannot refer to a trend with only 14 days of data. A trend in a climatological context is a measurement of 'change' over at least a 30 year period. You are only showing average diurnal variation in AT for figure 2-4.\n\nResults, Apparent temperature findings - Provide more reference to the figures in your results as it not always clear as to which figure you are referring to.\n\nResults, Apparent temperature findings - At the end of the second paragraph, you say that indoor AT fluctuated more than outdoor AT. This is not true according to Figure 3.\n\nResults, Apparent temperature findings - Figure 2 could be be improved on. I would ideally indicate which units were insulated and which unit was not insulated, and for better comparability of AT, it is necessary to use the same y-axis range. Also, consider providing a straight lines from the y-axis to indicate the different AT thresholds for Table 1. This will provide more context to your results. This last suggestion also applies for figure 3.\n\nResults, Apparent temperature findings - You note that AT for insulated vs non-insulated differed by ~2-9 degrees C. Were the values statistically different (i.e. what are the t-test results)?\n\nResults, Apparent temperature findings - You could add an indication of whether the unit was insulated or not for table 2 to help interpret the results of this table. Also, as previously mentioned, it does not provide compelling evidence that insulated units are better, especially since your sample size is small with only one unit that is not insulated.\n\nResults, Questionnaire findings - The second sentence should be reworded.\n\nResults overall - No t-test results are reported despite mention in the methods.\n\nResults overall - consider adding more reporting on the results to strengthen this section.\n\nDiscussion - 'This study has shown the significant variation in indoor temperatures in shipping container units used for living and business purposes in the metropolitan city of Johannesburg.' This sentence is misleading. You have used significant in an incorrect manner. This is a statistical term and should only be used if there is statistical backing for which there is not in this paper. Consider rewording this sentence to more appropriately align with what you have truly shown in your study.\n\nDiscussion - 'On average, indoor temperatures were consistently warmer than outdoor temperatures...' How much warmer? A sentence like this should always be backed up by numerical estimates.\n\nDiscussion - 'All units in which measurements were made had exceedances of the heat-health risk threshold values related to ‘caution’, ‘extreme caution’, ‘danger’ and ‘extreme danger’.' According to Table 2 and Figure 2, this sentence is misleading and perhaps even incorrect. If I am interpreting the results correctly, all units recorded caution levels, but only 3 recorded levels above this?\n\nDiscussion - 'Two container units had the highest frequency of occurrences of temperatures reaching the ‘caution’ (27–32°C) threshold – one unit was insulated and the other was not – that are associated with fatigue possible with prolonged exposure and/or physical activity'. This sentence also seems to be misleading and perhaps incorrect.\n\nDiscussion - 'This suggests that insulation might not be the sole solution for maintaining consistent temperatures in shipping container units.' But you suggest insulation in the abstract? Some of your statements are contradictory.\n\nDiscussion - When referring to results in the discussion, it is good practice to refer to the Table or Figure showing the results.\n\nDiscussion - Third paragraph first sentence needs a reference. In fact, I recommend more actively referencing in your work.\n\nDiscussion - 'South Africa is projected to experience an increase in average ambient temperature between 4–6°C by 2100.17 ' This should be reference 18.\n\nDiscussion - 'Furthermore, a heat stress assessment study found that the CBD of the city of Johannesburg, which is where the containers were located, exhibited urban heat island characteristics due to high building densities and sparse vegetation. ' This sentence needs a reference.\n\nDiscussion - You suggest two iButtons in case one fails. This could also be useful for comparability to determine accuracy of the readings.\n\nConclusion - You study opens doors for much more research to be undertaken. I think it is important that you highlight this so that a reader can better contextualise your results and also so they can consider how representative your results are. Important for this is assessing seasonality and also taking readings over multiple years to account for variability.\n\nIs the work clearly and accurately presented and does it cite the current literature? Yes\n\nIs the study design appropriate and is the work technically sound? Yes\n\nAre sufficient details of methods and analysis provided to allow replication by others? Yes\n\nIf applicable, is the statistical analysis and its interpretation appropriate?\nPartly\n\nAre all the source data underlying the results available to ensure full reproducibility? Yes\n\nAre the conclusions drawn adequately supported by the results? Partly",
"responses": [
{
"c_id": "11108",
"date": "13 Apr 2024",
"name": "Caradee Wright",
"role": "Author Response",
"response": "Reviewer 2 APPROVED WITH RESERVATIONS This article, assessing indoor (and outdoor) thermal comfort in container buildings, is very relevant in the context of South Africa's housing crisis and the need to explore alternative, cheaper housing options while bearing in mind thermal health-related risks associated with housing options. Academically this article provides a good contribution to the limited literature regarding thermal comfort (stress) in a South African context, and it is important to inform South African developers (housing and non-housing developers). Thus, there is merit in its publication. However, before publication I have minor (perhaps even major in some instances) suggestions that I believe can significantly improve the article content and presentation: Check the author affiliations - I think no 1 & 2 should be the same. Response: The author’s affiliations are accurately reported and comprise of two different government departments that the author has affiliations with. Abstract, background - The title refers to container buildings for housing and business yet the background is more focused on housing. Perhaps you could adjust the wording to 'Buildings (for housing and business purposes) that can protect humans...' Response: We have adjusted the introduction to better reflect the focus on both housing and business aspects of container buildings as follows: “Properly designed and constructed residential, business and public service spaces can help prevent disease, reduce poverty, and increase quality of life.1,2 Adequate, safe housing and working environments are essential in the current global context of urbanisation, ageing populations, and climate change.1 In South Africa, around 80% of the population of around ~60 million people live in formal dwellings, 11% live in informal dwellings such as shacks, 4% live in traditional dwellings and the other 5% is unknown.3 Government-provided, formal low-cost housing has failed to address the growing informal housing problem in South Africa.4 Recently, initiatives by developers have increased the use of shipping containers to provide for South Africans who earn very little. As low-cost housing solutions, several shipping containers have been combined into a single storey or stacked to make a multi-storey block of apartments. To serve poorer communities, shipping containers have been used as clinics as well as “spaza shops” to sell essential items in townships.5,6 ” Abstract, method - To contextualise the results and their repetitiveness, add in the sampling period duration. Response: We have added the sampling period to the abstract: “…comprising a seven-storey block of apartments and businesses in Johannesburg, South Africa for 14 days.” Abstract, results - When noting the AT range it will be valuable to provide the AT classification as well so that a reader can contextualise the classified body effect. Response: We thank the reviewer for their comment. The definition of AT is already present in the abstract in a manner concise enough to adhere to the abstract word count as follows: “Median indoor apparent temperature (AT) (a combination of temperature and relative humidity)” Abstract, results - In your sample, there was only one non-insulated unit. Compared to the insulated units, there was certainly a difference, but care must be taken to highlight this caveat. Response: We changed the wording to reflect that there was one uninsulated unit as follows: “than the uninsulated unit” Abstract, results - n = ? for the feeling tired or weak statistic. Response: The “n= 62” has been removed from “experiencing headaches,” thus ensuring uniformity in the reporting of results in the abstract. Abstract, conclusion - Although Figure 4 shows that on average insulated units have lower variation in AT (compared to the one non-insulated unit), Table 2 results suggest that the recommendation of insulated units should be assessed further (compare results for units 5, 9 and 10). This certainly suggests that above insulation, there may be other factors influencing the AT values, thus I would rather note that tentatively, the results suggest that units should be insulated. And in the conclusion I would make a note that further research on this topic is very much needed. You could also note that air conditioning is needed - of course as you highlighted, solar air conditioning would be most viable given the current electricity crisis in South Africa. Response: The conclusion within the abstract has been edited as follows: “Residents, tenants, or business owners using shipping containers should consider insulation installation and adequate windows/air conditioning for ventilation, especially in hot climates. Further research and awareness regarding heat-health risks of living or working in these spaces is needed.” Abstract, conclusion - Perhaps this is an addition for the conclusion in the article... The value of your study in educating those building these container buildings should also be highlighted as it is largely their building specifications that will determine whether the building will be suitable in light of thermal health related risks. Response: We thank the reviewer for their comment. We have addressed this concern in the conclusion as follows: “The findings of future studies that analyse optimisation of thermal comfort in shipping containers should be used to advocate for and educate people who oversee the adaptation of shipping containers for either residential or business uses.” Introduction - This section only focuses on the consideration of housing, yet many people spend a large proportion of their time in a business context in buildings. Provide some consideration thereof in the introduction. Response: The introduction has been edited to reflect this concern as follows: “Properly designed and constructed residential, business and public service spaces can help prevent disease, reduce poverty, and increase quality of life.1,2 Adequate, safe housing and working environments are essential in the current global context of urbanisation, ageing populations, and climate change.1 In South Africa, around 80% of the population of around ~60 million people live in formal dwellings, 11% live in informal dwellings such as shacks, 4% live in traditional dwellings and the other 5% is unknown.3 Government-provided, formal low-cost housing has failed to address the growing informal housing problem in South Africa.4 Recently, initiatives by developers have increased the use of shipping containers to provide for South Africans who earn very little. As low-cost housing solutions, several shipping containers have been combined into a single storey or stacked to make a multi-storey block of apartments. To serve poorer communities, shipping containers have been used as clinics as well as “spaza shops” to sell essential items in townships.5,6.” Introduction - First word improved is perhaps misleading. Improved compared to? Perhaps use good as an alternative word. Response: The wording of the first sentence of the introduction has been changed as follows: “Improved housing conditions” was changed to “Properly designed and constructed residential, business and public service spaces” Introduction - Add bracket after '.(the remaining 5% remains unknown Response: We thank for reviewer for spotting this error. This error has been corrected in the document. Introduction - First sentence of second paragraph needs a reference. Consider checking whether references are included where needed throughout the manuscript. Response: We thank the reviewer for their insight. We have added a suitable reference to the sentence. Methods, Study design - Provide further detail of the STROBE reporting guideline for a reader who does not know about it. Response: Further clarity has been added on the value of the using STROBE guidelines to enhance the quality of observational study data: “Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines were used to plan and execute this study. The STROBE guidelines ensure the highest quality of observational study data and consists of 22 checklist items that should be addressed in a study.16” Methods, Study design - Consider adding in a study site map to show the location of the container units, especially in relation to the SAWS weather station used. Response: Thank you for your insightful feedback and suggestion to include a study site map showcasing the container units' location in relation to the SAWS weather station. We have included a study site map and it is now Figure 1 in the revised manuscript. Methods, Study design - Why was the period of 12-25 Sep 2021 used for sampling? I would provide justification in text. Response: A sentence has been added to justify the sampling period: “The sampling took place in September because it is spring time in South Africa, and high temperatures were recorded in previous years during this month.” Methods, Temperature measurements - The heading of this section is misleading as you did not only record temperatures. Instead title the section Meteorological measurements? Response: The heading has been changed to “Meteorological measurements” Methods, Temperature measurements - More information is required for the iButtons loggers. How often do they provide measurements? Response: The frequency of measurements from the iButtons has been added to the description: “iButtons are small, portable sensors that record hourly temperature and relative humidity” Methods, Temperature measurements - More information is required for the SAWS weather station. Which weather station was this? How far is it from the container building? etc. This is why I suggested a study site map - perhaps consider adding landuse/cover and elevation to give the reader context on how representative this station is. Response: We thank the reviewer for this comment. The location of the weather station is now given in Figure 1 of the revised manuscript. Methods, Apparent temperature calculations and heat-health risks - Why have you considered the apparent temperature method? Provide some justification, especially because the metric used to assess thermal comfort can strongly influence results (see: Simpson, C.H., Brousse, O., Ebi, K.L. and Heaviside, C., 2023. Commonly used indices disagree about the effect of moisture on heat stress. npj Climate and Atmospheric Science, 6(1), p.78.). I am not suggesting to change the method, but I am suggesting you acknowledge this consideration of metrics and their potential influence on results, especially in your final discussion paragraph. Response: We would like to clarify that the paper by Simpson et al. (2023) raises important considerations about the potential influence of radiation and wind on the calculation of real feel temperature using different metrics on heat stress assessment. The paper emphasizes that when calculating indoor ambient temperature, wind and radiation do not need to be considered. Thus, we used a suitable equation to calculate indoor and outdoor real feel temperature. Nevertheless, we acknowledge the significance of addressing the potential impact of the chosen metric on our results. Here are some quotes from other articles that used AT to calculate real feel temperatures in indoor environments: First citation: Naicker, N., Teare, J., Balakrishna, Y., Wright, C. Y., & Mathee, A. (2017). Indoor Temperatures in Low Cost Housing in Johannesburg, South Africa. International Journal of Environmental Research and Public Health, 14(11). https://doi.org/10.3390/ijerph14111410 “Apparent temperature is an indicator of thermal sensation, can be used in indoor settings [28] and has been used before when considering the relationship between heat and thermal comfort [29,30].” 28. Nguyen, J.L.; Schwartz, J.; Dockery, D.W. The relationship between indoor and outdoor temperature, relative humidity, and absolute humidity. Indoor Air 2014, 24, 103–112. 29. Baccini, M.; Biggeri, A.; Accetta, G.; Kosatsky, T.; Katsouyanni, K.; Analitis, A.; Anderson, H.R.; Bisanti, L.; D’Ippoliti, D.; Danova, J.; et al. Heat effects on mortality in 15 European cities. Epidemiology 2008, 19, 711–719. 30. Bell, M.L.; O’Neill, M.S.; Ranjit, N.; Borja-Aburto, V.H.; Cifuentes, L.A.; Gouveia, N.C. Vulnerability to heat-related mortality in Latin America: A case-crossover study in Sao Paulo, Brazil, Santiago, Chile and Mexico City, Mexico. Int. J. Epidemiol. 2008, 37, 796–804. Second citation: Kapwata, T., Gebreslasie, M. T., Mathee, A., & Wright, C. Y. (2018). Current and Potential Future Seasonal Trends of Indoor Dwelling Temperature and Likely Health Risks in Rural Southern Africa. International Journal of Environmental Research and Public Health, 15(5). https://doi.org/10.3390/ijerph15050952 “AT is an adjustment to the ambient temperature based on the level of relative humidity and it is deemed a measure of how humans actually perceive or feel temperature. AT is the most frequently used indicator of probable human physical reaction to weather conditions and several studies have used AT to examine the association between health and high temperature [46–49].” 46. Garland, R.M.; Matooane, M.; Engelbrecht, F.A.; Bopape, M.J.M.; Landman, W.A.; Naidoo, M.; Merwe, J.V.D.; Wright, C.Y. Regional projections of extreme apparent temperature days in Africa and the related potential risk to human health. Int. J. Environ. Res. Public Health 2015, 12, 12577–12604. 47. Harlan, S.L.; Brazel, A.J.; Prashad, L.; Stefanov, W.L.; Larsen, L. Neighborhood microclimates and vulnerability to heat stress. Soc. Sci. Med. 2006, 63, 2847–2863. 48. Watts, J.D.; Kalkstein, L.S. The development of a warm-weather relative stress index for environmental applications. J. Appl. Meteorol. 2004, 43, 503–513. [CrossRef] 49. Baccini, M.; Biggeri, A.; Accetta, G.; Kosatsky, T.; Katsouyanni, K.; Analitis, A.; Anderson, H.R.; Bisanti, L.; D’ippoliti, D.; Danova, J.; et al. Heat effects on mortality in 15 European cities. Epidemiology 2008, 19, 711–719. Methods, Survey questionnaire - All participants were considered exposed. Exposed to what? Be more specific. Response: We apologize for the ambiguity in the statement and have removed the sentence. Methods, Statistical analysis - Provide detail on how much data were missing. A supplementary table should suffice. Response: We thank the reviewer for addressing this concern. By acknowledging and appropriately handling missing data, we aim to uphold the integrity of our study and contribute to the broader scientific discourse with accurate and reliable results. To address the issue of missing data we have mentioned that 50% of the data were missing. Methods, Statistical analysis - You report on using the paired t-test, but in the results you do not show any results thereof. Either add these results or omit noting that you used the paired t-test. Response: We thank the reviewer for this comment and after deliberations, we realised that the t-test was not performed due to small sample size and was not removed from the original draft of the manuscript. We apologize for this oversight, and we have now removed the mention of a t-test from the methods. Results - The first paragraph provides information more suited to the methods. I would incorporate this information in the methods. Response: This paragraph was rephrased and added to the methods section under the subheading “Survey questionnaire”: “We administered a short survey questionnaire to occupants of the units after obtaining their informed consent.” “A total of 62 participants (58%) answered the survey. Other residents and business owners (n=45) in the building were not available to participate during the study period.” Results, Apparent temperature findings - Avoid referral to ambient temperature in the context of your work. Rather refer to indoor or outdoor temperature as ambient temperature refers to the temperature of the immediate surroundings which can be indoor or outdoor. Response: We apologize for the ambiguity in the use of the word “ambient” and we have corrected this throughout the manuscript. Results, Apparent temperature findings - Over what period (i.e. years) and at what resolution (i.e. daily or monthly) are the September temperatures you refer to, and is this from the SAWS station you used? Take care not to omit such important information. Response: We thank the reviewer for this query and we would like to clarify that the SAWS data was within the same time frame as the iButtons measurements comparing the outdoor and indoor temperature during the month of September. Thus, the information was not omitted, and the period of the study was given in the methods section. We have clarified this within the manuscript in the methods section as follows under “Meteorological measurements”: “Meteorological data within the study period (12 September to 25 September 2021) were provided at 10-minute intervals which were converted to hourly interval calculations.” Results, Apparent temperature findings - Indoor AT measurements made in the container units displayed similar diurnal patterns with the warmest temperatures occurring in the mid-afternoon (Figure 2). Your figure does not show this? Response: Upon careful re-evaluation of Figure 2, the figure illustrates the diurnal patterns of indoor apparent temperature measurements, with the warmest temperatures observed in the mid-afternoon. Results, Apparent temperature findings - Your figure captions are slightly incorrect. You cannot refer to a trend with only 14 days of data. A trend in a climatological context is a measurement of 'change' over at least a 30 year period. You are only showing average diurnal variation in AT for figure 2-4. Response: To address your concern and ensure clarity, we modified the captions to use the term \"changes,\" which better aligns with the temporal scope of our study. Results, Apparent temperature findings - Provide more reference to the figures in your results as it not always clear as to which figure you are referring to. Response: We have carefully considered your suggestion and upon re-evaluation of the results section we have noted the following: We have explicit references to the relevant figures in the text. We have detailed figure citations, ensuring that readers can easily identify and cross-reference the information presented in the text with the corresponding figures. We have figure captions to provide clear descriptions of the key findings presented in each figure. We believe that these elements significantly provide an alignment between the narrative in the Results section and the corresponding figures, thereby facilitating a seamless understanding of our findings. We hope that these characteristics of our results section effectively address your concerns so that you are assured that we have provided an overall seamless reading experience for our audience. Results, Apparent temperature findings - At the end of the second paragraph, you say that indoor AT fluctuated more than outdoor AT. This is not true according to Figure 3. Response: We apologise for the incorrect use of the term “fluctuated” and we have edited the statement to be more accurate as follows: \"Indoor AT showed greater variability compared to outdoor AT, with steep increases observed in the morning and sharp declines in the afternoon.\" Results, Apparent temperature findings - Figure 2 could be improved on. I would ideally indicate which units were insulated and which unit was not insulated, and for better comparability of AT, it is necessary to use the same y-axis range. Also, consider providing a straight lines from the y-axis to indicate the different AT thresholds for Table 1. This will provide more context to your results. This last suggestion also applies for figure 3. Response: We have revised figure 2 so that all plots have the same y-axis, however, we prefer not to add threshold lines as the graphs will become very cluttered. Results, Apparent temperature findings - You note that AT for insulated vs non-insulated differed by ~2-9 degrees C. Were the values statistically different (i.e. what are the t-test results)? Response: We thank the reviewer for this comment and after deliberations, we realised that the t-test was not performed due to small sample size and was not removed from the original draft of the manuscript. We apologize for this oversight, and we have now removed the mention of a t-test from the methods. Statistical significance could not be elaborated. Results, Apparent temperature findings - You could add an indication of whether the unit was insulated or not for table 2 to help interpret the results of this table. Also, as previously mentioned, it does not provide compelling evidence that insulated units are better, especially since your sample size is small with only one unit that is not insulated. Response: An indication of which units were insulated and which were uninsulated were added as a footnote to Table 2. Regarding the comment on whether insulation was better or not, this study did not aim to elucidate the affect of insulation on shipping containers and the uninsulated container was not a control that was measured against the insulated shipping containers. We may have confused the reviewer by adding a paragraph addressing insulation of shipping containers in the introduction. Therefore, we have moved this paragraph addressing the effects on insulation on thermal comfort to the discussion. Results, Questionnaire findings - The second sentence should be reworded. Response: We thank the reviewer for this suggestion. The sentence has been edited as follows: “At the time of the survey, the shipping container structure was 5 years old, having been assembled in 2017, when units were available to rent or purchase. All participants of this study were utilizing the containers for less than 6 months. All surveyed participants reported that their units had windows and were occupied by one or more people.” Results overall - No t-test results are reported despite mention in the methods. Response: We thank the reviewer for this comment and after deliberations, we realised that the t-test was not performed due to small sample size and was not removed from the original draft of the manuscript. We apologize for this oversight, and we have now removed the mention of a t-test from the methods. Results overall - consider adding more reporting on the results to strengthen this section. Response: We sincerely appreciate the thoughtful feedback, and we have diligently incorporated these valuable suggestions into the results section. In response to the specific comment regarding the need for additional reporting, we have enhanced the comprehensiveness of our results presentation by meticulously addressing each and every comment and incorporating pertinent adjustments. Discussion - 'This study has shown the significant variation in indoor temperatures in shipping container units used for living and business purposes in the metropolitan city of Johannesburg.' This sentence is misleading. You have used significant in an incorrect manner. This is a statistical term and should only be used if there is statistical backing for which there is not in this paper. Consider rewording this sentence to more appropriately align with what you have truly shown in your study. Response: We apologize for the incorrect use of the word “significant” and we have rephrased the sentence as follows: “This study has successfully clarified the low indoor thermal comfort characteristics of shipping container units used for living and business purposes in a hot and humid environment in the metropolitan city of Johannesburg.” Discussion - 'On average, indoor temperatures were consistently warmer than outdoor temperatures...' How much warmer? A sentence like this should always be backed up by numerical estimates. Response: The numerical reference was added to the sentence: “Indoor temperatures were consistently warmer than outdoor temperatures (~ 7°C higher on average) and with some non-optimal high temperature exceedances presenting a reason for concern regarding people’s heat-health risks.” Discussion - 'All units in which measurements were made had exceedances of the heat-health risk threshold values related to ‘caution’, ‘extreme caution’, ‘danger’ and ‘extreme danger’.' According to Table 2 and Figure 2, this sentence is misleading and perhaps even incorrect. If I am interpreting the results correctly, all units recorded caution levels, but only 3 recorded levels above this? Response: We thank the reviewer for this comment. We have edited the sentences as follows: “All units in which measurements were made exceeded heat-health risk threshold values related to ‘caution’. Three units exceeded the threshold values related to ‘extreme caution’ of 33-39 ℃. One unit exceeded the threshold values related to ‘danger’ of 40-51 ℃.” Discussion - 'Two container units had the highest frequency of occurrences of temperatures reaching the ‘caution’ (27–32°C) threshold – one unit was insulated and the other was not – that are associated with fatigue possible with prolonged exposure and/or physical activity'. This sentence also seems to be misleading and perhaps incorrect. Response: We thank the reviewer for their comments and we have edited the statement as follows: “Two container units, one insulated and the other not had the highest frequency of temperature occurrences surpassing the ‘caution’ (27 – 32°C) threshold. These temperatures are associated with fatigue that is equivalent to prolonged heat exposure and / or physical activity.” Discussion - 'This suggests that insulation might not be the sole solution for maintaining consistent temperatures in shipping container units.' But you suggest insulation in the abstract? Some of your statements are contradictory. Response: We apologize for the confusion caused by discussing insulation of shipping containers in the introduction. We have moved this paragraph to the discussion. Discussion - When referring to results in the discussion, it is good practice to refer to the Table or Figure showing the results. Response: We thank the reviewer for their comment. After careful consideration, we would like to provide our rationale for not explicitly referring to specific tables and figures in the discussion section. While we understand the common practice of referencing tables and figures to enhance clarity, we have opted for a more narrative approach in our discussion to maintain a cohesive and flowing narrative. We aimed to present our findings in a manner that allows readers to follow the logical progression of our arguments without constant references to specific data visuals, that has already been done in the results section. However, to address your concern, we have ensured that key results are appropriately highlighted in the text, providing a clear link between our discussion points and the corresponding data in tables and figures. We believe this approach maintains readability while still allowing for a comprehensive understanding of our results. We hope this explanation aligns with the standards of the journal, and we are open to further suggestions or modifications if needed. Discussion - Third paragraph first sentence needs a reference. In fact, I recommend more actively referencing in your work. Response: We thank the reviewer for their comment on referencing. We acknowledge the importance of providing proper citations to support our statements and have addressed this concern by incorporating additional references throughout our work. Discussion - 'South Africa is projected to experience an increase in average ambient temperature between 4–6°C by 2100.17 ' This should be reference 18. Response: We thank the reviewer for pointing out this error. We have redone all references in light of the extensive changes to the manuscript and have taken precautions to ensure that all referencing is accurate. Discussion - 'Furthermore, a heat stress assessment study found that the CBD of the city of Johannesburg, which is where the containers were located, exhibited urban heat island characteristics due to high building densities and sparse vegetation.' This sentence needs a reference. Response: We thank the reviewer for their comment. We have added the following reference: Hardy C, Nel A. Data and techniques for studying the urban heat island effect in Johannesburg. ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences. XL-7/W3. 203-206. 10.5194/isprsarchives-XL-7-W3-203-2015. 2015. Discussion - You suggest two iButtons in case one fails. This could also be useful for comparability to determine accuracy of the readings. Response: We thank the reviewer for their insight. We have added this to the conclusions: “In future, two iButtons should be placed side-by-side to have a back-up device in the event that one logger fails to prevent data loss and to increase the accuracy and variation between the readings.” Conclusion - You study opens doors for much more research to be undertaken. I think it is important that you highlight this so that a reader can better contextualise your results and also so they can consider how representative your results are. Important for this is assessing seasonality and also taking readings over multiple years to account for variability. Response: We thank the reviewer for their insight. We have added a paragraph on future studies to the conclusions. “Given the projected extreme outdoor temperatures (both heat and cold) due to climate change, it is imperative to devise strategies to enhance indoor thermal comfort. This is particularly important for low- and middle-income countries, ensuring the well-being of those forced to consider cheaper building options. The information gleaned from this study can be used to conceptualise future research to solve the thermal comfort limitations of shipping containers. Characterising measures to ensure thermal comfort inside shipping container residential and business units is warranted. Solutions such as green or vegetated roofs, exterior wall insulation options, double-glazing on windows,21 and solar-powered air-conditioning could be further explored and optimized. Building on insights from similar studies in different climates, researchers can delve deeper into the performance of various insulation materials, considering factors such as cost-effectiveness and sustainability. The influence of building design is especially interesting, particularly ventilation through breezes and the direction of buildings. Indoor temperatures should be a focal point for architects and urban planners aiming to create climate-resilient structures. Future research could also extend beyond temperature measurements to include physiological assessments of inhabitants for personalized exposure estimates, providing a more holistic understanding of heat-health impacts. Finally, addressing study limitations by increasing sample size, incorporating backup devices, and extending data collection periods to both summer and winter would strengthen the reliability and applicability of future research in this domain.” 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? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly References 1. Simpson C, Brousse O, Ebi K, Heaviside C: Commonly used indices disagree about the effect of moisture on heat stress. npj Climate and Atmospheric Science. 2023; 6 (1). Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise I am a climatologist. Within this field, and relevant to this study, I focus on outdoor thermal comfort (stress) as one aspect of my research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above."
}
]
}
] | 1
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https://f1000research.com/articles/12-929
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